Patient & Survivor Care

Before the onslaught of COVID-19, researchers at the Fred Hutchinson Cancer Research Center in Seattle had another infectious disease worry: an “unprecedented” outbreak of measles.

“In 2019, we saw the most measles cases in any year since the 1990s,” said Sara Marquis, MPH, a clinical research coordinator at the center. The worry, she says, was that various oncology treatments, such as bone marrow transplantations and assorted biologics, “may leave cancer patients severely immunosuppressed” and thus vulnerable to infectious diseases.

Measles-related illness is typically not severe but can lead to pneumonia, deafness, and death, even in immunocompetent people, Ms. Marquis added.

So in 2019, a team at Fred Hutchinson initiated a study to get a sense of immunity to measles among patients with cancer.

They now report that of a group of 900-plus patients, 25% lacked protective antibodies for measles. That’s “significantly more” than the general population, in which about 8% of people lack these antibodies, Ms. Marquis said.

The study, published online in JAMA Network Open, also found that 38% lacked protection against the less-worrisome infectious disease of mumps, which is more than the 13% found in the general population.

“The scary thing about measles is that it is one of the most contagious diseases known,” Ms. Marquis told this news organization, adding that it is about twice as contagious as the COVID-19 Delta variant.

And it’s not just in the state of Washington. “We’re seeing it more and more in the community,” as various outbreaks continue to happen, she said.

“Deficits in protective antibodies underscore patients’ increased risk during outbreaks and emphasize the need for community-based efforts to increase herd immunity to protect this population,” the study authors conclude.

In short, administration of the measles-mumps-rubella (MMR) vaccine, introduced in 1963, must continue universally, they said

“We’ve had so many incredible advances in cancer treatment in recent years. … it would be devastating to see something like measles, which is a vaccine-preventable disease, come through and negate those efforts,” said study coauthor Elizabeth Krantz, MS, a biostatistician at Fred Hutchinson.

The health care teams and family caregivers of patients with cancer should also make sure they are vaccinated, said Ms. Marquis. However, some patients may not be able to get a measles booster vaccine because it is a live vaccine or because they cannot generate enough antibodies for it to be protective, she explained.
 

Three subgroups more likely to have deficits

The new study, which is one of the first to measure measles and mumps seroprevalence among patients with cancer in the modern era of cancer treatment, also identified three subgroups that more commonly had immunity deficits:  those aged 30-59 years; those with hematologic malignant neoplasms, and those who had received a hematopoietic cell transplant.

In the study, residual clinical plasma samples were obtained from 959 consecutive patients with cancer at Seattle Cancer Care Alliance and Fred Hutchinson in August 2019. These samples were tested for measles and mumps IgG by using a commercial enzyme-linked immunosorbent assay. In all, 60% of patients had a solid tumor and 40% had a blood cancer.

As noted above, the seroprevalence of measles antibodies was 0.75 and the seroprevalence of mumps antibodies was 0.62.

A study author explained why the study included mumps, a less threatening infection.

“We assessed mumps in this study out of interest to compare response in the MMR vaccine component – particularly as we could assess a potent vaccine (measles) versus one that has a weaker immunologic response (mumps). We remain worried about outbreaks of mumps as MMR vaccination rates drop across the U.S.,” wrote Steven Pergam, MD, MPH, infectious disease specialist at Fred Hutchinson, in an email.

Vaccination vigilance is one of the study’s messages. “We all need to do our part to make sure we are up to date with our vaccinations so we can make sure we protect those who are vulnerable,” said Ms. Krantz.

The study was funded by the National Cancer Institute and Seattle Cancer Care Alliance. Multiple study authors have ties to pharmaceutical companies.

A version of this article first appeared on Medscape.com.

Before the onslaught of COVID-19, researchers at the Fred Hutchinson Cancer Research Center in Seattle had another infectious disease worry: an “unprecedented” outbreak of measles.

“In 2019, we saw the most measles cases in any year since the 1990s,” said Sara Marquis, MPH, a clinical research coordinator at the center. The worry, she says, was that various oncology treatments, such as bone marrow transplantations and assorted biologics, “may leave cancer patients severely immunosuppressed” and thus vulnerable to infectious diseases.

Measles-related illness is typically not severe but can lead to pneumonia, deafness, and death, even in immunocompetent people, Ms. Marquis added.

So in 2019, a team at Fred Hutchinson initiated a study to get a sense of immunity to measles among patients with cancer.

They now report that of a group of 900-plus patients, 25% lacked protective antibodies for measles. That’s “significantly more” than the general population, in which about 8% of people lack these antibodies, Ms. Marquis said.

The study, published online in JAMA Network Open, also found that 38% lacked protection against the less-worrisome infectious disease of mumps, which is more than the 13% found in the general population.

“The scary thing about measles is that it is one of the most contagious diseases known,” Ms. Marquis told this news organization, adding that it is about twice as contagious as the COVID-19 Delta variant.

And it’s not just in the state of Washington. “We’re seeing it more and more in the community,” as various outbreaks continue to happen, she said.

“Deficits in protective antibodies underscore patients’ increased risk during outbreaks and emphasize the need for community-based efforts to increase herd immunity to protect this population,” the study authors conclude.

In short, administration of the measles-mumps-rubella (MMR) vaccine, introduced in 1963, must continue universally, they said

“We’ve had so many incredible advances in cancer treatment in recent years. … it would be devastating to see something like measles, which is a vaccine-preventable disease, come through and negate those efforts,” said study coauthor Elizabeth Krantz, MS, a biostatistician at Fred Hutchinson.

The health care teams and family caregivers of patients with cancer should also make sure they are vaccinated, said Ms. Marquis. However, some patients may not be able to get a measles booster vaccine because it is a live vaccine or because they cannot generate enough antibodies for it to be protective, she explained.
 

Three subgroups more likely to have deficits

The new study, which is one of the first to measure measles and mumps seroprevalence among patients with cancer in the modern era of cancer treatment, also identified three subgroups that more commonly had immunity deficits:  those aged 30-59 years; those with hematologic malignant neoplasms, and those who had received a hematopoietic cell transplant.

In the study, residual clinical plasma samples were obtained from 959 consecutive patients with cancer at Seattle Cancer Care Alliance and Fred Hutchinson in August 2019. These samples were tested for measles and mumps IgG by using a commercial enzyme-linked immunosorbent assay. In all, 60% of patients had a solid tumor and 40% had a blood cancer.

As noted above, the seroprevalence of measles antibodies was 0.75 and the seroprevalence of mumps antibodies was 0.62.

A study author explained why the study included mumps, a less threatening infection.

“We assessed mumps in this study out of interest to compare response in the MMR vaccine component – particularly as we could assess a potent vaccine (measles) versus one that has a weaker immunologic response (mumps). We remain worried about outbreaks of mumps as MMR vaccination rates drop across the U.S.,” wrote Steven Pergam, MD, MPH, infectious disease specialist at Fred Hutchinson, in an email.

Vaccination vigilance is one of the study’s messages. “We all need to do our part to make sure we are up to date with our vaccinations so we can make sure we protect those who are vulnerable,” said Ms. Krantz.

The study was funded by the National Cancer Institute and Seattle Cancer Care Alliance. Multiple study authors have ties to pharmaceutical companies.

A version of this article first appeared on Medscape.com.

Before the onslaught of COVID-19, researchers at the Fred Hutchinson Cancer Research Center in Seattle had another infectious disease worry: an “unprecedented” outbreak of measles.

“In 2019, we saw the most measles cases in any year since the 1990s,” said Sara Marquis, MPH, a clinical research coordinator at the center. The worry, she says, was that various oncology treatments, such as bone marrow transplantations and assorted biologics, “may leave cancer patients severely immunosuppressed” and thus vulnerable to infectious diseases.

Measles-related illness is typically not severe but can lead to pneumonia, deafness, and death, even in immunocompetent people, Ms. Marquis added.

So in 2019, a team at Fred Hutchinson initiated a study to get a sense of immunity to measles among patients with cancer.

They now report that of a group of 900-plus patients, 25% lacked protective antibodies for measles. That’s “significantly more” than the general population, in which about 8% of people lack these antibodies, Ms. Marquis said.

The study, published online in JAMA Network Open, also found that 38% lacked protection against the less-worrisome infectious disease of mumps, which is more than the 13% found in the general population.

“The scary thing about measles is that it is one of the most contagious diseases known,” Ms. Marquis told this news organization, adding that it is about twice as contagious as the COVID-19 Delta variant.

And it’s not just in the state of Washington. “We’re seeing it more and more in the community,” as various outbreaks continue to happen, she said.

“Deficits in protective antibodies underscore patients’ increased risk during outbreaks and emphasize the need for community-based efforts to increase herd immunity to protect this population,” the study authors conclude.

In short, administration of the measles-mumps-rubella (MMR) vaccine, introduced in 1963, must continue universally, they said

“We’ve had so many incredible advances in cancer treatment in recent years. … it would be devastating to see something like measles, which is a vaccine-preventable disease, come through and negate those efforts,” said study coauthor Elizabeth Krantz, MS, a biostatistician at Fred Hutchinson.

The health care teams and family caregivers of patients with cancer should also make sure they are vaccinated, said Ms. Marquis. However, some patients may not be able to get a measles booster vaccine because it is a live vaccine or because they cannot generate enough antibodies for it to be protective, she explained.
 

Three subgroups more likely to have deficits

The new study, which is one of the first to measure measles and mumps seroprevalence among patients with cancer in the modern era of cancer treatment, also identified three subgroups that more commonly had immunity deficits:  those aged 30-59 years; those with hematologic malignant neoplasms, and those who had received a hematopoietic cell transplant.

In the study, residual clinical plasma samples were obtained from 959 consecutive patients with cancer at Seattle Cancer Care Alliance and Fred Hutchinson in August 2019. These samples were tested for measles and mumps IgG by using a commercial enzyme-linked immunosorbent assay. In all, 60% of patients had a solid tumor and 40% had a blood cancer.

As noted above, the seroprevalence of measles antibodies was 0.75 and the seroprevalence of mumps antibodies was 0.62.

A study author explained why the study included mumps, a less threatening infection.

“We assessed mumps in this study out of interest to compare response in the MMR vaccine component – particularly as we could assess a potent vaccine (measles) versus one that has a weaker immunologic response (mumps). We remain worried about outbreaks of mumps as MMR vaccination rates drop across the U.S.,” wrote Steven Pergam, MD, MPH, infectious disease specialist at Fred Hutchinson, in an email.

Vaccination vigilance is one of the study’s messages. “We all need to do our part to make sure we are up to date with our vaccinations so we can make sure we protect those who are vulnerable,” said Ms. Krantz.

The study was funded by the National Cancer Institute and Seattle Cancer Care Alliance. Multiple study authors have ties to pharmaceutical companies.

A version of this article first appeared on Medscape.com.

The American Society for Clinical Pathology (ASCP), which represents over 100,000 pathologists and medical laboratory professionals, has called for a nationwide vaccination mandate. It is the first medical specialty society to do so, ASCP chief executive officer Blair Holladay, PhD, said in an interview.

However, the American Lung Association this week said it supports President Biden’s call for businesses to require their employees to be vaccinated. In addition, more than 50 medical societies, including ASCP, recently said they support vaccination mandates for health care workers.

In a position statement released Wednesday, ASCP recommended that every eligible American be vaccinated. “The U.S. Food and Drug Administration is soon expected to fully approve at least one COVID-19 vaccine, and when it does, we urge that vaccination requirements become the norm,” the society said.

Second, ASCP noted that at least 16 states have enacted some form of a ban on COVID-19 vaccine mandates or related requirements. These include blocking employment-based mandates, school vaccination or mask requirements, and vaccine passport requirements.

“These laws prolong the pandemic and threaten the health and safety of every American. They should be repealed or overturned immediately,” the association stated.

Third, ASCP said, it supports the guidance of the Centers for Disease Control and Prevention that masks should be worn indoors in public places in areas of substantial or high COVID-19 transmission.

“Before more people die, our elected leaders need to take serious and aggressive action to ensure that Americans get vaccinated, so we can end the pandemic, end patient and family suffering, end the fatalities, and get back to the lives we had before COVID-19,” the statement concluded.
 

Laboratories have to focus on COVID again

In his interview, Dr. Holladay noted that the eruption of the Delta variant across the country has again forced laboratories to focus on COVID-19 testing at the expense of necessary tests related to other diseases.

“Because 7 of 10 medical decisions depend on the laboratory, anything that interferes with that interferes with the needs of patient care, including preventive, chronic, and acute care services,” he said.

This is a major reason, he said, for ASCP to support a national vaccination mandate. “People have postponed treatment because of the inability to access medical care [for other conditions],” he noted. The same is true for preventive or diagnostic care such as biopsies for breast cancer and colonoscopies, he added.

“In many parts of the country, the throughput of COVID tests made it difficult for us to focus on tests for other acute conditions. It overwhelmed the laboratory personnel in terms of the number of tests being run.”
 

Returning to the ‘dark days’

This was a significant issue in the earlier part of the pandemic, Dr. Holladay recalled. The shortage of non-COVID lab capacity eased in the spring and early summer of 2021, when COVID-19 vaccines became widely available.

“But with the Delta variant, we’re going back to those dark days and creating the same bottleneck that we saw in the beginning,” he said.

Although the situation is worse in some states than others, Dr. Holladay added, some of the hardest-hit states like Florida and Texas have very large populations.

“This is not just about doctors, nurses, pathologists, and laboratory personnel being exhausted,” commented Kimberly Sanford, MD, president of ASCP, in a press release. “Laboratory medicine is absolutely necessary for accurate and timely diagnosis of disease, infection control, and effective treatment planning. It is an essential part of the health care system and often overwhelmed by the increasing number of coronavirus tests requiring immediate analysis.

“Such testing takes time and disproportionately consumes scarce equipment and other resources. It means those with cancer and other life-threatening conditions face serious delays in diagnosis and treatment. It delays medical diagnoses, erects barriers to preventative care, and prevents us from focusing on the significant health care needs of the population at large.”

A version of this article first appeared on Medscape.com.

The American Society for Clinical Pathology (ASCP), which represents over 100,000 pathologists and medical laboratory professionals, has called for a nationwide vaccination mandate. It is the first medical specialty society to do so, ASCP chief executive officer Blair Holladay, PhD, said in an interview.

However, the American Lung Association this week said it supports President Biden’s call for businesses to require their employees to be vaccinated. In addition, more than 50 medical societies, including ASCP, recently said they support vaccination mandates for health care workers.

In a position statement released Wednesday, ASCP recommended that every eligible American be vaccinated. “The U.S. Food and Drug Administration is soon expected to fully approve at least one COVID-19 vaccine, and when it does, we urge that vaccination requirements become the norm,” the society said.

Second, ASCP noted that at least 16 states have enacted some form of a ban on COVID-19 vaccine mandates or related requirements. These include blocking employment-based mandates, school vaccination or mask requirements, and vaccine passport requirements.

“These laws prolong the pandemic and threaten the health and safety of every American. They should be repealed or overturned immediately,” the association stated.

Third, ASCP said, it supports the guidance of the Centers for Disease Control and Prevention that masks should be worn indoors in public places in areas of substantial or high COVID-19 transmission.

“Before more people die, our elected leaders need to take serious and aggressive action to ensure that Americans get vaccinated, so we can end the pandemic, end patient and family suffering, end the fatalities, and get back to the lives we had before COVID-19,” the statement concluded.
 

Laboratories have to focus on COVID again

In his interview, Dr. Holladay noted that the eruption of the Delta variant across the country has again forced laboratories to focus on COVID-19 testing at the expense of necessary tests related to other diseases.

“Because 7 of 10 medical decisions depend on the laboratory, anything that interferes with that interferes with the needs of patient care, including preventive, chronic, and acute care services,” he said.

This is a major reason, he said, for ASCP to support a national vaccination mandate. “People have postponed treatment because of the inability to access medical care [for other conditions],” he noted. The same is true for preventive or diagnostic care such as biopsies for breast cancer and colonoscopies, he added.

“In many parts of the country, the throughput of COVID tests made it difficult for us to focus on tests for other acute conditions. It overwhelmed the laboratory personnel in terms of the number of tests being run.”
 

Returning to the ‘dark days’

This was a significant issue in the earlier part of the pandemic, Dr. Holladay recalled. The shortage of non-COVID lab capacity eased in the spring and early summer of 2021, when COVID-19 vaccines became widely available.

“But with the Delta variant, we’re going back to those dark days and creating the same bottleneck that we saw in the beginning,” he said.

Although the situation is worse in some states than others, Dr. Holladay added, some of the hardest-hit states like Florida and Texas have very large populations.

“This is not just about doctors, nurses, pathologists, and laboratory personnel being exhausted,” commented Kimberly Sanford, MD, president of ASCP, in a press release. “Laboratory medicine is absolutely necessary for accurate and timely diagnosis of disease, infection control, and effective treatment planning. It is an essential part of the health care system and often overwhelmed by the increasing number of coronavirus tests requiring immediate analysis.

“Such testing takes time and disproportionately consumes scarce equipment and other resources. It means those with cancer and other life-threatening conditions face serious delays in diagnosis and treatment. It delays medical diagnoses, erects barriers to preventative care, and prevents us from focusing on the significant health care needs of the population at large.”

A version of this article first appeared on Medscape.com.

The American Society for Clinical Pathology (ASCP), which represents over 100,000 pathologists and medical laboratory professionals, has called for a nationwide vaccination mandate. It is the first medical specialty society to do so, ASCP chief executive officer Blair Holladay, PhD, said in an interview.

However, the American Lung Association this week said it supports President Biden’s call for businesses to require their employees to be vaccinated. In addition, more than 50 medical societies, including ASCP, recently said they support vaccination mandates for health care workers.

In a position statement released Wednesday, ASCP recommended that every eligible American be vaccinated. “The U.S. Food and Drug Administration is soon expected to fully approve at least one COVID-19 vaccine, and when it does, we urge that vaccination requirements become the norm,” the society said.

Second, ASCP noted that at least 16 states have enacted some form of a ban on COVID-19 vaccine mandates or related requirements. These include blocking employment-based mandates, school vaccination or mask requirements, and vaccine passport requirements.

“These laws prolong the pandemic and threaten the health and safety of every American. They should be repealed or overturned immediately,” the association stated.

Third, ASCP said, it supports the guidance of the Centers for Disease Control and Prevention that masks should be worn indoors in public places in areas of substantial or high COVID-19 transmission.

“Before more people die, our elected leaders need to take serious and aggressive action to ensure that Americans get vaccinated, so we can end the pandemic, end patient and family suffering, end the fatalities, and get back to the lives we had before COVID-19,” the statement concluded.
 

Laboratories have to focus on COVID again

In his interview, Dr. Holladay noted that the eruption of the Delta variant across the country has again forced laboratories to focus on COVID-19 testing at the expense of necessary tests related to other diseases.

“Because 7 of 10 medical decisions depend on the laboratory, anything that interferes with that interferes with the needs of patient care, including preventive, chronic, and acute care services,” he said.

This is a major reason, he said, for ASCP to support a national vaccination mandate. “People have postponed treatment because of the inability to access medical care [for other conditions],” he noted. The same is true for preventive or diagnostic care such as biopsies for breast cancer and colonoscopies, he added.

“In many parts of the country, the throughput of COVID tests made it difficult for us to focus on tests for other acute conditions. It overwhelmed the laboratory personnel in terms of the number of tests being run.”
 

Returning to the ‘dark days’

This was a significant issue in the earlier part of the pandemic, Dr. Holladay recalled. The shortage of non-COVID lab capacity eased in the spring and early summer of 2021, when COVID-19 vaccines became widely available.

“But with the Delta variant, we’re going back to those dark days and creating the same bottleneck that we saw in the beginning,” he said.

Although the situation is worse in some states than others, Dr. Holladay added, some of the hardest-hit states like Florida and Texas have very large populations.

“This is not just about doctors, nurses, pathologists, and laboratory personnel being exhausted,” commented Kimberly Sanford, MD, president of ASCP, in a press release. “Laboratory medicine is absolutely necessary for accurate and timely diagnosis of disease, infection control, and effective treatment planning. It is an essential part of the health care system and often overwhelmed by the increasing number of coronavirus tests requiring immediate analysis.

“Such testing takes time and disproportionately consumes scarce equipment and other resources. It means those with cancer and other life-threatening conditions face serious delays in diagnosis and treatment. It delays medical diagnoses, erects barriers to preventative care, and prevents us from focusing on the significant health care needs of the population at large.”

A version of this article first appeared on Medscape.com.

A remote monitoring system was highly effective in managing symptoms and improving quality of life among patients with cancer who were receiving chemotherapy, say researchers reporting the first clinical trial of the new approach.

The study tested the Advanced Symptom Management System (ASyMS) for patients with various cancer types who were undergoing treatment at cancer centers in several European countries. The study primarily focused on patients who were being treated with curative intent.

The 24-hour monitoring system optimized symptom management in a manner safe, secure, and in “real time,” the team reports. This is particularly relevant during the COVID-19 pandemic, they note.

“Our findings suggest that an evidence based remote monitoring intervention, such as ASyMS, has potential for implementation into routine care to make a meaningful difference to people with cancer,” the authors conclude.

The findings were published online in BMJ.

The results show that “ASyMS can be implemented across multiple countries within diverse health care systems,” commented lead author Roma Maguire, PhD, a professor of digital health and care at the University of Strathclyde, in Glasgow, and director of the Health and Care Futures initiative.

So far, the system has only been used in clinical research studies, but “our findings do suggest that it is feasible to implement our system on a wider scale,” she added.

The study cohort included 829 patients with various cancers, including nonmetastatic breast cancer, colorectal cancer, Hodgkin disease, and non-Hodgkin lymphoma. The patients were receiving first-line adjuvant chemotherapy or chemotherapy for the first time in 5 years. They were recruited from 12 cancer centers in Austria, Greece, Norway, the Republic of Ireland, and the United Kingdom.

Patients were randomly assigned to receive ASyMS (n = 415) or standard care (n = 414) during six cycles of chemotherapy.

The primary outcome was symptom burden, as determined using the Memorial Symptom Assessment Scale. Secondary outcomes included health-related quality of life, as determined by results on the Functional Assessment of Cancer Therapy–General, the Supportive Care Needs Survey–Short Form, the State-Trait Anxiety Inventory–Revised, the Communication and Attitudinal Self-Efficacy scale for cancer, and the Work Limitations Questionnaire.

Patients in the intervention group completed a daily symptom questionnaire on a handheld ASyMS device, which generated alerts to health care professionals if any intervention was needed. The patients were also provided with advice and information on how to manage their symptoms themselves.

Among patients using ASyMS, symptom burden remained at prechemotherapy levels over all six chemotherapy cycles. Conversely, the control group reported an increase in symptom burden from cycle 1; symptom burden slowly decreased during the remaining chemotherapy cycles.

Overall, the investigators found that, among the patients who used ASyMS, psychological and physical symptoms were significantly reduced, along with the level of distress associated with each symptom.

In addition, for the patients who used ASyMS, health-related quality-of-life scores were higher across all cycles. The authors note that the improvements in health-related quality of life are consistent with findings from recent trials of the use of remote monitoring systems in chemotherapy care. The intervention group also experienced significant improvements regarding the need for supportive care.

Improvements in symptom burden differed among countries. The greatest improvements were seen among patients with breast cancer, Hodgkin disease, or non-Hodgkin lymphoma in Austria, Ireland, and the United Kingdom. The reasons for these differences are unclear, the authors note. ASyMS was developed in the United Kingdom, and it’s possible that ASyMS is more effective in countries that have health care systems similar to the system in the United Kingdom, they suggest.

The incidence of adverse events was similar for the two groups, although the rate of neutropenia was higher among patients using ASyMS (n = 125; 64%) in comparison with the standard-care group ( n = 71; 36%). Three deaths occurred in each study arm. The number of planned hospital admissions was similar between the two groups (34 vs. 38), as was the number of unplanned hospital admissions (120 vs. 109). No ASyMS device-related incidents were reported.

The trial was funded by the European Commission and was sponsored by the University of Strathclyde. Dr. Maguire has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A remote monitoring system was highly effective in managing symptoms and improving quality of life among patients with cancer who were receiving chemotherapy, say researchers reporting the first clinical trial of the new approach.

The study tested the Advanced Symptom Management System (ASyMS) for patients with various cancer types who were undergoing treatment at cancer centers in several European countries. The study primarily focused on patients who were being treated with curative intent.

The 24-hour monitoring system optimized symptom management in a manner safe, secure, and in “real time,” the team reports. This is particularly relevant during the COVID-19 pandemic, they note.

“Our findings suggest that an evidence based remote monitoring intervention, such as ASyMS, has potential for implementation into routine care to make a meaningful difference to people with cancer,” the authors conclude.

The findings were published online in BMJ.

The results show that “ASyMS can be implemented across multiple countries within diverse health care systems,” commented lead author Roma Maguire, PhD, a professor of digital health and care at the University of Strathclyde, in Glasgow, and director of the Health and Care Futures initiative.

So far, the system has only been used in clinical research studies, but “our findings do suggest that it is feasible to implement our system on a wider scale,” she added.

The study cohort included 829 patients with various cancers, including nonmetastatic breast cancer, colorectal cancer, Hodgkin disease, and non-Hodgkin lymphoma. The patients were receiving first-line adjuvant chemotherapy or chemotherapy for the first time in 5 years. They were recruited from 12 cancer centers in Austria, Greece, Norway, the Republic of Ireland, and the United Kingdom.

Patients were randomly assigned to receive ASyMS (n = 415) or standard care (n = 414) during six cycles of chemotherapy.

The primary outcome was symptom burden, as determined using the Memorial Symptom Assessment Scale. Secondary outcomes included health-related quality of life, as determined by results on the Functional Assessment of Cancer Therapy–General, the Supportive Care Needs Survey–Short Form, the State-Trait Anxiety Inventory–Revised, the Communication and Attitudinal Self-Efficacy scale for cancer, and the Work Limitations Questionnaire.

Patients in the intervention group completed a daily symptom questionnaire on a handheld ASyMS device, which generated alerts to health care professionals if any intervention was needed. The patients were also provided with advice and information on how to manage their symptoms themselves.

Among patients using ASyMS, symptom burden remained at prechemotherapy levels over all six chemotherapy cycles. Conversely, the control group reported an increase in symptom burden from cycle 1; symptom burden slowly decreased during the remaining chemotherapy cycles.

Overall, the investigators found that, among the patients who used ASyMS, psychological and physical symptoms were significantly reduced, along with the level of distress associated with each symptom.

In addition, for the patients who used ASyMS, health-related quality-of-life scores were higher across all cycles. The authors note that the improvements in health-related quality of life are consistent with findings from recent trials of the use of remote monitoring systems in chemotherapy care. The intervention group also experienced significant improvements regarding the need for supportive care.

Improvements in symptom burden differed among countries. The greatest improvements were seen among patients with breast cancer, Hodgkin disease, or non-Hodgkin lymphoma in Austria, Ireland, and the United Kingdom. The reasons for these differences are unclear, the authors note. ASyMS was developed in the United Kingdom, and it’s possible that ASyMS is more effective in countries that have health care systems similar to the system in the United Kingdom, they suggest.

The incidence of adverse events was similar for the two groups, although the rate of neutropenia was higher among patients using ASyMS (n = 125; 64%) in comparison with the standard-care group ( n = 71; 36%). Three deaths occurred in each study arm. The number of planned hospital admissions was similar between the two groups (34 vs. 38), as was the number of unplanned hospital admissions (120 vs. 109). No ASyMS device-related incidents were reported.

The trial was funded by the European Commission and was sponsored by the University of Strathclyde. Dr. Maguire has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A remote monitoring system was highly effective in managing symptoms and improving quality of life among patients with cancer who were receiving chemotherapy, say researchers reporting the first clinical trial of the new approach.

The study tested the Advanced Symptom Management System (ASyMS) for patients with various cancer types who were undergoing treatment at cancer centers in several European countries. The study primarily focused on patients who were being treated with curative intent.

The 24-hour monitoring system optimized symptom management in a manner safe, secure, and in “real time,” the team reports. This is particularly relevant during the COVID-19 pandemic, they note.

“Our findings suggest that an evidence based remote monitoring intervention, such as ASyMS, has potential for implementation into routine care to make a meaningful difference to people with cancer,” the authors conclude.

The findings were published online in BMJ.

The results show that “ASyMS can be implemented across multiple countries within diverse health care systems,” commented lead author Roma Maguire, PhD, a professor of digital health and care at the University of Strathclyde, in Glasgow, and director of the Health and Care Futures initiative.

So far, the system has only been used in clinical research studies, but “our findings do suggest that it is feasible to implement our system on a wider scale,” she added.

The study cohort included 829 patients with various cancers, including nonmetastatic breast cancer, colorectal cancer, Hodgkin disease, and non-Hodgkin lymphoma. The patients were receiving first-line adjuvant chemotherapy or chemotherapy for the first time in 5 years. They were recruited from 12 cancer centers in Austria, Greece, Norway, the Republic of Ireland, and the United Kingdom.

Patients were randomly assigned to receive ASyMS (n = 415) or standard care (n = 414) during six cycles of chemotherapy.

The primary outcome was symptom burden, as determined using the Memorial Symptom Assessment Scale. Secondary outcomes included health-related quality of life, as determined by results on the Functional Assessment of Cancer Therapy–General, the Supportive Care Needs Survey–Short Form, the State-Trait Anxiety Inventory–Revised, the Communication and Attitudinal Self-Efficacy scale for cancer, and the Work Limitations Questionnaire.

Patients in the intervention group completed a daily symptom questionnaire on a handheld ASyMS device, which generated alerts to health care professionals if any intervention was needed. The patients were also provided with advice and information on how to manage their symptoms themselves.

Among patients using ASyMS, symptom burden remained at prechemotherapy levels over all six chemotherapy cycles. Conversely, the control group reported an increase in symptom burden from cycle 1; symptom burden slowly decreased during the remaining chemotherapy cycles.

Overall, the investigators found that, among the patients who used ASyMS, psychological and physical symptoms were significantly reduced, along with the level of distress associated with each symptom.

In addition, for the patients who used ASyMS, health-related quality-of-life scores were higher across all cycles. The authors note that the improvements in health-related quality of life are consistent with findings from recent trials of the use of remote monitoring systems in chemotherapy care. The intervention group also experienced significant improvements regarding the need for supportive care.

Improvements in symptom burden differed among countries. The greatest improvements were seen among patients with breast cancer, Hodgkin disease, or non-Hodgkin lymphoma in Austria, Ireland, and the United Kingdom. The reasons for these differences are unclear, the authors note. ASyMS was developed in the United Kingdom, and it’s possible that ASyMS is more effective in countries that have health care systems similar to the system in the United Kingdom, they suggest.

The incidence of adverse events was similar for the two groups, although the rate of neutropenia was higher among patients using ASyMS (n = 125; 64%) in comparison with the standard-care group ( n = 71; 36%). Three deaths occurred in each study arm. The number of planned hospital admissions was similar between the two groups (34 vs. 38), as was the number of unplanned hospital admissions (120 vs. 109). No ASyMS device-related incidents were reported.

The trial was funded by the European Commission and was sponsored by the University of Strathclyde. Dr. Maguire has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Many of the changes to cancer clinical trials forced through by the COVID-19 pandemic should remain, as they have made trials “more patient centered and efficient,” according to a group of thought leaders in oncology.

Among the potential improvements were more efficient study enrollment through secure electronic platforms, direct shipment of oral drugs to patients, remote assessment of adverse events, and streamlined data collection.

These changes should be implemented on a permanent basis, the group argues in a commentary published online July 21, 2021, in Cancer Discovery, a journal of the American Association for Cancer Research.

“The ability to distribute oral investigational drugs by mail to patients at their home has probably been the single most impactful change to clinical trial conduct, linked with virtual visits with patients to assess side effects and symptoms,” commented lead author Keith Flaherty, MD, who is director of clinical research at Massachusetts General Hospital, a professor at Harvard Medical School, Boston, and a member of the AACR board of directors.

“This has made it more feasible for patients for whom participation in clinical trials poses a disruption of their ability to work or provide care for family members to participate in trials,” he added in a press statement issued by the AACR.
 

Pandemic halted many clinical trials

A survey of cancer programs in early 2020 showed that nearly 60% halted screening and/or enrollment for at least some trials because of COVID-19.

“In the spring of 2020, clinical trial conduct halted and then restarted focusing on the bare minimum procedures that first allowed patients continued access to their experimental therapies, and then allowed clinical trial sites and sponsors to collect information on the effects of the therapies,” the authors said.

“The COVID-19–induced changes to clinical trials were a big challenge, probably the largest change in clinical trial conduct since the start of modern oncology clinical testing,” they commented.

“But it also represents an opportunity to rethink the key aspects of clinical trial conduct that are strictly necessary to reach the goal of testing the effectiveness of cancer therapies, and which others are dispensable or provide only minor additional contributions,” they added.

As previously reported at the time by this news organization, efforts to find alternative approaches to conducting trials amid the pandemic led to the emergence of a few “silver linings.”

Key adaptations made to clinical trials and highlighted by the authors include:

• Uptake of remote consenting and telemedicine
• Use of alternative laboratories and imaging centers
• Delivery or administration of investigational drugs at patients’ homes or local clinics
• Commercial attainment of study drugs already approved for other indications

Indeed, the restrictions encountered during the pandemic underscore the importance of designing patient-centered trials versus study site–centered trials, added Antoni Ribas, MD, commentary coauthor and immediate past president of the AACR.

Many of the changes implemented during the pandemic could help increase access for patients living in underserved communities who are underrepresented in clinical trials, he explained.
 

Harnessing the lessons learned

The authors also recommended the following additional adaptations, which they believe will enhance efficiency and further expand access to clinical trials:

• Incorporating patient-reported outcomes and alternative endpoints in efficacy assessments
• Aiming for 100% remote drug infusions and monitoring
• Increasing funding for clinical trials conducted in underserved communities
• Expanding clinical trial eligibility to include patients with a wide range of comorbidities
• Reducing collection of low-grade adverse events and allowing minor protocol deviations

The group’s recommendations are based on discussions by the AACR COVID-19 and Cancer Task Force, in which they participated.

The American Society of Clinical Oncology is also working to leverage pandemic-related lessons to streamline care and trial planning.

ASCO’s “Road to Recovery” recommendations, published in December 2020, aim to “ensure lessons learned from the COVID-19 experience are used to craft a more equitable, accessible, and efficient clinical research system that protects patient safety, ensures scientific integrity, and maintains data quality,” the authors explained.

Dr. Flaherty and colleagues further underscore the importance of focusing on improvements going forward.

“Guided by lessons learned, many of the remote assessments and trial efficiencies deployed during the pandemic can be preserved and improved upon. We strongly encourage use of these streamlined procedures where appropriate in future prospectively designed cancer clinical trials,” they wrote.

Dr. Flaherty reported receiving personal fees from numerous pharmaceutical companies. Dr. Ribas reported receiving grants from Agilent and Bristol Myers Squibb.

A version of this article first appeared on Medscape.com.

Many of the changes to cancer clinical trials forced through by the COVID-19 pandemic should remain, as they have made trials “more patient centered and efficient,” according to a group of thought leaders in oncology.

Among the potential improvements were more efficient study enrollment through secure electronic platforms, direct shipment of oral drugs to patients, remote assessment of adverse events, and streamlined data collection.

These changes should be implemented on a permanent basis, the group argues in a commentary published online July 21, 2021, in Cancer Discovery, a journal of the American Association for Cancer Research.

“The ability to distribute oral investigational drugs by mail to patients at their home has probably been the single most impactful change to clinical trial conduct, linked with virtual visits with patients to assess side effects and symptoms,” commented lead author Keith Flaherty, MD, who is director of clinical research at Massachusetts General Hospital, a professor at Harvard Medical School, Boston, and a member of the AACR board of directors.

“This has made it more feasible for patients for whom participation in clinical trials poses a disruption of their ability to work or provide care for family members to participate in trials,” he added in a press statement issued by the AACR.
 

Pandemic halted many clinical trials

A survey of cancer programs in early 2020 showed that nearly 60% halted screening and/or enrollment for at least some trials because of COVID-19.

“In the spring of 2020, clinical trial conduct halted and then restarted focusing on the bare minimum procedures that first allowed patients continued access to their experimental therapies, and then allowed clinical trial sites and sponsors to collect information on the effects of the therapies,” the authors said.

“The COVID-19–induced changes to clinical trials were a big challenge, probably the largest change in clinical trial conduct since the start of modern oncology clinical testing,” they commented.

“But it also represents an opportunity to rethink the key aspects of clinical trial conduct that are strictly necessary to reach the goal of testing the effectiveness of cancer therapies, and which others are dispensable or provide only minor additional contributions,” they added.

As previously reported at the time by this news organization, efforts to find alternative approaches to conducting trials amid the pandemic led to the emergence of a few “silver linings.”

Key adaptations made to clinical trials and highlighted by the authors include:

• Uptake of remote consenting and telemedicine
• Use of alternative laboratories and imaging centers
• Delivery or administration of investigational drugs at patients’ homes or local clinics
• Commercial attainment of study drugs already approved for other indications

Indeed, the restrictions encountered during the pandemic underscore the importance of designing patient-centered trials versus study site–centered trials, added Antoni Ribas, MD, commentary coauthor and immediate past president of the AACR.

Many of the changes implemented during the pandemic could help increase access for patients living in underserved communities who are underrepresented in clinical trials, he explained.
 

Harnessing the lessons learned

The authors also recommended the following additional adaptations, which they believe will enhance efficiency and further expand access to clinical trials:

• Incorporating patient-reported outcomes and alternative endpoints in efficacy assessments
• Aiming for 100% remote drug infusions and monitoring
• Increasing funding for clinical trials conducted in underserved communities
• Expanding clinical trial eligibility to include patients with a wide range of comorbidities
• Reducing collection of low-grade adverse events and allowing minor protocol deviations

The group’s recommendations are based on discussions by the AACR COVID-19 and Cancer Task Force, in which they participated.

The American Society of Clinical Oncology is also working to leverage pandemic-related lessons to streamline care and trial planning.

ASCO’s “Road to Recovery” recommendations, published in December 2020, aim to “ensure lessons learned from the COVID-19 experience are used to craft a more equitable, accessible, and efficient clinical research system that protects patient safety, ensures scientific integrity, and maintains data quality,” the authors explained.

Dr. Flaherty and colleagues further underscore the importance of focusing on improvements going forward.

“Guided by lessons learned, many of the remote assessments and trial efficiencies deployed during the pandemic can be preserved and improved upon. We strongly encourage use of these streamlined procedures where appropriate in future prospectively designed cancer clinical trials,” they wrote.

Dr. Flaherty reported receiving personal fees from numerous pharmaceutical companies. Dr. Ribas reported receiving grants from Agilent and Bristol Myers Squibb.

A version of this article first appeared on Medscape.com.

Many of the changes to cancer clinical trials forced through by the COVID-19 pandemic should remain, as they have made trials “more patient centered and efficient,” according to a group of thought leaders in oncology.

Among the potential improvements were more efficient study enrollment through secure electronic platforms, direct shipment of oral drugs to patients, remote assessment of adverse events, and streamlined data collection.

These changes should be implemented on a permanent basis, the group argues in a commentary published online July 21, 2021, in Cancer Discovery, a journal of the American Association for Cancer Research.

“The ability to distribute oral investigational drugs by mail to patients at their home has probably been the single most impactful change to clinical trial conduct, linked with virtual visits with patients to assess side effects and symptoms,” commented lead author Keith Flaherty, MD, who is director of clinical research at Massachusetts General Hospital, a professor at Harvard Medical School, Boston, and a member of the AACR board of directors.

“This has made it more feasible for patients for whom participation in clinical trials poses a disruption of their ability to work or provide care for family members to participate in trials,” he added in a press statement issued by the AACR.
 

Pandemic halted many clinical trials

A survey of cancer programs in early 2020 showed that nearly 60% halted screening and/or enrollment for at least some trials because of COVID-19.

“In the spring of 2020, clinical trial conduct halted and then restarted focusing on the bare minimum procedures that first allowed patients continued access to their experimental therapies, and then allowed clinical trial sites and sponsors to collect information on the effects of the therapies,” the authors said.

“The COVID-19–induced changes to clinical trials were a big challenge, probably the largest change in clinical trial conduct since the start of modern oncology clinical testing,” they commented.

“But it also represents an opportunity to rethink the key aspects of clinical trial conduct that are strictly necessary to reach the goal of testing the effectiveness of cancer therapies, and which others are dispensable or provide only minor additional contributions,” they added.

As previously reported at the time by this news organization, efforts to find alternative approaches to conducting trials amid the pandemic led to the emergence of a few “silver linings.”

Key adaptations made to clinical trials and highlighted by the authors include:

• Uptake of remote consenting and telemedicine
• Use of alternative laboratories and imaging centers
• Delivery or administration of investigational drugs at patients’ homes or local clinics
• Commercial attainment of study drugs already approved for other indications

Indeed, the restrictions encountered during the pandemic underscore the importance of designing patient-centered trials versus study site–centered trials, added Antoni Ribas, MD, commentary coauthor and immediate past president of the AACR.

Many of the changes implemented during the pandemic could help increase access for patients living in underserved communities who are underrepresented in clinical trials, he explained.
 

Harnessing the lessons learned

The authors also recommended the following additional adaptations, which they believe will enhance efficiency and further expand access to clinical trials:

• Incorporating patient-reported outcomes and alternative endpoints in efficacy assessments
• Aiming for 100% remote drug infusions and monitoring
• Increasing funding for clinical trials conducted in underserved communities
• Expanding clinical trial eligibility to include patients with a wide range of comorbidities
• Reducing collection of low-grade adverse events and allowing minor protocol deviations

The group’s recommendations are based on discussions by the AACR COVID-19 and Cancer Task Force, in which they participated.

The American Society of Clinical Oncology is also working to leverage pandemic-related lessons to streamline care and trial planning.

ASCO’s “Road to Recovery” recommendations, published in December 2020, aim to “ensure lessons learned from the COVID-19 experience are used to craft a more equitable, accessible, and efficient clinical research system that protects patient safety, ensures scientific integrity, and maintains data quality,” the authors explained.

Dr. Flaherty and colleagues further underscore the importance of focusing on improvements going forward.

“Guided by lessons learned, many of the remote assessments and trial efficiencies deployed during the pandemic can be preserved and improved upon. We strongly encourage use of these streamlined procedures where appropriate in future prospectively designed cancer clinical trials,” they wrote.

Dr. Flaherty reported receiving personal fees from numerous pharmaceutical companies. Dr. Ribas reported receiving grants from Agilent and Bristol Myers Squibb.

A version of this article first appeared on Medscape.com.

Terminally ill patients with advanced cancer may not be receiving adequate pain management, according to new findings.

There has been a sharp decrease in access to opioids during the past decade, and many patients are going to emergency departments for pain treatment.

Overall, during the study period (2007-2017), there was a 34% reduction in the number of opioid prescriptions filled per patient and a 38% reduction in the total dose of opioids filled near the end of life.

There was a dramatic drop in the use of long-acting opioids, which can provide patients with more consistent pain relief and are important for managing severe cancer pain. The investigators’ results show that during the study period, the number of long-acting opioid prescriptions filled per patient fell by 50%.

“We do believe that the decline in cancer patients’ access to opioids near the end of life is likely attributable to the efforts to curtail opioid misuse,” commented lead author Andrea Enzinger, MD, a medical oncologist at Dana-Farber Cancer Institute, Boston.

The study was published online July 22 in the Journal of Clinical Oncology.

“The study provides fascinating data that support our clinical observations,” said Marcin Chwistek, MD, FAAHPM, director of the supportive oncology and palliative care program at Fox Chase Cancer Center, Philadelphia, who was asked for comment. “Primarily, we have noticed a heightened reluctance on the parts of patients with cancer, including those with advanced cancer, to take opioids in general.”
 

Many factors involved

The crisis of opioid misuse and abuse led to the implementation of regulations to curb inappropriate prescribing. But these restrictions on opioid prescribing may have unintended consequences for patients with advanced, incurable malignancies who are experiencing pain.

“Many but not all opioid regulations specifically exclude cancer patients,” said Dr. Enzinger. “However, the cumulative effect of these regulations may have had a chilling effect on providers’ comfort or willingness to prescribe opioids, even for cancer pain.”

She said in an interview that the prescribing of opioids has become much more difficult. Prescribers are often required to sign an opioid agreement with patients prior to providing them with opioids. Health care professionals may need to use a two-factor authentication to prescribe, and prescribers in 49 of 50 U.S. states are required to check electronic prescription drug monitoring programs prior to providing the prescription.

“After the medications are prescribed, insurance companies require prior-authorization paperwork before filling the medications, particularly for long-acting opioids or high-dose opioids,” Dr. Enzinger said. “These barriers pile up and make the whole process onerous and time consuming.”

Patient factors may also have contributed to the decline in use.

“Cancer patients are often very hesitant to use opioids to treat their pain, as they worry about becoming addicted or being labeled a ‘pill seeker,’” she explained. “Also, the added regulations, such as requirements for prior authorization paperwork, signing opioid agreements, and so on, may add to the stigma of opioid therapy and send a message to patients that these medications are inherently dangerous.”

Dr. Enzinger added that there are legitimate reasons why patients may not want to use opioids and that these should be respected. “But addiction risk should really not weigh into the decisions about pain management for patients who are dying from cancer,” she said.
 

Decline in opioid dose and prescriptions

Dr. Enzinger and colleagues used administrative data from the Centers for Medicare & Medicaid Services to identify 270,632 Medicare fee-for-service patients who had cancers that were associated with poor prognoses and who died from 2007 to 2017. During this period, the opioid crisis was first recognized. There followed legislative reforms and subsequent declines in population-based opioid prescribing.

Among the patients in the study, the most common cancers were lung, colorectal, pancreatic, prostate, and breast cancers; 166,962 patients (61.7%) were enrolled in hospice before death. This percentage increased from 57.1% in 2007 to 66.2% in 2017 (P for trend < .001).

From 2007 to 2017, the proportion of patients filling greater than or equal to 1 opioid prescriptions declined from 42.0% to 35.5%. The proportion declined faster from 2012-2017 than from 2007-2011.

The proportion of patients who filled prescriptions for long-acting opioids dropped from 18.1% to 11.5%. Here again, the decline was faster from 2012-2017 than from 2007-2011. Prescriptions for strong short-acting opioids declined from 31.7% to 28.5%. Prescribing was initially stable from 2007-2011 and began to decline in 2012. Conversely, prescriptions for weak short-acting opioids dropped from 8.4% to 6.5% from 2007-2011 and then stabilized after 2012.

The mean daily dose fell 24.5%, from 85.6 morphine milligram equivalents per day (MMED) to 64.6 MMED. Overall, the total amount of opioids prescribed per decedent fell 38.0%, from 1,075 MMEs per person to 666 MMEs.

At the same time, the proportion of patients who visited EDs increased 50.8%, from 13.2% to 19.9%.
 

Experts weigh in

Approached for an independent comment, Amit Barochia, MD, a hematologist/oncologist with Health First Medical Group, Titusville, Fla., commented that the decline could be due, in part, to greater vigilance and awareness by physicians in light of more stringent requirements and of federal and state regulations. “Some physicians are avoiding prescribing opioids due to more regulations and requirements as well, which is routing patients to the ER for pain relief,” he said.

Dr. Barochia agreed that some of the decline could be due to patient factors. “I do think that some of the patients are hesitant about considering opioid use for better pain relief, in part due to fear of addiction as well as complications arising from their use,” he said. “This is likely resulting from more awareness in the community about their adverse effects.

“That awareness could come from aggressive media coverage as well as social media,” he continued. “It is also true that there is a difficulty in getting authorization for certain opioid products, which is delaying the onset of a proper pain regimen that would help to provide adequate pain relief early on.”

For patients with advanced cancer, earlier referral to palliative care would be beneficial, Dr. Barochia pointed out, because this would allow for a more in-depth discussion about pain in addition to addressing the physical and mental symptoms associated with cancer.

Fox Chase Cancer Center’s Dr. Chwistek noted that patients and their caregivers are often apprehensive about the potential adverse effects of opioids, because they often hear about community-based opioid overdoses and are fearful of taking the medications. “Additionally, it has become increasingly challenging to fill opioid prescriptions at local pharmacies, due to quantity limitations, ubiquitous need for prior authorizations, and stigma,” he said.

The fear of addiction is often brought up by the patients during clinic visits, and insurers and pharmacies have imposed many limits on opioid prescribing. “Most of these can be overcome with prior authorizations, but not always, and prior authorizations are time consuming, confusing, and very frustrating for patients,” he said in an interview.

These findings suggest that not enough patients are getting optimal palliative care. “One of the primary tenets of palliative care is optimal symptom control, including pain,” said Dr. Chwistek. “Palliative care teams have the experience and insight needed to help patients overcome the barriers to appropriate pain control. Education, support, and advocacy are critical to ensure that patients’ pain is appropriately addressed.”

The study was funded by a grant from the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services.

A version of this article first appeared on Medscape.com.

Terminally ill patients with advanced cancer may not be receiving adequate pain management, according to new findings.

There has been a sharp decrease in access to opioids during the past decade, and many patients are going to emergency departments for pain treatment.

Overall, during the study period (2007-2017), there was a 34% reduction in the number of opioid prescriptions filled per patient and a 38% reduction in the total dose of opioids filled near the end of life.

There was a dramatic drop in the use of long-acting opioids, which can provide patients with more consistent pain relief and are important for managing severe cancer pain. The investigators’ results show that during the study period, the number of long-acting opioid prescriptions filled per patient fell by 50%.

“We do believe that the decline in cancer patients’ access to opioids near the end of life is likely attributable to the efforts to curtail opioid misuse,” commented lead author Andrea Enzinger, MD, a medical oncologist at Dana-Farber Cancer Institute, Boston.

The study was published online July 22 in the Journal of Clinical Oncology.

“The study provides fascinating data that support our clinical observations,” said Marcin Chwistek, MD, FAAHPM, director of the supportive oncology and palliative care program at Fox Chase Cancer Center, Philadelphia, who was asked for comment. “Primarily, we have noticed a heightened reluctance on the parts of patients with cancer, including those with advanced cancer, to take opioids in general.”
 

Many factors involved

The crisis of opioid misuse and abuse led to the implementation of regulations to curb inappropriate prescribing. But these restrictions on opioid prescribing may have unintended consequences for patients with advanced, incurable malignancies who are experiencing pain.

“Many but not all opioid regulations specifically exclude cancer patients,” said Dr. Enzinger. “However, the cumulative effect of these regulations may have had a chilling effect on providers’ comfort or willingness to prescribe opioids, even for cancer pain.”

She said in an interview that the prescribing of opioids has become much more difficult. Prescribers are often required to sign an opioid agreement with patients prior to providing them with opioids. Health care professionals may need to use a two-factor authentication to prescribe, and prescribers in 49 of 50 U.S. states are required to check electronic prescription drug monitoring programs prior to providing the prescription.

“After the medications are prescribed, insurance companies require prior-authorization paperwork before filling the medications, particularly for long-acting opioids or high-dose opioids,” Dr. Enzinger said. “These barriers pile up and make the whole process onerous and time consuming.”

Patient factors may also have contributed to the decline in use.

“Cancer patients are often very hesitant to use opioids to treat their pain, as they worry about becoming addicted or being labeled a ‘pill seeker,’” she explained. “Also, the added regulations, such as requirements for prior authorization paperwork, signing opioid agreements, and so on, may add to the stigma of opioid therapy and send a message to patients that these medications are inherently dangerous.”

Dr. Enzinger added that there are legitimate reasons why patients may not want to use opioids and that these should be respected. “But addiction risk should really not weigh into the decisions about pain management for patients who are dying from cancer,” she said.
 

Decline in opioid dose and prescriptions

Dr. Enzinger and colleagues used administrative data from the Centers for Medicare & Medicaid Services to identify 270,632 Medicare fee-for-service patients who had cancers that were associated with poor prognoses and who died from 2007 to 2017. During this period, the opioid crisis was first recognized. There followed legislative reforms and subsequent declines in population-based opioid prescribing.

Among the patients in the study, the most common cancers were lung, colorectal, pancreatic, prostate, and breast cancers; 166,962 patients (61.7%) were enrolled in hospice before death. This percentage increased from 57.1% in 2007 to 66.2% in 2017 (P for trend < .001).

From 2007 to 2017, the proportion of patients filling greater than or equal to 1 opioid prescriptions declined from 42.0% to 35.5%. The proportion declined faster from 2012-2017 than from 2007-2011.

The proportion of patients who filled prescriptions for long-acting opioids dropped from 18.1% to 11.5%. Here again, the decline was faster from 2012-2017 than from 2007-2011. Prescriptions for strong short-acting opioids declined from 31.7% to 28.5%. Prescribing was initially stable from 2007-2011 and began to decline in 2012. Conversely, prescriptions for weak short-acting opioids dropped from 8.4% to 6.5% from 2007-2011 and then stabilized after 2012.

The mean daily dose fell 24.5%, from 85.6 morphine milligram equivalents per day (MMED) to 64.6 MMED. Overall, the total amount of opioids prescribed per decedent fell 38.0%, from 1,075 MMEs per person to 666 MMEs.

At the same time, the proportion of patients who visited EDs increased 50.8%, from 13.2% to 19.9%.
 

Experts weigh in

Approached for an independent comment, Amit Barochia, MD, a hematologist/oncologist with Health First Medical Group, Titusville, Fla., commented that the decline could be due, in part, to greater vigilance and awareness by physicians in light of more stringent requirements and of federal and state regulations. “Some physicians are avoiding prescribing opioids due to more regulations and requirements as well, which is routing patients to the ER for pain relief,” he said.

Dr. Barochia agreed that some of the decline could be due to patient factors. “I do think that some of the patients are hesitant about considering opioid use for better pain relief, in part due to fear of addiction as well as complications arising from their use,” he said. “This is likely resulting from more awareness in the community about their adverse effects.

“That awareness could come from aggressive media coverage as well as social media,” he continued. “It is also true that there is a difficulty in getting authorization for certain opioid products, which is delaying the onset of a proper pain regimen that would help to provide adequate pain relief early on.”

For patients with advanced cancer, earlier referral to palliative care would be beneficial, Dr. Barochia pointed out, because this would allow for a more in-depth discussion about pain in addition to addressing the physical and mental symptoms associated with cancer.

Fox Chase Cancer Center’s Dr. Chwistek noted that patients and their caregivers are often apprehensive about the potential adverse effects of opioids, because they often hear about community-based opioid overdoses and are fearful of taking the medications. “Additionally, it has become increasingly challenging to fill opioid prescriptions at local pharmacies, due to quantity limitations, ubiquitous need for prior authorizations, and stigma,” he said.

The fear of addiction is often brought up by the patients during clinic visits, and insurers and pharmacies have imposed many limits on opioid prescribing. “Most of these can be overcome with prior authorizations, but not always, and prior authorizations are time consuming, confusing, and very frustrating for patients,” he said in an interview.

These findings suggest that not enough patients are getting optimal palliative care. “One of the primary tenets of palliative care is optimal symptom control, including pain,” said Dr. Chwistek. “Palliative care teams have the experience and insight needed to help patients overcome the barriers to appropriate pain control. Education, support, and advocacy are critical to ensure that patients’ pain is appropriately addressed.”

The study was funded by a grant from the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services.

A version of this article first appeared on Medscape.com.

Terminally ill patients with advanced cancer may not be receiving adequate pain management, according to new findings.

There has been a sharp decrease in access to opioids during the past decade, and many patients are going to emergency departments for pain treatment.

Overall, during the study period (2007-2017), there was a 34% reduction in the number of opioid prescriptions filled per patient and a 38% reduction in the total dose of opioids filled near the end of life.

There was a dramatic drop in the use of long-acting opioids, which can provide patients with more consistent pain relief and are important for managing severe cancer pain. The investigators’ results show that during the study period, the number of long-acting opioid prescriptions filled per patient fell by 50%.

“We do believe that the decline in cancer patients’ access to opioids near the end of life is likely attributable to the efforts to curtail opioid misuse,” commented lead author Andrea Enzinger, MD, a medical oncologist at Dana-Farber Cancer Institute, Boston.

The study was published online July 22 in the Journal of Clinical Oncology.

“The study provides fascinating data that support our clinical observations,” said Marcin Chwistek, MD, FAAHPM, director of the supportive oncology and palliative care program at Fox Chase Cancer Center, Philadelphia, who was asked for comment. “Primarily, we have noticed a heightened reluctance on the parts of patients with cancer, including those with advanced cancer, to take opioids in general.”
 

Many factors involved

The crisis of opioid misuse and abuse led to the implementation of regulations to curb inappropriate prescribing. But these restrictions on opioid prescribing may have unintended consequences for patients with advanced, incurable malignancies who are experiencing pain.

“Many but not all opioid regulations specifically exclude cancer patients,” said Dr. Enzinger. “However, the cumulative effect of these regulations may have had a chilling effect on providers’ comfort or willingness to prescribe opioids, even for cancer pain.”

She said in an interview that the prescribing of opioids has become much more difficult. Prescribers are often required to sign an opioid agreement with patients prior to providing them with opioids. Health care professionals may need to use a two-factor authentication to prescribe, and prescribers in 49 of 50 U.S. states are required to check electronic prescription drug monitoring programs prior to providing the prescription.

“After the medications are prescribed, insurance companies require prior-authorization paperwork before filling the medications, particularly for long-acting opioids or high-dose opioids,” Dr. Enzinger said. “These barriers pile up and make the whole process onerous and time consuming.”

Patient factors may also have contributed to the decline in use.

“Cancer patients are often very hesitant to use opioids to treat their pain, as they worry about becoming addicted or being labeled a ‘pill seeker,’” she explained. “Also, the added regulations, such as requirements for prior authorization paperwork, signing opioid agreements, and so on, may add to the stigma of opioid therapy and send a message to patients that these medications are inherently dangerous.”

Dr. Enzinger added that there are legitimate reasons why patients may not want to use opioids and that these should be respected. “But addiction risk should really not weigh into the decisions about pain management for patients who are dying from cancer,” she said.
 

Decline in opioid dose and prescriptions

Dr. Enzinger and colleagues used administrative data from the Centers for Medicare & Medicaid Services to identify 270,632 Medicare fee-for-service patients who had cancers that were associated with poor prognoses and who died from 2007 to 2017. During this period, the opioid crisis was first recognized. There followed legislative reforms and subsequent declines in population-based opioid prescribing.

Among the patients in the study, the most common cancers were lung, colorectal, pancreatic, prostate, and breast cancers; 166,962 patients (61.7%) were enrolled in hospice before death. This percentage increased from 57.1% in 2007 to 66.2% in 2017 (P for trend < .001).

From 2007 to 2017, the proportion of patients filling greater than or equal to 1 opioid prescriptions declined from 42.0% to 35.5%. The proportion declined faster from 2012-2017 than from 2007-2011.

The proportion of patients who filled prescriptions for long-acting opioids dropped from 18.1% to 11.5%. Here again, the decline was faster from 2012-2017 than from 2007-2011. Prescriptions for strong short-acting opioids declined from 31.7% to 28.5%. Prescribing was initially stable from 2007-2011 and began to decline in 2012. Conversely, prescriptions for weak short-acting opioids dropped from 8.4% to 6.5% from 2007-2011 and then stabilized after 2012.

The mean daily dose fell 24.5%, from 85.6 morphine milligram equivalents per day (MMED) to 64.6 MMED. Overall, the total amount of opioids prescribed per decedent fell 38.0%, from 1,075 MMEs per person to 666 MMEs.

At the same time, the proportion of patients who visited EDs increased 50.8%, from 13.2% to 19.9%.
 

Experts weigh in

Approached for an independent comment, Amit Barochia, MD, a hematologist/oncologist with Health First Medical Group, Titusville, Fla., commented that the decline could be due, in part, to greater vigilance and awareness by physicians in light of more stringent requirements and of federal and state regulations. “Some physicians are avoiding prescribing opioids due to more regulations and requirements as well, which is routing patients to the ER for pain relief,” he said.

Dr. Barochia agreed that some of the decline could be due to patient factors. “I do think that some of the patients are hesitant about considering opioid use for better pain relief, in part due to fear of addiction as well as complications arising from their use,” he said. “This is likely resulting from more awareness in the community about their adverse effects.

“That awareness could come from aggressive media coverage as well as social media,” he continued. “It is also true that there is a difficulty in getting authorization for certain opioid products, which is delaying the onset of a proper pain regimen that would help to provide adequate pain relief early on.”

For patients with advanced cancer, earlier referral to palliative care would be beneficial, Dr. Barochia pointed out, because this would allow for a more in-depth discussion about pain in addition to addressing the physical and mental symptoms associated with cancer.

Fox Chase Cancer Center’s Dr. Chwistek noted that patients and their caregivers are often apprehensive about the potential adverse effects of opioids, because they often hear about community-based opioid overdoses and are fearful of taking the medications. “Additionally, it has become increasingly challenging to fill opioid prescriptions at local pharmacies, due to quantity limitations, ubiquitous need for prior authorizations, and stigma,” he said.

The fear of addiction is often brought up by the patients during clinic visits, and insurers and pharmacies have imposed many limits on opioid prescribing. “Most of these can be overcome with prior authorizations, but not always, and prior authorizations are time consuming, confusing, and very frustrating for patients,” he said in an interview.

These findings suggest that not enough patients are getting optimal palliative care. “One of the primary tenets of palliative care is optimal symptom control, including pain,” said Dr. Chwistek. “Palliative care teams have the experience and insight needed to help patients overcome the barriers to appropriate pain control. Education, support, and advocacy are critical to ensure that patients’ pain is appropriately addressed.”

The study was funded by a grant from the Agency for Healthcare Research and Quality of the U.S. Department of Health and Human Services.

A version of this article first appeared on Medscape.com.

Although prostate cancer is the second most common cancer in men worldwide, it is not a lethal cancer: Improvements in early detection and treatment have boosted the 10-year relative survival rate to 98%.

But for many men, life after treatment is an ongoing struggle.

One of the first qualitative survey studies of long-term prostate cancer survivorship in Australia found that many survivors are living with adverse effects such as urinary incontinence and sexual dysfunction and that they continue to have heightened feelings of distress.

Many of the patients surveyed said that they had not received follow-up care and felt they had been “abandoned” by their health care professionals.

One man called it “the survivorship abyss.”

“As the prevalence of prostate cancer survivors continues to grow globally, the absence of integrated shared survivorship care models into clinical practice, such as survivorship care guidelines/plans and/or interventions, will perpetuate the sense of abandonment and the overwhelming burden of care of men lost in the PC [prostate cancer] ‘survivorship abyss,’” say the authors.

The report was published online in Psycho-Oncology.

“The good news is that more men than ever before are surviving prostate cancer,” commented lead author Carolyn G. Mazariego, PhD, a research fellow at the Daffodil Center of the Cancer Council New South Wales and the University of Sydney.

“As our population grows and ages, an increasing number of men are facing these survivorship challenges, and the need for clear survivorship care guidelines becomes increasingly vital,” Dr. Mazariego told this news organization.
 

Details of the survey findings

To find participants for their study, the team drew upon a cohort of 578 men who were included in the 15-year follow-up phase of the longitudinal New South Wales Prostate Cancer Care and Outcomes Study (PCOS).

The researchers interviewed 37 men for the study. The majority (88.6%) had been diagnosed with localized disease, and just over half (54%) had undergone radical prostatectomy as their primary treatment.

Some expressed regret over having had surgery. One respondent, a 15-year survivor, commented: “I really didn’t know how intrusive [surgery] was as far as losing the length of my penis and its functions. To this day, I sometimes can’t believe it’s happened. It’s devastating.”

The survey also found that most survivors viewed active treatment as the only way to avoid death.

In hindsight, some questioned whether radical treatment was necessary and whether they might have been better served by active surveillance.

Many said they were never given a chance to discuss sexual dysfunction, and others said their questions sparked an awkward, limited conversation. Many said they suffered in silence.

“We know that there is a sort of ‘cycle of silence’ between patients and health care providers about sexual issues, and that was particularly true for the men we spoke to,” Dr. Mazariego said. “This cycle of silence can stem from confusion and ambiguity as to who men should speak with regarding these ongoing issues.”

“It’s just like being part of a secret society,” said one survivor. “Like you don’t know about it until you’re in it ... I don’t think people want to know if they have it [prostate cancer] or want it known. It’s all hush hush.”

Prostate cancer patients often feel uncomfortable talking about sexual function, Dr. Mazariego pointed out. “Many men instead internalized these thoughts or concerns and just ‘got on’ with life.”

One survey participant said: “Well, you just gotta deal with it [issues relating to prostate cancer]. Just got to try and wipe out the thoughts, that’s all you can do. Suck it up and carry on.”
 

Discussions must be part of standard of care

Dr. Mazariego emphasized that for prostate cancer survivorship to improve, conversations about the psychosocial needs of patients must be normalized and made routine. Discussions about post-treatment side effects that cause functional impairments and are stressful to relationships must be embedded into the standards of care, she added. This will allow physicians to use these kinds of conversations “as a springboard for referrals to appropriate care.”

“Patients of all ages will have concerns related to sex and sexual function, whether you ask about them or not,” said Brad Zebrack, PhD, MSW, MPH, professor at the University of Michigan School of Social Work, Ann Arbor, who was approached for comment.

At the very least, physicians should be prepared to “acknowledge and describe possible effects of therapy on sex and sexual function and follow up by describing available supports for education and either individual or couples counseling,” said Dr. Zebrack, who is also a member of the health behavior and outcomes research program at the Rogel Cancer Center.

Physicians can also refer patients to evidence-based resources and toolkits, he said. He noted that Will2Love offers self-help programs for cancer-related sexual problems and is “an outstanding resource.”
 

Distress screening needed

Universal psychosocial distress screening is needed to identify men with prostate cancer who have high levels of distress, argues Jeff Dunn, AO, PhD, who is CEO of the Prostate Cancer Foundation of Australia (PCFA), in Sydney.

Without this, men will not seek help for their unmet needs, Dr. Dunn noted in a 2019 editorial in the European Journal of Cancer Care.

The unmet psychosocial needs of prostate cancer patients and their partners “are highly prevalent,” said Dr. Dunn and co-author Suzanne K. Chambers, AO, PhD, dean of the Faculty of Health at the University of Technology Sydney. “...[F]or many prostate cancer survivors, the physical, social, psychological and relationship challenges will be long term, if not lifelong,” they write.

Even in Australia, where 1 in every 6 men are expected to be diagnosed with prostate cancer by age 85, efforts to improve survivorship care have not produced the desired results, they note.

In 2019, the PCFA published a monograph in which the organization recommended routine distress screenings and referrals to evidence-based psychosocial care for prostate cancer survivors. The foundation predicted that it would be “a game-changer for every Australian man impacted by the disease.”

“Yet, we still do not have a national survivorship care plan for prostate cancer survivors in Australia,” Dr. Mazariego said.

Left untreated, the psychosocial effects of prostate cancer “are considerable and certainly factors that should be considered as a threat to well-being,” she emphasized.

“Certainly, accumulation of unmet psychosocial needs increases risks for depression and suicide, which is true in both cancer and noncancer populations,” said Dr. Zebrack.

Data back this up. One study of patients with prostate cancer found that after diagnosis, 1 in 4 experienced anxiety, and 1 in 5 experienced depression. Another study found that the risk for suicide was higher among men with prostate cancer during the first year after diagnosis than among men with other solid-organ malignancies.

More recently, a 2018 population-based Australian cohort study of men in New South Wales revealed that the risk for death by suicide was 70% higher among men who had been diagnosed with prostate cancer compared with men in the general population. This risk was higher within the first year following diagnosis and was higher in men with nonlocalized disease, those who were single, those who were living in a major city, and those who were unmarried.

Dr. Mazariego and the team reporting the survey found that men who received supportive care had a greater chance of reconciling living with functional impairments. “Receiving adequate survivorship care and trusting patient-clinician relationships appeared to be associated with greater resilience and positivity in the men’s acceptance of cancer-related, long-term challenges and personal limitations,” they note.
 

Developing postcancer identity

Survivors also appeared to have developed a post-cancer identity that was more invested in personal relationships or in taking a more active role in their own health.

“Treating my prostate cancer gave me a second chance,” said one survivor. “Yeah, I’m a survivor, but more importantly, I’m a loving husband now. I know I wasn’t as giving back then.”

Another man admitted that before his diagnosis, he never went to the doctor. “I go much more often now,” he said. “You need to check up on yourself, at least once a year. Could have caught the cancer earlier if I was doing that.”

These comments appear to be borne out by data released last year by the American Cancer Society (ACS), which found that the number of number of cancer-related suicides in the United States was on the decline, as reported by this news organization.

Some of the biggest decreases occurred in men with prostate cancer, although prostate cancer was associated with 15% of cancer-related suicides. Only lung cancer was associated with more cancer-related suicides, at 18%.

A factor in the decrease in cancer-related suicides was likely to be an increase in the use of supportive care services, the ACS researchers commented.

“Although no causal relationship can be established, our findings suggest an evolving role of psycho-oncology care and palliative and hospice care given the promotion and increased utilization of these services among cancer patients during this period,” they commented.

The study was funded by the Cancer Institute NSW. Dr. Mazariego and colleagues have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Although prostate cancer is the second most common cancer in men worldwide, it is not a lethal cancer: Improvements in early detection and treatment have boosted the 10-year relative survival rate to 98%.

But for many men, life after treatment is an ongoing struggle.

One of the first qualitative survey studies of long-term prostate cancer survivorship in Australia found that many survivors are living with adverse effects such as urinary incontinence and sexual dysfunction and that they continue to have heightened feelings of distress.

Many of the patients surveyed said that they had not received follow-up care and felt they had been “abandoned” by their health care professionals.

One man called it “the survivorship abyss.”

“As the prevalence of prostate cancer survivors continues to grow globally, the absence of integrated shared survivorship care models into clinical practice, such as survivorship care guidelines/plans and/or interventions, will perpetuate the sense of abandonment and the overwhelming burden of care of men lost in the PC [prostate cancer] ‘survivorship abyss,’” say the authors.

The report was published online in Psycho-Oncology.

“The good news is that more men than ever before are surviving prostate cancer,” commented lead author Carolyn G. Mazariego, PhD, a research fellow at the Daffodil Center of the Cancer Council New South Wales and the University of Sydney.

“As our population grows and ages, an increasing number of men are facing these survivorship challenges, and the need for clear survivorship care guidelines becomes increasingly vital,” Dr. Mazariego told this news organization.
 

Details of the survey findings

To find participants for their study, the team drew upon a cohort of 578 men who were included in the 15-year follow-up phase of the longitudinal New South Wales Prostate Cancer Care and Outcomes Study (PCOS).

The researchers interviewed 37 men for the study. The majority (88.6%) had been diagnosed with localized disease, and just over half (54%) had undergone radical prostatectomy as their primary treatment.

Some expressed regret over having had surgery. One respondent, a 15-year survivor, commented: “I really didn’t know how intrusive [surgery] was as far as losing the length of my penis and its functions. To this day, I sometimes can’t believe it’s happened. It’s devastating.”

The survey also found that most survivors viewed active treatment as the only way to avoid death.

In hindsight, some questioned whether radical treatment was necessary and whether they might have been better served by active surveillance.

Many said they were never given a chance to discuss sexual dysfunction, and others said their questions sparked an awkward, limited conversation. Many said they suffered in silence.

“We know that there is a sort of ‘cycle of silence’ between patients and health care providers about sexual issues, and that was particularly true for the men we spoke to,” Dr. Mazariego said. “This cycle of silence can stem from confusion and ambiguity as to who men should speak with regarding these ongoing issues.”

“It’s just like being part of a secret society,” said one survivor. “Like you don’t know about it until you’re in it ... I don’t think people want to know if they have it [prostate cancer] or want it known. It’s all hush hush.”

Prostate cancer patients often feel uncomfortable talking about sexual function, Dr. Mazariego pointed out. “Many men instead internalized these thoughts or concerns and just ‘got on’ with life.”

One survey participant said: “Well, you just gotta deal with it [issues relating to prostate cancer]. Just got to try and wipe out the thoughts, that’s all you can do. Suck it up and carry on.”
 

Discussions must be part of standard of care

Dr. Mazariego emphasized that for prostate cancer survivorship to improve, conversations about the psychosocial needs of patients must be normalized and made routine. Discussions about post-treatment side effects that cause functional impairments and are stressful to relationships must be embedded into the standards of care, she added. This will allow physicians to use these kinds of conversations “as a springboard for referrals to appropriate care.”

“Patients of all ages will have concerns related to sex and sexual function, whether you ask about them or not,” said Brad Zebrack, PhD, MSW, MPH, professor at the University of Michigan School of Social Work, Ann Arbor, who was approached for comment.

At the very least, physicians should be prepared to “acknowledge and describe possible effects of therapy on sex and sexual function and follow up by describing available supports for education and either individual or couples counseling,” said Dr. Zebrack, who is also a member of the health behavior and outcomes research program at the Rogel Cancer Center.

Physicians can also refer patients to evidence-based resources and toolkits, he said. He noted that Will2Love offers self-help programs for cancer-related sexual problems and is “an outstanding resource.”
 

Distress screening needed

Universal psychosocial distress screening is needed to identify men with prostate cancer who have high levels of distress, argues Jeff Dunn, AO, PhD, who is CEO of the Prostate Cancer Foundation of Australia (PCFA), in Sydney.

Without this, men will not seek help for their unmet needs, Dr. Dunn noted in a 2019 editorial in the European Journal of Cancer Care.

The unmet psychosocial needs of prostate cancer patients and their partners “are highly prevalent,” said Dr. Dunn and co-author Suzanne K. Chambers, AO, PhD, dean of the Faculty of Health at the University of Technology Sydney. “...[F]or many prostate cancer survivors, the physical, social, psychological and relationship challenges will be long term, if not lifelong,” they write.

Even in Australia, where 1 in every 6 men are expected to be diagnosed with prostate cancer by age 85, efforts to improve survivorship care have not produced the desired results, they note.

In 2019, the PCFA published a monograph in which the organization recommended routine distress screenings and referrals to evidence-based psychosocial care for prostate cancer survivors. The foundation predicted that it would be “a game-changer for every Australian man impacted by the disease.”

“Yet, we still do not have a national survivorship care plan for prostate cancer survivors in Australia,” Dr. Mazariego said.

Left untreated, the psychosocial effects of prostate cancer “are considerable and certainly factors that should be considered as a threat to well-being,” she emphasized.

“Certainly, accumulation of unmet psychosocial needs increases risks for depression and suicide, which is true in both cancer and noncancer populations,” said Dr. Zebrack.

Data back this up. One study of patients with prostate cancer found that after diagnosis, 1 in 4 experienced anxiety, and 1 in 5 experienced depression. Another study found that the risk for suicide was higher among men with prostate cancer during the first year after diagnosis than among men with other solid-organ malignancies.

More recently, a 2018 population-based Australian cohort study of men in New South Wales revealed that the risk for death by suicide was 70% higher among men who had been diagnosed with prostate cancer compared with men in the general population. This risk was higher within the first year following diagnosis and was higher in men with nonlocalized disease, those who were single, those who were living in a major city, and those who were unmarried.

Dr. Mazariego and the team reporting the survey found that men who received supportive care had a greater chance of reconciling living with functional impairments. “Receiving adequate survivorship care and trusting patient-clinician relationships appeared to be associated with greater resilience and positivity in the men’s acceptance of cancer-related, long-term challenges and personal limitations,” they note.
 

Developing postcancer identity

Survivors also appeared to have developed a post-cancer identity that was more invested in personal relationships or in taking a more active role in their own health.

“Treating my prostate cancer gave me a second chance,” said one survivor. “Yeah, I’m a survivor, but more importantly, I’m a loving husband now. I know I wasn’t as giving back then.”

Another man admitted that before his diagnosis, he never went to the doctor. “I go much more often now,” he said. “You need to check up on yourself, at least once a year. Could have caught the cancer earlier if I was doing that.”

These comments appear to be borne out by data released last year by the American Cancer Society (ACS), which found that the number of number of cancer-related suicides in the United States was on the decline, as reported by this news organization.

Some of the biggest decreases occurred in men with prostate cancer, although prostate cancer was associated with 15% of cancer-related suicides. Only lung cancer was associated with more cancer-related suicides, at 18%.

A factor in the decrease in cancer-related suicides was likely to be an increase in the use of supportive care services, the ACS researchers commented.

“Although no causal relationship can be established, our findings suggest an evolving role of psycho-oncology care and palliative and hospice care given the promotion and increased utilization of these services among cancer patients during this period,” they commented.

The study was funded by the Cancer Institute NSW. Dr. Mazariego and colleagues have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Although prostate cancer is the second most common cancer in men worldwide, it is not a lethal cancer: Improvements in early detection and treatment have boosted the 10-year relative survival rate to 98%.

But for many men, life after treatment is an ongoing struggle.

One of the first qualitative survey studies of long-term prostate cancer survivorship in Australia found that many survivors are living with adverse effects such as urinary incontinence and sexual dysfunction and that they continue to have heightened feelings of distress.

Many of the patients surveyed said that they had not received follow-up care and felt they had been “abandoned” by their health care professionals.

One man called it “the survivorship abyss.”

“As the prevalence of prostate cancer survivors continues to grow globally, the absence of integrated shared survivorship care models into clinical practice, such as survivorship care guidelines/plans and/or interventions, will perpetuate the sense of abandonment and the overwhelming burden of care of men lost in the PC [prostate cancer] ‘survivorship abyss,’” say the authors.

The report was published online in Psycho-Oncology.

“The good news is that more men than ever before are surviving prostate cancer,” commented lead author Carolyn G. Mazariego, PhD, a research fellow at the Daffodil Center of the Cancer Council New South Wales and the University of Sydney.

“As our population grows and ages, an increasing number of men are facing these survivorship challenges, and the need for clear survivorship care guidelines becomes increasingly vital,” Dr. Mazariego told this news organization.
 

Details of the survey findings

To find participants for their study, the team drew upon a cohort of 578 men who were included in the 15-year follow-up phase of the longitudinal New South Wales Prostate Cancer Care and Outcomes Study (PCOS).

The researchers interviewed 37 men for the study. The majority (88.6%) had been diagnosed with localized disease, and just over half (54%) had undergone radical prostatectomy as their primary treatment.

Some expressed regret over having had surgery. One respondent, a 15-year survivor, commented: “I really didn’t know how intrusive [surgery] was as far as losing the length of my penis and its functions. To this day, I sometimes can’t believe it’s happened. It’s devastating.”

The survey also found that most survivors viewed active treatment as the only way to avoid death.

In hindsight, some questioned whether radical treatment was necessary and whether they might have been better served by active surveillance.

Many said they were never given a chance to discuss sexual dysfunction, and others said their questions sparked an awkward, limited conversation. Many said they suffered in silence.

“We know that there is a sort of ‘cycle of silence’ between patients and health care providers about sexual issues, and that was particularly true for the men we spoke to,” Dr. Mazariego said. “This cycle of silence can stem from confusion and ambiguity as to who men should speak with regarding these ongoing issues.”

“It’s just like being part of a secret society,” said one survivor. “Like you don’t know about it until you’re in it ... I don’t think people want to know if they have it [prostate cancer] or want it known. It’s all hush hush.”

Prostate cancer patients often feel uncomfortable talking about sexual function, Dr. Mazariego pointed out. “Many men instead internalized these thoughts or concerns and just ‘got on’ with life.”

One survey participant said: “Well, you just gotta deal with it [issues relating to prostate cancer]. Just got to try and wipe out the thoughts, that’s all you can do. Suck it up and carry on.”
 

Discussions must be part of standard of care

Dr. Mazariego emphasized that for prostate cancer survivorship to improve, conversations about the psychosocial needs of patients must be normalized and made routine. Discussions about post-treatment side effects that cause functional impairments and are stressful to relationships must be embedded into the standards of care, she added. This will allow physicians to use these kinds of conversations “as a springboard for referrals to appropriate care.”

“Patients of all ages will have concerns related to sex and sexual function, whether you ask about them or not,” said Brad Zebrack, PhD, MSW, MPH, professor at the University of Michigan School of Social Work, Ann Arbor, who was approached for comment.

At the very least, physicians should be prepared to “acknowledge and describe possible effects of therapy on sex and sexual function and follow up by describing available supports for education and either individual or couples counseling,” said Dr. Zebrack, who is also a member of the health behavior and outcomes research program at the Rogel Cancer Center.

Physicians can also refer patients to evidence-based resources and toolkits, he said. He noted that Will2Love offers self-help programs for cancer-related sexual problems and is “an outstanding resource.”
 

Distress screening needed

Universal psychosocial distress screening is needed to identify men with prostate cancer who have high levels of distress, argues Jeff Dunn, AO, PhD, who is CEO of the Prostate Cancer Foundation of Australia (PCFA), in Sydney.

Without this, men will not seek help for their unmet needs, Dr. Dunn noted in a 2019 editorial in the European Journal of Cancer Care.

The unmet psychosocial needs of prostate cancer patients and their partners “are highly prevalent,” said Dr. Dunn and co-author Suzanne K. Chambers, AO, PhD, dean of the Faculty of Health at the University of Technology Sydney. “...[F]or many prostate cancer survivors, the physical, social, psychological and relationship challenges will be long term, if not lifelong,” they write.

Even in Australia, where 1 in every 6 men are expected to be diagnosed with prostate cancer by age 85, efforts to improve survivorship care have not produced the desired results, they note.

In 2019, the PCFA published a monograph in which the organization recommended routine distress screenings and referrals to evidence-based psychosocial care for prostate cancer survivors. The foundation predicted that it would be “a game-changer for every Australian man impacted by the disease.”

“Yet, we still do not have a national survivorship care plan for prostate cancer survivors in Australia,” Dr. Mazariego said.

Left untreated, the psychosocial effects of prostate cancer “are considerable and certainly factors that should be considered as a threat to well-being,” she emphasized.

“Certainly, accumulation of unmet psychosocial needs increases risks for depression and suicide, which is true in both cancer and noncancer populations,” said Dr. Zebrack.

Data back this up. One study of patients with prostate cancer found that after diagnosis, 1 in 4 experienced anxiety, and 1 in 5 experienced depression. Another study found that the risk for suicide was higher among men with prostate cancer during the first year after diagnosis than among men with other solid-organ malignancies.

More recently, a 2018 population-based Australian cohort study of men in New South Wales revealed that the risk for death by suicide was 70% higher among men who had been diagnosed with prostate cancer compared with men in the general population. This risk was higher within the first year following diagnosis and was higher in men with nonlocalized disease, those who were single, those who were living in a major city, and those who were unmarried.

Dr. Mazariego and the team reporting the survey found that men who received supportive care had a greater chance of reconciling living with functional impairments. “Receiving adequate survivorship care and trusting patient-clinician relationships appeared to be associated with greater resilience and positivity in the men’s acceptance of cancer-related, long-term challenges and personal limitations,” they note.
 

Developing postcancer identity

Survivors also appeared to have developed a post-cancer identity that was more invested in personal relationships or in taking a more active role in their own health.

“Treating my prostate cancer gave me a second chance,” said one survivor. “Yeah, I’m a survivor, but more importantly, I’m a loving husband now. I know I wasn’t as giving back then.”

Another man admitted that before his diagnosis, he never went to the doctor. “I go much more often now,” he said. “You need to check up on yourself, at least once a year. Could have caught the cancer earlier if I was doing that.”

These comments appear to be borne out by data released last year by the American Cancer Society (ACS), which found that the number of number of cancer-related suicides in the United States was on the decline, as reported by this news organization.

Some of the biggest decreases occurred in men with prostate cancer, although prostate cancer was associated with 15% of cancer-related suicides. Only lung cancer was associated with more cancer-related suicides, at 18%.

A factor in the decrease in cancer-related suicides was likely to be an increase in the use of supportive care services, the ACS researchers commented.

“Although no causal relationship can be established, our findings suggest an evolving role of psycho-oncology care and palliative and hospice care given the promotion and increased utilization of these services among cancer patients during this period,” they commented.

The study was funded by the Cancer Institute NSW. Dr. Mazariego and colleagues have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Survivors of childhood cancers are at increased risk for prescription opioid misuse compared with their peers, a review of a claims database revealed.

Among more than 8,000 patients age 21 or younger who had completed treatment for hematologic, central nervous system, bone, or gonadal cancers, survivors were significantly more likely than were their peers to have an opioid prescription, longer duration of prescription, and higher daily doses of opioids, and to have opioid prescriptions overlapping for a week or more, reported Xu Ji, PhD, of Emory University in Atlanta.

Teenage and young adult patients were at higher risk than were patients younger than 12, and the risk was highest among patients who had been treated for bone malignancies, as well as those who had undergone any hematopoietic stem cell transplant.

“These findings suggest that health care providers who regularly see survivors should explore nonopioid options to help prevent opioid misuse, and screen for potential misuse in those who actually receive opioids,” she said in an oral abstract presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.

“This is a really important topic, and something that’s probably been underinvestigated and underexplored in our patient population,” said session comoderator Sheri Spunt, MD, Endowed Professor of Pediatric Cancer at Stanford (Calif.) University.
 

Database review

Dr. Ji and colleagues used the IBM MarketScan Commercial Claims and Encounters database from 2009 to 2018 to examine prescription opioid use, potential misuse, and substance use disorders in pediatric cancer survivors in the first year after completion of therapy, and to identify factors associated with risk for misuse or substance use disorders. Specifically, the period of interest was the first year after completion of all treatments, including surgery, chemotherapy, radiation, and stem cell transplant (Abstract 2015).

They looked at deidentified records on any opioid prescription and for treatment of any opioid use or substance use disorder (alcohol, psychotherapeutic drugs, marijuana, or illicit drug use disorders).

They defined indicators of potential misuse as either prescriptions for long-acting or extended-release opioids for acute pain conditions; opioid and benzodiazepine prescriptions overlapping by a week or more; opioid prescriptions overlapping by a week or more; high daily opioid dosage (prescribed daily dose of 100 or greater morphine milligram equivalent [MME]; and/or opioid dose escalation (an increase of at least 50% in mean MMEs per month twice consecutively within 1 year).

They compared outcomes between a total of 8,635 survivors and 44,175 controls, matched on a 1:5 basis with survivors by age, sex, and region, and continuous enrollment during the 1-year posttherapy period.

In each of three age categories – 0 to 11 years, 12 to 17 years, and 18 years and older – survivors were significantly more likely to have received an opioid prescription, at 15% for the youngest survivors vs. 2% of controls, 25% vs. 8% for 12- to 17-year-olds, and 28% vs. 12% for those 18 and older (P < .01 for all three comparisons).

Survivors were also significantly more likely to have any indicator of potential misuse (1.6% vs. 0.1%, 4.6% vs. 0.5%, and 7.4% vs. 1.2%, respectively, P < .001 for all) and both the youngest and oldest groups (but not 12- to 17-year-olds) were significantly more like to have opioid or substance use disorder (0.4% vs. 0% for 0-11 years, 5.76% vs. 4.2% for 18 years and older, P < .001 for both).

Among patients with any opioid prescription, survivors were significantly more likely than were controls of any age to have indicators for potential misuse. For example, 13% of survivors aged 18 years and older had prescriptions for high opioid doses, compared with 5% of controls, and 12% had prescription overlap, vs. 2%.

Compared with patients with leukemia, patients treated for bone malignancies had a 6% greater risk for having any indicator of misuse, while patients with other malignancies were at slightly lower risk for misuse than those who completed leukemia therapy.

Patients who received any stem cell transplant had an 8.4% greater risk for misuse compared with patients who had surgery only.
 

Opioids pre- and posttreatment?

“Being someone who takes care of a lot of bone cancer patients, I do see patients with these issues,” Dr. Spunt said.

Audience member Jack H. Staddon, MD, PhD, of the Billings (Montana) Clinic, noted the possibility that opioid use during treatment may have been carried on into the posttreatment period, and asked whether use of narcotics during treatment was an independent risk factor for posttreatment narcotic use or misuse.

The researchers plan to investigate this question in future studies, Dr. Ji replied.

They did not report a study funding source. Dr. Ji and coauthors and Dr. Staddon reported no relevant disclosures.

Survivors of childhood cancers are at increased risk for prescription opioid misuse compared with their peers, a review of a claims database revealed.

Among more than 8,000 patients age 21 or younger who had completed treatment for hematologic, central nervous system, bone, or gonadal cancers, survivors were significantly more likely than were their peers to have an opioid prescription, longer duration of prescription, and higher daily doses of opioids, and to have opioid prescriptions overlapping for a week or more, reported Xu Ji, PhD, of Emory University in Atlanta.

Teenage and young adult patients were at higher risk than were patients younger than 12, and the risk was highest among patients who had been treated for bone malignancies, as well as those who had undergone any hematopoietic stem cell transplant.

“These findings suggest that health care providers who regularly see survivors should explore nonopioid options to help prevent opioid misuse, and screen for potential misuse in those who actually receive opioids,” she said in an oral abstract presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.

“This is a really important topic, and something that’s probably been underinvestigated and underexplored in our patient population,” said session comoderator Sheri Spunt, MD, Endowed Professor of Pediatric Cancer at Stanford (Calif.) University.
 

Database review

Dr. Ji and colleagues used the IBM MarketScan Commercial Claims and Encounters database from 2009 to 2018 to examine prescription opioid use, potential misuse, and substance use disorders in pediatric cancer survivors in the first year after completion of therapy, and to identify factors associated with risk for misuse or substance use disorders. Specifically, the period of interest was the first year after completion of all treatments, including surgery, chemotherapy, radiation, and stem cell transplant (Abstract 2015).

They looked at deidentified records on any opioid prescription and for treatment of any opioid use or substance use disorder (alcohol, psychotherapeutic drugs, marijuana, or illicit drug use disorders).

They defined indicators of potential misuse as either prescriptions for long-acting or extended-release opioids for acute pain conditions; opioid and benzodiazepine prescriptions overlapping by a week or more; opioid prescriptions overlapping by a week or more; high daily opioid dosage (prescribed daily dose of 100 or greater morphine milligram equivalent [MME]; and/or opioid dose escalation (an increase of at least 50% in mean MMEs per month twice consecutively within 1 year).

They compared outcomes between a total of 8,635 survivors and 44,175 controls, matched on a 1:5 basis with survivors by age, sex, and region, and continuous enrollment during the 1-year posttherapy period.

In each of three age categories – 0 to 11 years, 12 to 17 years, and 18 years and older – survivors were significantly more likely to have received an opioid prescription, at 15% for the youngest survivors vs. 2% of controls, 25% vs. 8% for 12- to 17-year-olds, and 28% vs. 12% for those 18 and older (P < .01 for all three comparisons).

Survivors were also significantly more likely to have any indicator of potential misuse (1.6% vs. 0.1%, 4.6% vs. 0.5%, and 7.4% vs. 1.2%, respectively, P < .001 for all) and both the youngest and oldest groups (but not 12- to 17-year-olds) were significantly more like to have opioid or substance use disorder (0.4% vs. 0% for 0-11 years, 5.76% vs. 4.2% for 18 years and older, P < .001 for both).

Among patients with any opioid prescription, survivors were significantly more likely than were controls of any age to have indicators for potential misuse. For example, 13% of survivors aged 18 years and older had prescriptions for high opioid doses, compared with 5% of controls, and 12% had prescription overlap, vs. 2%.

Compared with patients with leukemia, patients treated for bone malignancies had a 6% greater risk for having any indicator of misuse, while patients with other malignancies were at slightly lower risk for misuse than those who completed leukemia therapy.

Patients who received any stem cell transplant had an 8.4% greater risk for misuse compared with patients who had surgery only.
 

Opioids pre- and posttreatment?

“Being someone who takes care of a lot of bone cancer patients, I do see patients with these issues,” Dr. Spunt said.

Audience member Jack H. Staddon, MD, PhD, of the Billings (Montana) Clinic, noted the possibility that opioid use during treatment may have been carried on into the posttreatment period, and asked whether use of narcotics during treatment was an independent risk factor for posttreatment narcotic use or misuse.

The researchers plan to investigate this question in future studies, Dr. Ji replied.

They did not report a study funding source. Dr. Ji and coauthors and Dr. Staddon reported no relevant disclosures.

Survivors of childhood cancers are at increased risk for prescription opioid misuse compared with their peers, a review of a claims database revealed.

Among more than 8,000 patients age 21 or younger who had completed treatment for hematologic, central nervous system, bone, or gonadal cancers, survivors were significantly more likely than were their peers to have an opioid prescription, longer duration of prescription, and higher daily doses of opioids, and to have opioid prescriptions overlapping for a week or more, reported Xu Ji, PhD, of Emory University in Atlanta.

Teenage and young adult patients were at higher risk than were patients younger than 12, and the risk was highest among patients who had been treated for bone malignancies, as well as those who had undergone any hematopoietic stem cell transplant.

“These findings suggest that health care providers who regularly see survivors should explore nonopioid options to help prevent opioid misuse, and screen for potential misuse in those who actually receive opioids,” she said in an oral abstract presented during the annual meeting of the American Society of Pediatric Hematology/Oncology.

“This is a really important topic, and something that’s probably been underinvestigated and underexplored in our patient population,” said session comoderator Sheri Spunt, MD, Endowed Professor of Pediatric Cancer at Stanford (Calif.) University.
 

Database review

Dr. Ji and colleagues used the IBM MarketScan Commercial Claims and Encounters database from 2009 to 2018 to examine prescription opioid use, potential misuse, and substance use disorders in pediatric cancer survivors in the first year after completion of therapy, and to identify factors associated with risk for misuse or substance use disorders. Specifically, the period of interest was the first year after completion of all treatments, including surgery, chemotherapy, radiation, and stem cell transplant (Abstract 2015).

They looked at deidentified records on any opioid prescription and for treatment of any opioid use or substance use disorder (alcohol, psychotherapeutic drugs, marijuana, or illicit drug use disorders).

They defined indicators of potential misuse as either prescriptions for long-acting or extended-release opioids for acute pain conditions; opioid and benzodiazepine prescriptions overlapping by a week or more; opioid prescriptions overlapping by a week or more; high daily opioid dosage (prescribed daily dose of 100 or greater morphine milligram equivalent [MME]; and/or opioid dose escalation (an increase of at least 50% in mean MMEs per month twice consecutively within 1 year).

They compared outcomes between a total of 8,635 survivors and 44,175 controls, matched on a 1:5 basis with survivors by age, sex, and region, and continuous enrollment during the 1-year posttherapy period.

In each of three age categories – 0 to 11 years, 12 to 17 years, and 18 years and older – survivors were significantly more likely to have received an opioid prescription, at 15% for the youngest survivors vs. 2% of controls, 25% vs. 8% for 12- to 17-year-olds, and 28% vs. 12% for those 18 and older (P < .01 for all three comparisons).

Survivors were also significantly more likely to have any indicator of potential misuse (1.6% vs. 0.1%, 4.6% vs. 0.5%, and 7.4% vs. 1.2%, respectively, P < .001 for all) and both the youngest and oldest groups (but not 12- to 17-year-olds) were significantly more like to have opioid or substance use disorder (0.4% vs. 0% for 0-11 years, 5.76% vs. 4.2% for 18 years and older, P < .001 for both).

Among patients with any opioid prescription, survivors were significantly more likely than were controls of any age to have indicators for potential misuse. For example, 13% of survivors aged 18 years and older had prescriptions for high opioid doses, compared with 5% of controls, and 12% had prescription overlap, vs. 2%.

Compared with patients with leukemia, patients treated for bone malignancies had a 6% greater risk for having any indicator of misuse, while patients with other malignancies were at slightly lower risk for misuse than those who completed leukemia therapy.

Patients who received any stem cell transplant had an 8.4% greater risk for misuse compared with patients who had surgery only.
 

Opioids pre- and posttreatment?

“Being someone who takes care of a lot of bone cancer patients, I do see patients with these issues,” Dr. Spunt said.

Audience member Jack H. Staddon, MD, PhD, of the Billings (Montana) Clinic, noted the possibility that opioid use during treatment may have been carried on into the posttreatment period, and asked whether use of narcotics during treatment was an independent risk factor for posttreatment narcotic use or misuse.

The researchers plan to investigate this question in future studies, Dr. Ji replied.

They did not report a study funding source. Dr. Ji and coauthors and Dr. Staddon reported no relevant disclosures.

Sharing their personal experiences on social media can emphasize oncologists’ humanity and have substantive, beneficial effects on patient care, according to a presentation at the Collaboration for Outcomes using Social Media in Oncology (COSMO) inaugural meeting.

Mark A. Lewis, MD, explained to the COSMO meeting audience how storytelling on social media can educate and engage patients, advocates, and professional colleagues – advancing knowledge, dispelling misinformation, and promoting clinical research.

Dr. Lewis, an oncologist at Intermountain Healthcare in Salt Lake City, reflected on the bifid roles of oncologists as scientists engaged in life-long learning and humanists who can internalize and appreciate the unique character and circumstances of their patients.

Patients who have serious illnesses are necessarily aggregated by statistics. However, in an essay published in 2011, Dr. Lewis noted that “each individual patient partakes in a unique, irreproducible experiment where n = 1” (J Clin Oncol. 2011 Aug 1;29[22]:3103-4).

Dr. Lewis highlighted the duality of individual data points on a survival curve as descriptors of common disease trajectories and treatment effects. However, those data points also conceal important narratives regarding the most highly valued aspects of the doctor-patient relationship and the impact of cancer treatment on patients’ lives.

In referring to the futuristic essay “Ars Brevis,” Dr. Lewis contrasted the humanism of oncology specialists in the present day with the fictional image of data-regurgitating robots programmed to maximize the efficiency of each patient encounter (J Clin Oncol. 2013 May 10;31[14]:1792-4).

Dr. Lewis reminded attendees that to practice medicine without using both “head and heart” undermines the inherent nature of medical care.

Unfortunately, that perspective may not match the public perception of oncologists. Dr. Lewis described his experience of typing “oncologists are” into an Internet search engine and seeing the auto-complete function prompt words such as “criminals,” “evil,” “murderers,” and “confused.”

Obviously, it is hard to establish a trusting patient-doctor relationship if that is the prima facie perception of the oncology specialty.
 

Dispelling myths and creating community via social media

A primary goal of consultation with a newly-diagnosed cancer patient is for the patient to feel that the oncologist will be there to take care of them, regardless of what the future holds.

Dr. Lewis has found that social media can potentially extend that feeling to a global community of patients, caregivers, and others seeking information relevant to a cancer diagnosis. He believes that oncologists have an opportunity to dispel myths and fears by being attentive to the real-life concerns of patients.

Dr. Lewis took advantage of this opportunity when he underwent a Whipple procedure (pancreaticoduodenectomy) for a pancreatic neuroendocrine tumor. He and the hospital’s media services staff “live-tweeted” his surgery and recovery.

With those tweets, Dr. Lewis demystified each step of a major surgical procedure. From messages he received on social media, Dr. Lewis knows he made the decision to have a Whipple procedure more acceptable to other patients.

His personal medical experience notwithstanding, Dr. Lewis acknowledged that every patient’s circumstances are unique.

Oncologists cannot possibly empathize with every circumstance. However, when they show sensitivity to personal elements of the cancer experience, they shed light on the complicated role they play in patient care and can facilitate good decision-making among patients across the globe.
 

Social media for professional development and patient care

The publication of his 2011 essay was gratifying for Dr. Lewis, but the finite number of comments he received thereafter illustrated the rather limited audience that traditional academic publications have and the laborious process for subsequent interaction (J Clin Oncol. 2011 Aug 1;29[22]:3103-4).

First as an observer and later as a participant on social media, Dr. Lewis appreciated that teaching points and publications can be amplified by global distribution and the potential for informal bidirectional communication.

Social media platforms enable physicians to connect with a larger audience through participative communication, in which users develop, share, and react to content (N Engl J Med. 2009 Aug 13;361[7]:649-51).

Dr. Lewis reflected on how oncologists are challenged to sort through the thousands of oncology-focused publications annually. Through social media, one can see the studies on which the experts are commenting and appreciate the nuances that contextualize the results. Focused interactions with renowned doctors, at regular intervals, require little formality.

Online journal clubs enable the sharing of ideas, opinions, multimedia resources, and references across institutional and international borders (J Gen Intern Med. 2014 Oct;29[10]:1317-8).
 

Social media in oncology: Accomplishments and promise

The development of broadband Internet, wireless connectivity, and social media for peer-to-peer and general communication are among the major technological advances that have transformed medical communication.

As an organization, COSMO aims to describe, understand, and improve the use of social media to increase the penetration of evidence-based guidelines and research insights into clinical practice (Future Oncol. 2017 Jun;13[15]:1281-5).

At the inaugural COSMO meeting, areas of progress since COSMO’s inception in 2015 were highlighted, including:

• The involvement of cancer professionals and advocates in multiple distinctive platforms.
• The development of hashtag libraries to aggregate interest groups and topics.
• The refinement of strategies for engaging advocates with attention to inclusiveness.
• A steady trajectory of growth in tweeting at scientific conferences.

An overarching theme of the COSMO meeting was “authenticity,” a virtue that is easy to admire but requires conscious, consistent effort to achieve.

Disclosure of conflicts of interest and avoiding using social media simply as a recruitment tool for clinical trials are basic components of accurate self-representation.

In addition, Dr. Lewis advocated for sharing personal experiences in a component of social media posts so oncologists can show humanity as a feature of their professional online identity and inherent nature.

Dr. Lewis disclosed consultancy with Medscape/WebMD, which are owned by the same parent company as MDedge. He also disclosed relationships with Foundation Medicine, Natera, Exelixis, QED, HalioDX, and Ipsen.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Sharing their personal experiences on social media can emphasize oncologists’ humanity and have substantive, beneficial effects on patient care, according to a presentation at the Collaboration for Outcomes using Social Media in Oncology (COSMO) inaugural meeting.

Mark A. Lewis, MD, explained to the COSMO meeting audience how storytelling on social media can educate and engage patients, advocates, and professional colleagues – advancing knowledge, dispelling misinformation, and promoting clinical research.

Dr. Lewis, an oncologist at Intermountain Healthcare in Salt Lake City, reflected on the bifid roles of oncologists as scientists engaged in life-long learning and humanists who can internalize and appreciate the unique character and circumstances of their patients.

Patients who have serious illnesses are necessarily aggregated by statistics. However, in an essay published in 2011, Dr. Lewis noted that “each individual patient partakes in a unique, irreproducible experiment where n = 1” (J Clin Oncol. 2011 Aug 1;29[22]:3103-4).

Dr. Lewis highlighted the duality of individual data points on a survival curve as descriptors of common disease trajectories and treatment effects. However, those data points also conceal important narratives regarding the most highly valued aspects of the doctor-patient relationship and the impact of cancer treatment on patients’ lives.

In referring to the futuristic essay “Ars Brevis,” Dr. Lewis contrasted the humanism of oncology specialists in the present day with the fictional image of data-regurgitating robots programmed to maximize the efficiency of each patient encounter (J Clin Oncol. 2013 May 10;31[14]:1792-4).

Dr. Lewis reminded attendees that to practice medicine without using both “head and heart” undermines the inherent nature of medical care.

Unfortunately, that perspective may not match the public perception of oncologists. Dr. Lewis described his experience of typing “oncologists are” into an Internet search engine and seeing the auto-complete function prompt words such as “criminals,” “evil,” “murderers,” and “confused.”

Obviously, it is hard to establish a trusting patient-doctor relationship if that is the prima facie perception of the oncology specialty.
 

Dispelling myths and creating community via social media

A primary goal of consultation with a newly-diagnosed cancer patient is for the patient to feel that the oncologist will be there to take care of them, regardless of what the future holds.

Dr. Lewis has found that social media can potentially extend that feeling to a global community of patients, caregivers, and others seeking information relevant to a cancer diagnosis. He believes that oncologists have an opportunity to dispel myths and fears by being attentive to the real-life concerns of patients.

Dr. Lewis took advantage of this opportunity when he underwent a Whipple procedure (pancreaticoduodenectomy) for a pancreatic neuroendocrine tumor. He and the hospital’s media services staff “live-tweeted” his surgery and recovery.

With those tweets, Dr. Lewis demystified each step of a major surgical procedure. From messages he received on social media, Dr. Lewis knows he made the decision to have a Whipple procedure more acceptable to other patients.

His personal medical experience notwithstanding, Dr. Lewis acknowledged that every patient’s circumstances are unique.

Oncologists cannot possibly empathize with every circumstance. However, when they show sensitivity to personal elements of the cancer experience, they shed light on the complicated role they play in patient care and can facilitate good decision-making among patients across the globe.
 

Social media for professional development and patient care

The publication of his 2011 essay was gratifying for Dr. Lewis, but the finite number of comments he received thereafter illustrated the rather limited audience that traditional academic publications have and the laborious process for subsequent interaction (J Clin Oncol. 2011 Aug 1;29[22]:3103-4).

First as an observer and later as a participant on social media, Dr. Lewis appreciated that teaching points and publications can be amplified by global distribution and the potential for informal bidirectional communication.

Social media platforms enable physicians to connect with a larger audience through participative communication, in which users develop, share, and react to content (N Engl J Med. 2009 Aug 13;361[7]:649-51).

Dr. Lewis reflected on how oncologists are challenged to sort through the thousands of oncology-focused publications annually. Through social media, one can see the studies on which the experts are commenting and appreciate the nuances that contextualize the results. Focused interactions with renowned doctors, at regular intervals, require little formality.

Online journal clubs enable the sharing of ideas, opinions, multimedia resources, and references across institutional and international borders (J Gen Intern Med. 2014 Oct;29[10]:1317-8).
 

Social media in oncology: Accomplishments and promise

The development of broadband Internet, wireless connectivity, and social media for peer-to-peer and general communication are among the major technological advances that have transformed medical communication.

As an organization, COSMO aims to describe, understand, and improve the use of social media to increase the penetration of evidence-based guidelines and research insights into clinical practice (Future Oncol. 2017 Jun;13[15]:1281-5).

At the inaugural COSMO meeting, areas of progress since COSMO’s inception in 2015 were highlighted, including:

• The involvement of cancer professionals and advocates in multiple distinctive platforms.
• The development of hashtag libraries to aggregate interest groups and topics.
• The refinement of strategies for engaging advocates with attention to inclusiveness.
• A steady trajectory of growth in tweeting at scientific conferences.

An overarching theme of the COSMO meeting was “authenticity,” a virtue that is easy to admire but requires conscious, consistent effort to achieve.

Disclosure of conflicts of interest and avoiding using social media simply as a recruitment tool for clinical trials are basic components of accurate self-representation.

In addition, Dr. Lewis advocated for sharing personal experiences in a component of social media posts so oncologists can show humanity as a feature of their professional online identity and inherent nature.

Dr. Lewis disclosed consultancy with Medscape/WebMD, which are owned by the same parent company as MDedge. He also disclosed relationships with Foundation Medicine, Natera, Exelixis, QED, HalioDX, and Ipsen.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Sharing their personal experiences on social media can emphasize oncologists’ humanity and have substantive, beneficial effects on patient care, according to a presentation at the Collaboration for Outcomes using Social Media in Oncology (COSMO) inaugural meeting.

Mark A. Lewis, MD, explained to the COSMO meeting audience how storytelling on social media can educate and engage patients, advocates, and professional colleagues – advancing knowledge, dispelling misinformation, and promoting clinical research.

Dr. Lewis, an oncologist at Intermountain Healthcare in Salt Lake City, reflected on the bifid roles of oncologists as scientists engaged in life-long learning and humanists who can internalize and appreciate the unique character and circumstances of their patients.

Patients who have serious illnesses are necessarily aggregated by statistics. However, in an essay published in 2011, Dr. Lewis noted that “each individual patient partakes in a unique, irreproducible experiment where n = 1” (J Clin Oncol. 2011 Aug 1;29[22]:3103-4).

Dr. Lewis highlighted the duality of individual data points on a survival curve as descriptors of common disease trajectories and treatment effects. However, those data points also conceal important narratives regarding the most highly valued aspects of the doctor-patient relationship and the impact of cancer treatment on patients’ lives.

In referring to the futuristic essay “Ars Brevis,” Dr. Lewis contrasted the humanism of oncology specialists in the present day with the fictional image of data-regurgitating robots programmed to maximize the efficiency of each patient encounter (J Clin Oncol. 2013 May 10;31[14]:1792-4).

Dr. Lewis reminded attendees that to practice medicine without using both “head and heart” undermines the inherent nature of medical care.

Unfortunately, that perspective may not match the public perception of oncologists. Dr. Lewis described his experience of typing “oncologists are” into an Internet search engine and seeing the auto-complete function prompt words such as “criminals,” “evil,” “murderers,” and “confused.”

Obviously, it is hard to establish a trusting patient-doctor relationship if that is the prima facie perception of the oncology specialty.
 

Dispelling myths and creating community via social media

A primary goal of consultation with a newly-diagnosed cancer patient is for the patient to feel that the oncologist will be there to take care of them, regardless of what the future holds.

Dr. Lewis has found that social media can potentially extend that feeling to a global community of patients, caregivers, and others seeking information relevant to a cancer diagnosis. He believes that oncologists have an opportunity to dispel myths and fears by being attentive to the real-life concerns of patients.

Dr. Lewis took advantage of this opportunity when he underwent a Whipple procedure (pancreaticoduodenectomy) for a pancreatic neuroendocrine tumor. He and the hospital’s media services staff “live-tweeted” his surgery and recovery.

With those tweets, Dr. Lewis demystified each step of a major surgical procedure. From messages he received on social media, Dr. Lewis knows he made the decision to have a Whipple procedure more acceptable to other patients.

His personal medical experience notwithstanding, Dr. Lewis acknowledged that every patient’s circumstances are unique.

Oncologists cannot possibly empathize with every circumstance. However, when they show sensitivity to personal elements of the cancer experience, they shed light on the complicated role they play in patient care and can facilitate good decision-making among patients across the globe.
 

Social media for professional development and patient care

The publication of his 2011 essay was gratifying for Dr. Lewis, but the finite number of comments he received thereafter illustrated the rather limited audience that traditional academic publications have and the laborious process for subsequent interaction (J Clin Oncol. 2011 Aug 1;29[22]:3103-4).

First as an observer and later as a participant on social media, Dr. Lewis appreciated that teaching points and publications can be amplified by global distribution and the potential for informal bidirectional communication.

Social media platforms enable physicians to connect with a larger audience through participative communication, in which users develop, share, and react to content (N Engl J Med. 2009 Aug 13;361[7]:649-51).

Dr. Lewis reflected on how oncologists are challenged to sort through the thousands of oncology-focused publications annually. Through social media, one can see the studies on which the experts are commenting and appreciate the nuances that contextualize the results. Focused interactions with renowned doctors, at regular intervals, require little formality.

Online journal clubs enable the sharing of ideas, opinions, multimedia resources, and references across institutional and international borders (J Gen Intern Med. 2014 Oct;29[10]:1317-8).
 

Social media in oncology: Accomplishments and promise

The development of broadband Internet, wireless connectivity, and social media for peer-to-peer and general communication are among the major technological advances that have transformed medical communication.

As an organization, COSMO aims to describe, understand, and improve the use of social media to increase the penetration of evidence-based guidelines and research insights into clinical practice (Future Oncol. 2017 Jun;13[15]:1281-5).

At the inaugural COSMO meeting, areas of progress since COSMO’s inception in 2015 were highlighted, including:

• The involvement of cancer professionals and advocates in multiple distinctive platforms.
• The development of hashtag libraries to aggregate interest groups and topics.
• The refinement of strategies for engaging advocates with attention to inclusiveness.
• A steady trajectory of growth in tweeting at scientific conferences.

An overarching theme of the COSMO meeting was “authenticity,” a virtue that is easy to admire but requires conscious, consistent effort to achieve.

Disclosure of conflicts of interest and avoiding using social media simply as a recruitment tool for clinical trials are basic components of accurate self-representation.

In addition, Dr. Lewis advocated for sharing personal experiences in a component of social media posts so oncologists can show humanity as a feature of their professional online identity and inherent nature.

Dr. Lewis disclosed consultancy with Medscape/WebMD, which are owned by the same parent company as MDedge. He also disclosed relationships with Foundation Medicine, Natera, Exelixis, QED, HalioDX, and Ipsen.


Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.

Immunotherapy with checkpoint inhibitors has ushered in a new era of cancer therapy, with some patients showing dramatic responses and significantly better outcomes than with other therapies across many cancer types. But some patients do worse, sometimes much worse.

A subset of patients who undergo immunotherapy experience unexpected, rapid disease progression, with a dramatic acceleration of disease trajectory. They also have a shorter progression-free survival and overall survival than would have been expected.

This has been described as hyperprogression and has been termed “hyperprogressive disease” (HPD). It has been seen in a variety of cancers; the incidence ranges from 4% to 29% in the studies reported to date.

There has been some debate over whether this is a real phenomenon or whether it is part of the natural course of disease.

HPD is a “provocative phenomenon,” wrote the authors of a recent commentary entitled “Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?”

“This phenomenon has polarized oncologists who debate that this could still reflect the natural history of the disease,” said the author of another commentary.

But the tide is now turning toward acceptance of HPD, said Kartik Sehgal, MD, an oncologist at Dana-Farber Cancer Institute and Harvard University, both in Boston.

“With publication of multiple clinical reports of different cancer types worldwide, hyperprogression is now accepted by most oncologists to be a true phenomenon rather than natural progression of disease,” Dr. Sehgal said.

He authored an invited commentary in JAMA Network Openabout one of the latest meta-analyses (JAMA Netw Open. 2021;4[3]:e211136) to investigate HPD during immunotherapy. One of the biggest issues is that the studies that have reported on HPD have been retrospective, with a lack of comparator groups and a lack of a standardized definition of hyperprogression. Dr. Sehgal emphasized the need to study hyperprogression in well-designed prospective studies.
 

Existing data on HPD

HPD was described as “a new pattern of progression” seen in patients undergoing immune checkpoint inhibitor therapy in a 2017 article published in Clinical Cancer Research. Authors Stephane Champiat, MD, PhD, of Institut Gustave Roussy, Universite Paris Saclay, Villejuif, France, and colleagues cited “anecdotal occurrences” of HPD among patients in phase 1 trials of anti–PD-1/PD-L1 agents.

In that study, HPD was defined by tumor growth rate ratio. The incidence was 9% among 213 patients.

The findings raised concerns about treating elderly patients with anti–PD-1/PD-L1 monotherapy, according to the authors, who called for further study.

That same year, Roberto Ferrara, MD, and colleagues from the Insitut Gustave Roussy reported additional data indicating an incidence of HPD of 16% among 333 patients with non–small cell lung cancer who underwent immunotherapy at eight centers from 2012 to 2017. The findings, which were presented at the 2017 World Conference on Lung Cancer and reported at the time by this news organization, also showed that the incidence of HPD was higher with immunotherapy than with single-agent chemotherapy (5%).

Median overall survival (OS) was just 3.4 months among those with HPD, compared with 13 months in the overall study population – worse, even, than the median 5.4-month OS observed among patients with progressive disease who received immunotherapy.

In the wake of these findings, numerous researchers have attempted to better define HPD, its incidence, and patient factors associated with developing HPD while undergoing immunotherapy.

However, there is little so far to show for those efforts, Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in an interview.

“Many questions remain to be answered,” said Dr. Subbiah, clinical medical director of the Clinical Center for Targeted Therapy in the division of cancer medicine at MD Anderson. He was the senior author of the “Fact, Fiction, or Alternative Fact?” commentary.

Work is underway to elucidate biological mechanisms. Some groups have implicated the Fc region of antibodies. Another group has reported EGFR and MDM2/MDM4 amplifications in patients with HPD, Dr. Subbiah and colleagues noted.

Other “proposed contributing pathological mechanisms include modulation of tumor immune microenvironment through macrophages and regulatory T cells as well as activation of oncogenic signaling pathways,” noted Dr. Sehgal.

Both groups of authors emphasize the urgent need for prospective studies.

It is imperative to confirm underlying biology, predict which patients are at risk, and identify therapeutic directions for patients who experience HPD, Dr. Subbiah said.

The main challenge is defining HPD, he added. Definitions that have been proposed include tumor growth at least two times greater than in control persons, a 15% increase in tumor burden in a set period, and disease progression of 50% from the first evaluation before treatment, he said.

The recent meta-analysis by Hyo Jung Park, MD, PhD, and colleagues, which Dr. Sehgal addressed in his invited commentary, highlights the many approaches used for defining HPD.

Depending on the definition used, the incidence of HPD across 24 studies involving more than 3,100 patients ranged from 5.9% to 43.1%.

“Hyperprogressive disease could be overestimated or underestimated based on current assessment,” Dr. Park and colleagues concluded. They highlighted the importance of “establishing uniform and clinically relevant criteria based on currently available evidence.”
 

Steps for solving the HPD mystery

“I think we need to come up with consensus criteria for an HPD definition. We need a unified definition,” Dr. Subbiah said. “We also need to design prospective studies to prove or disprove the immunotherapy-HPD association.”

Prospective registries with independent review of patients with suspected immunotherapy-related HPD would be useful for assessing the true incidence and the biology of HPD among patients undergoing immunotherapy, he suggested.

“We need to know the immunologic signals of HPD. This can give us an idea if patients can be prospectively identified for being at risk,” he said. “We also need to know what to do if they are at risk.”

Dr. Sehgal also called for consensus on an HPD definition, with input from a multidisciplinary group that includes “colleagues from radiology, medical oncology, radiation oncology. Getting expertise from different disciplines would be helpful,” he said.

Dr. Park and colleagues suggested several key requirements for an optimal HP definition, such as the inclusion of multiple variables for measuring tumor growth acceleration, “sufficiently quantitative” criteria for determining time to failure, and establishment of a standardized measure of tumor growth acceleration.

The agreed-upon definition of HPD could be applied to patients in a prospective registry and to existing trial data, Dr. Sehgal said.

“Eventually, the goal of this exercise is to [determine] how we can help our patients the best, having a biomarker that can at least inform us in terms of being aware and being proactive in terms of looking for this ... so that interventions can be brought on earlier,” he said.

“If we know what may be a biological mechanism, we can design trials that are designed to look at how to overcome that HPD,” he said.

Dr. Sehgal said he believes HPD is triggered in some way by treatment, including immunotherapy, chemotherapy, and targeted therapy, but perhaps in different ways for each.

He estimated the true incidence of immunotherapy-related HPD will be in the 9%-10% range.

“This is a substantial number of patients, so it’s important that we try to understand this phenomenon, using, again, uniform criteria,” he said.
 

Current treatment decision-making

Until more is known, Dr. Sehgal said he considers the potential risk factors when treating patients with immunotherapy.

For example, the presence of MDM2 or MDM4 amplification on a genomic profile may factor into his treatment decision-making when it comes to using immunotherapy or immunotherapy in combination with chemotherapy, he said.

“Is that the only factor that is going to make me choose one thing or another? No,” Dr. Sehgal said. However, he said it would make him more “proactive in making sure the patient is doing clinically okay” and in determining when to obtain on-treatment imaging studies.

Dr. Subbiah emphasized the relative benefit of immunotherapy, noting that survival with chemotherapy for many difficult-to-treat cancers in the relapsed/refractory metastatic setting is less than 2 years.

Immunotherapy with checkpoint inhibitors has allowed some of these patients to live longer (with survival reported to be more than 10 years for patients with metastatic melanoma).

“Immunotherapy has been a game changer; it has been transformative in the lives of these patients,” Dr. Subbiah said. “So unless there is any other contraindication, the benefit of receiving immunotherapy for an approved indication far outweighs the risk of HPD.”

A version of this article first appeared on Medscape.com.

Immunotherapy with checkpoint inhibitors has ushered in a new era of cancer therapy, with some patients showing dramatic responses and significantly better outcomes than with other therapies across many cancer types. But some patients do worse, sometimes much worse.

A subset of patients who undergo immunotherapy experience unexpected, rapid disease progression, with a dramatic acceleration of disease trajectory. They also have a shorter progression-free survival and overall survival than would have been expected.

This has been described as hyperprogression and has been termed “hyperprogressive disease” (HPD). It has been seen in a variety of cancers; the incidence ranges from 4% to 29% in the studies reported to date.

There has been some debate over whether this is a real phenomenon or whether it is part of the natural course of disease.

HPD is a “provocative phenomenon,” wrote the authors of a recent commentary entitled “Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?”

“This phenomenon has polarized oncologists who debate that this could still reflect the natural history of the disease,” said the author of another commentary.

But the tide is now turning toward acceptance of HPD, said Kartik Sehgal, MD, an oncologist at Dana-Farber Cancer Institute and Harvard University, both in Boston.

“With publication of multiple clinical reports of different cancer types worldwide, hyperprogression is now accepted by most oncologists to be a true phenomenon rather than natural progression of disease,” Dr. Sehgal said.

He authored an invited commentary in JAMA Network Openabout one of the latest meta-analyses (JAMA Netw Open. 2021;4[3]:e211136) to investigate HPD during immunotherapy. One of the biggest issues is that the studies that have reported on HPD have been retrospective, with a lack of comparator groups and a lack of a standardized definition of hyperprogression. Dr. Sehgal emphasized the need to study hyperprogression in well-designed prospective studies.
 

Existing data on HPD

HPD was described as “a new pattern of progression” seen in patients undergoing immune checkpoint inhibitor therapy in a 2017 article published in Clinical Cancer Research. Authors Stephane Champiat, MD, PhD, of Institut Gustave Roussy, Universite Paris Saclay, Villejuif, France, and colleagues cited “anecdotal occurrences” of HPD among patients in phase 1 trials of anti–PD-1/PD-L1 agents.

In that study, HPD was defined by tumor growth rate ratio. The incidence was 9% among 213 patients.

The findings raised concerns about treating elderly patients with anti–PD-1/PD-L1 monotherapy, according to the authors, who called for further study.

That same year, Roberto Ferrara, MD, and colleagues from the Insitut Gustave Roussy reported additional data indicating an incidence of HPD of 16% among 333 patients with non–small cell lung cancer who underwent immunotherapy at eight centers from 2012 to 2017. The findings, which were presented at the 2017 World Conference on Lung Cancer and reported at the time by this news organization, also showed that the incidence of HPD was higher with immunotherapy than with single-agent chemotherapy (5%).

Median overall survival (OS) was just 3.4 months among those with HPD, compared with 13 months in the overall study population – worse, even, than the median 5.4-month OS observed among patients with progressive disease who received immunotherapy.

In the wake of these findings, numerous researchers have attempted to better define HPD, its incidence, and patient factors associated with developing HPD while undergoing immunotherapy.

However, there is little so far to show for those efforts, Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in an interview.

“Many questions remain to be answered,” said Dr. Subbiah, clinical medical director of the Clinical Center for Targeted Therapy in the division of cancer medicine at MD Anderson. He was the senior author of the “Fact, Fiction, or Alternative Fact?” commentary.

Work is underway to elucidate biological mechanisms. Some groups have implicated the Fc region of antibodies. Another group has reported EGFR and MDM2/MDM4 amplifications in patients with HPD, Dr. Subbiah and colleagues noted.

Other “proposed contributing pathological mechanisms include modulation of tumor immune microenvironment through macrophages and regulatory T cells as well as activation of oncogenic signaling pathways,” noted Dr. Sehgal.

Both groups of authors emphasize the urgent need for prospective studies.

It is imperative to confirm underlying biology, predict which patients are at risk, and identify therapeutic directions for patients who experience HPD, Dr. Subbiah said.

The main challenge is defining HPD, he added. Definitions that have been proposed include tumor growth at least two times greater than in control persons, a 15% increase in tumor burden in a set period, and disease progression of 50% from the first evaluation before treatment, he said.

The recent meta-analysis by Hyo Jung Park, MD, PhD, and colleagues, which Dr. Sehgal addressed in his invited commentary, highlights the many approaches used for defining HPD.

Depending on the definition used, the incidence of HPD across 24 studies involving more than 3,100 patients ranged from 5.9% to 43.1%.

“Hyperprogressive disease could be overestimated or underestimated based on current assessment,” Dr. Park and colleagues concluded. They highlighted the importance of “establishing uniform and clinically relevant criteria based on currently available evidence.”
 

Steps for solving the HPD mystery

“I think we need to come up with consensus criteria for an HPD definition. We need a unified definition,” Dr. Subbiah said. “We also need to design prospective studies to prove or disprove the immunotherapy-HPD association.”

Prospective registries with independent review of patients with suspected immunotherapy-related HPD would be useful for assessing the true incidence and the biology of HPD among patients undergoing immunotherapy, he suggested.

“We need to know the immunologic signals of HPD. This can give us an idea if patients can be prospectively identified for being at risk,” he said. “We also need to know what to do if they are at risk.”

Dr. Sehgal also called for consensus on an HPD definition, with input from a multidisciplinary group that includes “colleagues from radiology, medical oncology, radiation oncology. Getting expertise from different disciplines would be helpful,” he said.

Dr. Park and colleagues suggested several key requirements for an optimal HP definition, such as the inclusion of multiple variables for measuring tumor growth acceleration, “sufficiently quantitative” criteria for determining time to failure, and establishment of a standardized measure of tumor growth acceleration.

The agreed-upon definition of HPD could be applied to patients in a prospective registry and to existing trial data, Dr. Sehgal said.

“Eventually, the goal of this exercise is to [determine] how we can help our patients the best, having a biomarker that can at least inform us in terms of being aware and being proactive in terms of looking for this ... so that interventions can be brought on earlier,” he said.

“If we know what may be a biological mechanism, we can design trials that are designed to look at how to overcome that HPD,” he said.

Dr. Sehgal said he believes HPD is triggered in some way by treatment, including immunotherapy, chemotherapy, and targeted therapy, but perhaps in different ways for each.

He estimated the true incidence of immunotherapy-related HPD will be in the 9%-10% range.

“This is a substantial number of patients, so it’s important that we try to understand this phenomenon, using, again, uniform criteria,” he said.
 

Current treatment decision-making

Until more is known, Dr. Sehgal said he considers the potential risk factors when treating patients with immunotherapy.

For example, the presence of MDM2 or MDM4 amplification on a genomic profile may factor into his treatment decision-making when it comes to using immunotherapy or immunotherapy in combination with chemotherapy, he said.

“Is that the only factor that is going to make me choose one thing or another? No,” Dr. Sehgal said. However, he said it would make him more “proactive in making sure the patient is doing clinically okay” and in determining when to obtain on-treatment imaging studies.

Dr. Subbiah emphasized the relative benefit of immunotherapy, noting that survival with chemotherapy for many difficult-to-treat cancers in the relapsed/refractory metastatic setting is less than 2 years.

Immunotherapy with checkpoint inhibitors has allowed some of these patients to live longer (with survival reported to be more than 10 years for patients with metastatic melanoma).

“Immunotherapy has been a game changer; it has been transformative in the lives of these patients,” Dr. Subbiah said. “So unless there is any other contraindication, the benefit of receiving immunotherapy for an approved indication far outweighs the risk of HPD.”

A version of this article first appeared on Medscape.com.

Immunotherapy with checkpoint inhibitors has ushered in a new era of cancer therapy, with some patients showing dramatic responses and significantly better outcomes than with other therapies across many cancer types. But some patients do worse, sometimes much worse.

A subset of patients who undergo immunotherapy experience unexpected, rapid disease progression, with a dramatic acceleration of disease trajectory. They also have a shorter progression-free survival and overall survival than would have been expected.

This has been described as hyperprogression and has been termed “hyperprogressive disease” (HPD). It has been seen in a variety of cancers; the incidence ranges from 4% to 29% in the studies reported to date.

There has been some debate over whether this is a real phenomenon or whether it is part of the natural course of disease.

HPD is a “provocative phenomenon,” wrote the authors of a recent commentary entitled “Hyperprogression and Immunotherapy: Fact, Fiction, or Alternative Fact?”

“This phenomenon has polarized oncologists who debate that this could still reflect the natural history of the disease,” said the author of another commentary.

But the tide is now turning toward acceptance of HPD, said Kartik Sehgal, MD, an oncologist at Dana-Farber Cancer Institute and Harvard University, both in Boston.

“With publication of multiple clinical reports of different cancer types worldwide, hyperprogression is now accepted by most oncologists to be a true phenomenon rather than natural progression of disease,” Dr. Sehgal said.

He authored an invited commentary in JAMA Network Openabout one of the latest meta-analyses (JAMA Netw Open. 2021;4[3]:e211136) to investigate HPD during immunotherapy. One of the biggest issues is that the studies that have reported on HPD have been retrospective, with a lack of comparator groups and a lack of a standardized definition of hyperprogression. Dr. Sehgal emphasized the need to study hyperprogression in well-designed prospective studies.
 

Existing data on HPD

HPD was described as “a new pattern of progression” seen in patients undergoing immune checkpoint inhibitor therapy in a 2017 article published in Clinical Cancer Research. Authors Stephane Champiat, MD, PhD, of Institut Gustave Roussy, Universite Paris Saclay, Villejuif, France, and colleagues cited “anecdotal occurrences” of HPD among patients in phase 1 trials of anti–PD-1/PD-L1 agents.

In that study, HPD was defined by tumor growth rate ratio. The incidence was 9% among 213 patients.

The findings raised concerns about treating elderly patients with anti–PD-1/PD-L1 monotherapy, according to the authors, who called for further study.

That same year, Roberto Ferrara, MD, and colleagues from the Insitut Gustave Roussy reported additional data indicating an incidence of HPD of 16% among 333 patients with non–small cell lung cancer who underwent immunotherapy at eight centers from 2012 to 2017. The findings, which were presented at the 2017 World Conference on Lung Cancer and reported at the time by this news organization, also showed that the incidence of HPD was higher with immunotherapy than with single-agent chemotherapy (5%).

Median overall survival (OS) was just 3.4 months among those with HPD, compared with 13 months in the overall study population – worse, even, than the median 5.4-month OS observed among patients with progressive disease who received immunotherapy.

In the wake of these findings, numerous researchers have attempted to better define HPD, its incidence, and patient factors associated with developing HPD while undergoing immunotherapy.

However, there is little so far to show for those efforts, Vivek Subbiah, MD, of the University of Texas MD Anderson Cancer Center, Houston, said in an interview.

“Many questions remain to be answered,” said Dr. Subbiah, clinical medical director of the Clinical Center for Targeted Therapy in the division of cancer medicine at MD Anderson. He was the senior author of the “Fact, Fiction, or Alternative Fact?” commentary.

Work is underway to elucidate biological mechanisms. Some groups have implicated the Fc region of antibodies. Another group has reported EGFR and MDM2/MDM4 amplifications in patients with HPD, Dr. Subbiah and colleagues noted.

Other “proposed contributing pathological mechanisms include modulation of tumor immune microenvironment through macrophages and regulatory T cells as well as activation of oncogenic signaling pathways,” noted Dr. Sehgal.

Both groups of authors emphasize the urgent need for prospective studies.

It is imperative to confirm underlying biology, predict which patients are at risk, and identify therapeutic directions for patients who experience HPD, Dr. Subbiah said.

The main challenge is defining HPD, he added. Definitions that have been proposed include tumor growth at least two times greater than in control persons, a 15% increase in tumor burden in a set period, and disease progression of 50% from the first evaluation before treatment, he said.

The recent meta-analysis by Hyo Jung Park, MD, PhD, and colleagues, which Dr. Sehgal addressed in his invited commentary, highlights the many approaches used for defining HPD.

Depending on the definition used, the incidence of HPD across 24 studies involving more than 3,100 patients ranged from 5.9% to 43.1%.

“Hyperprogressive disease could be overestimated or underestimated based on current assessment,” Dr. Park and colleagues concluded. They highlighted the importance of “establishing uniform and clinically relevant criteria based on currently available evidence.”
 

Steps for solving the HPD mystery

“I think we need to come up with consensus criteria for an HPD definition. We need a unified definition,” Dr. Subbiah said. “We also need to design prospective studies to prove or disprove the immunotherapy-HPD association.”

Prospective registries with independent review of patients with suspected immunotherapy-related HPD would be useful for assessing the true incidence and the biology of HPD among patients undergoing immunotherapy, he suggested.

“We need to know the immunologic signals of HPD. This can give us an idea if patients can be prospectively identified for being at risk,” he said. “We also need to know what to do if they are at risk.”

Dr. Sehgal also called for consensus on an HPD definition, with input from a multidisciplinary group that includes “colleagues from radiology, medical oncology, radiation oncology. Getting expertise from different disciplines would be helpful,” he said.

Dr. Park and colleagues suggested several key requirements for an optimal HP definition, such as the inclusion of multiple variables for measuring tumor growth acceleration, “sufficiently quantitative” criteria for determining time to failure, and establishment of a standardized measure of tumor growth acceleration.

The agreed-upon definition of HPD could be applied to patients in a prospective registry and to existing trial data, Dr. Sehgal said.

“Eventually, the goal of this exercise is to [determine] how we can help our patients the best, having a biomarker that can at least inform us in terms of being aware and being proactive in terms of looking for this ... so that interventions can be brought on earlier,” he said.

“If we know what may be a biological mechanism, we can design trials that are designed to look at how to overcome that HPD,” he said.

Dr. Sehgal said he believes HPD is triggered in some way by treatment, including immunotherapy, chemotherapy, and targeted therapy, but perhaps in different ways for each.

He estimated the true incidence of immunotherapy-related HPD will be in the 9%-10% range.

“This is a substantial number of patients, so it’s important that we try to understand this phenomenon, using, again, uniform criteria,” he said.
 

Current treatment decision-making

Until more is known, Dr. Sehgal said he considers the potential risk factors when treating patients with immunotherapy.

For example, the presence of MDM2 or MDM4 amplification on a genomic profile may factor into his treatment decision-making when it comes to using immunotherapy or immunotherapy in combination with chemotherapy, he said.

“Is that the only factor that is going to make me choose one thing or another? No,” Dr. Sehgal said. However, he said it would make him more “proactive in making sure the patient is doing clinically okay” and in determining when to obtain on-treatment imaging studies.

Dr. Subbiah emphasized the relative benefit of immunotherapy, noting that survival with chemotherapy for many difficult-to-treat cancers in the relapsed/refractory metastatic setting is less than 2 years.

Immunotherapy with checkpoint inhibitors has allowed some of these patients to live longer (with survival reported to be more than 10 years for patients with metastatic melanoma).

“Immunotherapy has been a game changer; it has been transformative in the lives of these patients,” Dr. Subbiah said. “So unless there is any other contraindication, the benefit of receiving immunotherapy for an approved indication far outweighs the risk of HPD.”

A version of this article first appeared on Medscape.com.

Federal advisers have supported the efforts of pharmaceutical companies in four of six cases in which these firms are fighting to maintain cancer indications for approved drugs. The advisers voted against the companies in two cases.

The staff of the Food and Drug Administration will now consider these votes as they decide what to do regarding the six cases of what they have termed “dangling” accelerated approvals.

“One of the reasons I think we’re convening today is to prevent these accelerated approvals from dangling ad infinitum,” commented one of the members of the advisory panel.

In these cases, companies have been unable to prove the expected benefits that led the FDA to grant accelerated approvals for these indications.

These accelerated approvals, which are often based on surrogate endpoints, such as overall response rates, are granted on the condition that further findings show a clinical benefit – such as in progression-free survival or overall survival – in larger trials.

The FDA tasked its Oncologic Drugs Advisory Committee (ODAC) with conducting the review of the six accelerated approvals for cancer indications at a 3-day meeting (April 27-29).

These reviews were only for specific cancer indications and will not lead to the removal of drugs from the market. These drugs have already been approved for several cancer indications. For example, one of the drugs that was reviewed, pembrolizumab (Keytruda), is approved in the United States for 28 indications.

The FDA is facing growing pains in its efforts to manage the rapidly changing landscape for these immune checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials, owing in part to the agency’s willingness to accept surrogate markers for accelerated approvals. Although some companies have struggled with these, others have built strong cases for the use of their checkpoint inhibitors for these indications.

The ODAC panelists, for example, noted the emergence of nivolumab (Opdivo) as an option for patients with gastric cancer as a reason for seeking to withdraw an indication for pembrolizumab (Keytruda) for this disease.

Just weeks before the meeting, on April 16, the FDA approved nivolumab plus chemotherapy as a first-line treatment for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. This was a full approval based on data showing an overall survival benefit from a phase 3 trial.
 

Votes by indication

On April 29, the last day of the meeting, the ODAC panel voted 6-2 against maintaining pembrolizumab’s indication as monotherapy for an advanced form of gastric cancer. This was an accelerated approval (granted in 2017) that was based on overall response rates from an open-label trial.

That last day of the meeting also saw another negative vote. On April 29, the ODAC panel voted 5-4 against maintaining an indication for nivolumab in patients with hepatocellular carcinoma (HCC) who were previously treated with sorafenib (Nexavar).

This accelerated approval for nivolumab was granted in 2017. The FDA said it had requested ODAC’s feedback on this indication because of the recent full approval of another checkpoint inhibitor for HCC, atezolizumab (Tecentriq), in combination with bevacizumab (Avastin) for patients with unresectable or metastatic diseases who have not received prior systemic therapy. This full approval (in May 2020) was based on an overall survival benefit.

There was one last vote on the third day of the meeting, and it was positive. The ODAC panel voted 8-0 in favor of maintaining the indication for the use of pembrolizumab as monotherapy for patients with HCC who have previously been treated with sorafenib.

The FDA altered the composition of the ODAC panel during the week, adding members in some cases who had expertise in particular cancers. That led to different totals for the week’s ODAC votes, as shown in the tallies summarized below.

On the first day of the meeting (April 27), the ODAC panel voted 7-2 in favor of maintaining a breast cancer indication for atezolizumab (Tecentriq). This covered use of the immunotherapy in combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1.

The second day of the meeting (April 28) also saw two positive votes. The ODAC panel voted 10-1 for maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial. The panel also voted 5-3 for maintaining the indication for pembrolizumab in patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1.

The FDA is not bound to follow the voting and recommendations of its advisory panels, but it usually does so.
 

Managing shifts in treatment

In both of the cases in which ODAC voted against maintaining indications, Richard Pazdur, MD, the FDA’s top regulator for cancer medicines, jumped into the debate. Dr. Pazdur countered arguments put forward by representatives of the manufacturers as they sought to maintain indications for their drugs.

Merck officials and representatives argued for pembrolizumab, saying that maintaining the gastric cancer indication might help patients whose disease has progressed despite earlier treatment.

Dr. Pazdur emphasized that the agency would help Merck and physicians to have access to pembrolizumab for these patients even if this one indication were to be withdrawn. But Dr. Pazdur and ODAC members also noted the recent shift in the landscape for gastric cancer, with the recent approval of a new indication for nivolumab.

“I want to emphasize to the patient community out there [that] we firmly believe in the role of checkpoint inhibitors in this disease,” Dr. Pazdur said during the discussion of the indication for pembrolizumab for gastric cancer. “We have to be cognizant of what is the appropriate setting for that, and it currently is in the first line.”

Dr. Pazdur noted that two studies had failed to confirm the expected benefit from pembrolizumab for patients with more advanced disease. Still, if “small numbers” of patients with advanced disease wanted access to Merck’s drug, the FDA and the company could accommodate them. The FDA could delay the removal of the gastric indication to allow patients to continue receiving it. The FDA also could work with physicians on other routes to provide the medicine, such as through single-patient investigational new drug applications or an expanded access program.

“Or Merck can alternatively give the drug gratis to patients,” Dr. Pazdur said.
 

#ProjectFacilitate for expanded access

One of Merck’s speakers at the ODAC meeting, Peter Enzinger, MD, of the Dana-Farber Cancer Institute, Boston, objected to Dr. Pazdur’s plan.

A loss of the gastric indication for pembrolizumab would result in patients with advanced cancer missing out on a chance to try this therapy. Some patients will not have had a chance to try a checkpoint inhibitor earlier in their treatment, and a loss of the indication would cost them that opportunity, he said.

“An expanded-access program sounds very nice, but the reality is that our patients are incredibly sick and that weeks matter,” Dr. Enzinger said, citing administrative hurdles as a barrier to treatment.

“Our patients just don’t have the time for that, and therefore I don’t think an expanded access program is the way to go,” Dr. Enzinger said.

Dr. Pazdur responded to these objections by highlighting an initiative called Project Facilitate at the FDA’s Oncology Center for Excellence. During the meeting, Dr. Pazdur’s division used its @FDAOncology Twitter handle to draw attention to this project.

ODAC panelist Diane Reidy-Lagunes, MD, of Memorial Sloan Kettering Cancer Center, New York, said she had struggled with this vote. She was one of the two panelists to vote in favor of keeping the indication.

“This is also incredibly hard for me. I actually changed it at the last minute,” she said of her vote.

But Dr. Reidy-Lagunes said she was concerned that some patients with advanced disease might not be able to get a checkpoint inhibitor.

“With disparities in healthcare and differences in the way that patients are treated throughout our country, I was nervous that they may not be able to get treated,” she said, noting that she shared her fellow panelists’ doubts about use of pembrolizumab as third-line treatment, owing to negative results in trials.

ODAC member David Mitchell, who served as a consumer representative, also said he found the vote on the gastric indication for pembrolizumab to be a difficult decision.

“As a patient with incurable cancer who’s now being given all three major classes of drugs to treat my disease in combination, these issues really cut close to home,” Mr. Mitchell said.

He said the expectation that the FDA’s expanded access program could help patients with advanced disease try pembrolizumab helped him decide to vote with the 6-2 majority against maintaining this gastric cancer approval.

His vote was based on “the changing treatment landscape.” There is general agreement that the patients in question should receive checkpoint inhibitors as first-line treatment, not third-line treatment, Mr. Mitchell said. The FDA should delay a withdrawal of the approval for pembrolizumab in this case and should allow a transition for those who missed out on treatment with a checkpoint inhibitor earlier in the disease course, he suggested.

“To protect the safety and well-being of patients, we have to base decisions on data,” Mr. Mitchell said. “The data don’t support maintaining the indication” for pembrolizumab.

 

Close split on nivolumab

In contrast to the 6-2 vote against maintaining the pembrolizumab indication, the ODAC panel split more closely, 5-4, on the question of maintaining an indication for the use as monotherapy of nivolumab in HCC.

ODAC panelist Philip C. Hoffman, MD, of the University of Chicago was among those who supported keeping the indication.

“There’s still an unmet need for second-line immunotherapy because there will always be some patients who are poor candidates for bevacizumab or who are not tolerating or responding to sorafenib,” he said.

ODAC panelist Mark A. Lewis, MD, of Intermountain Healthcare, Salt Lake City, said he voted “no” in part because he doubted that Bristol-Myers Squibb would be able to soon produce data for nivolumab that was needed to support this indication.

A version of this article first appeared on Medscape.com.

Federal advisers have supported the efforts of pharmaceutical companies in four of six cases in which these firms are fighting to maintain cancer indications for approved drugs. The advisers voted against the companies in two cases.

The staff of the Food and Drug Administration will now consider these votes as they decide what to do regarding the six cases of what they have termed “dangling” accelerated approvals.

“One of the reasons I think we’re convening today is to prevent these accelerated approvals from dangling ad infinitum,” commented one of the members of the advisory panel.

In these cases, companies have been unable to prove the expected benefits that led the FDA to grant accelerated approvals for these indications.

These accelerated approvals, which are often based on surrogate endpoints, such as overall response rates, are granted on the condition that further findings show a clinical benefit – such as in progression-free survival or overall survival – in larger trials.

The FDA tasked its Oncologic Drugs Advisory Committee (ODAC) with conducting the review of the six accelerated approvals for cancer indications at a 3-day meeting (April 27-29).

These reviews were only for specific cancer indications and will not lead to the removal of drugs from the market. These drugs have already been approved for several cancer indications. For example, one of the drugs that was reviewed, pembrolizumab (Keytruda), is approved in the United States for 28 indications.

The FDA is facing growing pains in its efforts to manage the rapidly changing landscape for these immune checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials, owing in part to the agency’s willingness to accept surrogate markers for accelerated approvals. Although some companies have struggled with these, others have built strong cases for the use of their checkpoint inhibitors for these indications.

The ODAC panelists, for example, noted the emergence of nivolumab (Opdivo) as an option for patients with gastric cancer as a reason for seeking to withdraw an indication for pembrolizumab (Keytruda) for this disease.

Just weeks before the meeting, on April 16, the FDA approved nivolumab plus chemotherapy as a first-line treatment for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. This was a full approval based on data showing an overall survival benefit from a phase 3 trial.
 

Votes by indication

On April 29, the last day of the meeting, the ODAC panel voted 6-2 against maintaining pembrolizumab’s indication as monotherapy for an advanced form of gastric cancer. This was an accelerated approval (granted in 2017) that was based on overall response rates from an open-label trial.

That last day of the meeting also saw another negative vote. On April 29, the ODAC panel voted 5-4 against maintaining an indication for nivolumab in patients with hepatocellular carcinoma (HCC) who were previously treated with sorafenib (Nexavar).

This accelerated approval for nivolumab was granted in 2017. The FDA said it had requested ODAC’s feedback on this indication because of the recent full approval of another checkpoint inhibitor for HCC, atezolizumab (Tecentriq), in combination with bevacizumab (Avastin) for patients with unresectable or metastatic diseases who have not received prior systemic therapy. This full approval (in May 2020) was based on an overall survival benefit.

There was one last vote on the third day of the meeting, and it was positive. The ODAC panel voted 8-0 in favor of maintaining the indication for the use of pembrolizumab as monotherapy for patients with HCC who have previously been treated with sorafenib.

The FDA altered the composition of the ODAC panel during the week, adding members in some cases who had expertise in particular cancers. That led to different totals for the week’s ODAC votes, as shown in the tallies summarized below.

On the first day of the meeting (April 27), the ODAC panel voted 7-2 in favor of maintaining a breast cancer indication for atezolizumab (Tecentriq). This covered use of the immunotherapy in combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1.

The second day of the meeting (April 28) also saw two positive votes. The ODAC panel voted 10-1 for maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial. The panel also voted 5-3 for maintaining the indication for pembrolizumab in patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1.

The FDA is not bound to follow the voting and recommendations of its advisory panels, but it usually does so.
 

Managing shifts in treatment

In both of the cases in which ODAC voted against maintaining indications, Richard Pazdur, MD, the FDA’s top regulator for cancer medicines, jumped into the debate. Dr. Pazdur countered arguments put forward by representatives of the manufacturers as they sought to maintain indications for their drugs.

Merck officials and representatives argued for pembrolizumab, saying that maintaining the gastric cancer indication might help patients whose disease has progressed despite earlier treatment.

Dr. Pazdur emphasized that the agency would help Merck and physicians to have access to pembrolizumab for these patients even if this one indication were to be withdrawn. But Dr. Pazdur and ODAC members also noted the recent shift in the landscape for gastric cancer, with the recent approval of a new indication for nivolumab.

“I want to emphasize to the patient community out there [that] we firmly believe in the role of checkpoint inhibitors in this disease,” Dr. Pazdur said during the discussion of the indication for pembrolizumab for gastric cancer. “We have to be cognizant of what is the appropriate setting for that, and it currently is in the first line.”

Dr. Pazdur noted that two studies had failed to confirm the expected benefit from pembrolizumab for patients with more advanced disease. Still, if “small numbers” of patients with advanced disease wanted access to Merck’s drug, the FDA and the company could accommodate them. The FDA could delay the removal of the gastric indication to allow patients to continue receiving it. The FDA also could work with physicians on other routes to provide the medicine, such as through single-patient investigational new drug applications or an expanded access program.

“Or Merck can alternatively give the drug gratis to patients,” Dr. Pazdur said.
 

#ProjectFacilitate for expanded access

One of Merck’s speakers at the ODAC meeting, Peter Enzinger, MD, of the Dana-Farber Cancer Institute, Boston, objected to Dr. Pazdur’s plan.

A loss of the gastric indication for pembrolizumab would result in patients with advanced cancer missing out on a chance to try this therapy. Some patients will not have had a chance to try a checkpoint inhibitor earlier in their treatment, and a loss of the indication would cost them that opportunity, he said.

“An expanded-access program sounds very nice, but the reality is that our patients are incredibly sick and that weeks matter,” Dr. Enzinger said, citing administrative hurdles as a barrier to treatment.

“Our patients just don’t have the time for that, and therefore I don’t think an expanded access program is the way to go,” Dr. Enzinger said.

Dr. Pazdur responded to these objections by highlighting an initiative called Project Facilitate at the FDA’s Oncology Center for Excellence. During the meeting, Dr. Pazdur’s division used its @FDAOncology Twitter handle to draw attention to this project.

ODAC panelist Diane Reidy-Lagunes, MD, of Memorial Sloan Kettering Cancer Center, New York, said she had struggled with this vote. She was one of the two panelists to vote in favor of keeping the indication.

“This is also incredibly hard for me. I actually changed it at the last minute,” she said of her vote.

But Dr. Reidy-Lagunes said she was concerned that some patients with advanced disease might not be able to get a checkpoint inhibitor.

“With disparities in healthcare and differences in the way that patients are treated throughout our country, I was nervous that they may not be able to get treated,” she said, noting that she shared her fellow panelists’ doubts about use of pembrolizumab as third-line treatment, owing to negative results in trials.

ODAC member David Mitchell, who served as a consumer representative, also said he found the vote on the gastric indication for pembrolizumab to be a difficult decision.

“As a patient with incurable cancer who’s now being given all three major classes of drugs to treat my disease in combination, these issues really cut close to home,” Mr. Mitchell said.

He said the expectation that the FDA’s expanded access program could help patients with advanced disease try pembrolizumab helped him decide to vote with the 6-2 majority against maintaining this gastric cancer approval.

His vote was based on “the changing treatment landscape.” There is general agreement that the patients in question should receive checkpoint inhibitors as first-line treatment, not third-line treatment, Mr. Mitchell said. The FDA should delay a withdrawal of the approval for pembrolizumab in this case and should allow a transition for those who missed out on treatment with a checkpoint inhibitor earlier in the disease course, he suggested.

“To protect the safety and well-being of patients, we have to base decisions on data,” Mr. Mitchell said. “The data don’t support maintaining the indication” for pembrolizumab.

 

Close split on nivolumab

In contrast to the 6-2 vote against maintaining the pembrolizumab indication, the ODAC panel split more closely, 5-4, on the question of maintaining an indication for the use as monotherapy of nivolumab in HCC.

ODAC panelist Philip C. Hoffman, MD, of the University of Chicago was among those who supported keeping the indication.

“There’s still an unmet need for second-line immunotherapy because there will always be some patients who are poor candidates for bevacizumab or who are not tolerating or responding to sorafenib,” he said.

ODAC panelist Mark A. Lewis, MD, of Intermountain Healthcare, Salt Lake City, said he voted “no” in part because he doubted that Bristol-Myers Squibb would be able to soon produce data for nivolumab that was needed to support this indication.

A version of this article first appeared on Medscape.com.

Federal advisers have supported the efforts of pharmaceutical companies in four of six cases in which these firms are fighting to maintain cancer indications for approved drugs. The advisers voted against the companies in two cases.

The staff of the Food and Drug Administration will now consider these votes as they decide what to do regarding the six cases of what they have termed “dangling” accelerated approvals.

“One of the reasons I think we’re convening today is to prevent these accelerated approvals from dangling ad infinitum,” commented one of the members of the advisory panel.

In these cases, companies have been unable to prove the expected benefits that led the FDA to grant accelerated approvals for these indications.

These accelerated approvals, which are often based on surrogate endpoints, such as overall response rates, are granted on the condition that further findings show a clinical benefit – such as in progression-free survival or overall survival – in larger trials.

The FDA tasked its Oncologic Drugs Advisory Committee (ODAC) with conducting the review of the six accelerated approvals for cancer indications at a 3-day meeting (April 27-29).

These reviews were only for specific cancer indications and will not lead to the removal of drugs from the market. These drugs have already been approved for several cancer indications. For example, one of the drugs that was reviewed, pembrolizumab (Keytruda), is approved in the United States for 28 indications.

The FDA is facing growing pains in its efforts to manage the rapidly changing landscape for these immune checkpoint inhibitors. This field of medicine has experienced an “unprecedented level of drug development” in recent years, FDA officials said in briefing materials, owing in part to the agency’s willingness to accept surrogate markers for accelerated approvals. Although some companies have struggled with these, others have built strong cases for the use of their checkpoint inhibitors for these indications.

The ODAC panelists, for example, noted the emergence of nivolumab (Opdivo) as an option for patients with gastric cancer as a reason for seeking to withdraw an indication for pembrolizumab (Keytruda) for this disease.

Just weeks before the meeting, on April 16, the FDA approved nivolumab plus chemotherapy as a first-line treatment for advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. This was a full approval based on data showing an overall survival benefit from a phase 3 trial.
 

Votes by indication

On April 29, the last day of the meeting, the ODAC panel voted 6-2 against maintaining pembrolizumab’s indication as monotherapy for an advanced form of gastric cancer. This was an accelerated approval (granted in 2017) that was based on overall response rates from an open-label trial.

That last day of the meeting also saw another negative vote. On April 29, the ODAC panel voted 5-4 against maintaining an indication for nivolumab in patients with hepatocellular carcinoma (HCC) who were previously treated with sorafenib (Nexavar).

This accelerated approval for nivolumab was granted in 2017. The FDA said it had requested ODAC’s feedback on this indication because of the recent full approval of another checkpoint inhibitor for HCC, atezolizumab (Tecentriq), in combination with bevacizumab (Avastin) for patients with unresectable or metastatic diseases who have not received prior systemic therapy. This full approval (in May 2020) was based on an overall survival benefit.

There was one last vote on the third day of the meeting, and it was positive. The ODAC panel voted 8-0 in favor of maintaining the indication for the use of pembrolizumab as monotherapy for patients with HCC who have previously been treated with sorafenib.

The FDA altered the composition of the ODAC panel during the week, adding members in some cases who had expertise in particular cancers. That led to different totals for the week’s ODAC votes, as shown in the tallies summarized below.

On the first day of the meeting (April 27), the ODAC panel voted 7-2 in favor of maintaining a breast cancer indication for atezolizumab (Tecentriq). This covered use of the immunotherapy in combination with nab-paclitaxel for patients with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1.

The second day of the meeting (April 28) also saw two positive votes. The ODAC panel voted 10-1 for maintaining the indication for atezolizumab for the first-line treatment of cisplatin-ineligible patients with advanced/metastatic urothelial carcinoma, pending final overall survival results from the IMvigor130 trial. The panel also voted 5-3 for maintaining the indication for pembrolizumab in patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1.

The FDA is not bound to follow the voting and recommendations of its advisory panels, but it usually does so.
 

Managing shifts in treatment

In both of the cases in which ODAC voted against maintaining indications, Richard Pazdur, MD, the FDA’s top regulator for cancer medicines, jumped into the debate. Dr. Pazdur countered arguments put forward by representatives of the manufacturers as they sought to maintain indications for their drugs.

Merck officials and representatives argued for pembrolizumab, saying that maintaining the gastric cancer indication might help patients whose disease has progressed despite earlier treatment.

Dr. Pazdur emphasized that the agency would help Merck and physicians to have access to pembrolizumab for these patients even if this one indication were to be withdrawn. But Dr. Pazdur and ODAC members also noted the recent shift in the landscape for gastric cancer, with the recent approval of a new indication for nivolumab.

“I want to emphasize to the patient community out there [that] we firmly believe in the role of checkpoint inhibitors in this disease,” Dr. Pazdur said during the discussion of the indication for pembrolizumab for gastric cancer. “We have to be cognizant of what is the appropriate setting for that, and it currently is in the first line.”

Dr. Pazdur noted that two studies had failed to confirm the expected benefit from pembrolizumab for patients with more advanced disease. Still, if “small numbers” of patients with advanced disease wanted access to Merck’s drug, the FDA and the company could accommodate them. The FDA could delay the removal of the gastric indication to allow patients to continue receiving it. The FDA also could work with physicians on other routes to provide the medicine, such as through single-patient investigational new drug applications or an expanded access program.

“Or Merck can alternatively give the drug gratis to patients,” Dr. Pazdur said.
 

#ProjectFacilitate for expanded access

One of Merck’s speakers at the ODAC meeting, Peter Enzinger, MD, of the Dana-Farber Cancer Institute, Boston, objected to Dr. Pazdur’s plan.

A loss of the gastric indication for pembrolizumab would result in patients with advanced cancer missing out on a chance to try this therapy. Some patients will not have had a chance to try a checkpoint inhibitor earlier in their treatment, and a loss of the indication would cost them that opportunity, he said.

“An expanded-access program sounds very nice, but the reality is that our patients are incredibly sick and that weeks matter,” Dr. Enzinger said, citing administrative hurdles as a barrier to treatment.

“Our patients just don’t have the time for that, and therefore I don’t think an expanded access program is the way to go,” Dr. Enzinger said.

Dr. Pazdur responded to these objections by highlighting an initiative called Project Facilitate at the FDA’s Oncology Center for Excellence. During the meeting, Dr. Pazdur’s division used its @FDAOncology Twitter handle to draw attention to this project.

ODAC panelist Diane Reidy-Lagunes, MD, of Memorial Sloan Kettering Cancer Center, New York, said she had struggled with this vote. She was one of the two panelists to vote in favor of keeping the indication.

“This is also incredibly hard for me. I actually changed it at the last minute,” she said of her vote.

But Dr. Reidy-Lagunes said she was concerned that some patients with advanced disease might not be able to get a checkpoint inhibitor.

“With disparities in healthcare and differences in the way that patients are treated throughout our country, I was nervous that they may not be able to get treated,” she said, noting that she shared her fellow panelists’ doubts about use of pembrolizumab as third-line treatment, owing to negative results in trials.

ODAC member David Mitchell, who served as a consumer representative, also said he found the vote on the gastric indication for pembrolizumab to be a difficult decision.

“As a patient with incurable cancer who’s now being given all three major classes of drugs to treat my disease in combination, these issues really cut close to home,” Mr. Mitchell said.

He said the expectation that the FDA’s expanded access program could help patients with advanced disease try pembrolizumab helped him decide to vote with the 6-2 majority against maintaining this gastric cancer approval.

His vote was based on “the changing treatment landscape.” There is general agreement that the patients in question should receive checkpoint inhibitors as first-line treatment, not third-line treatment, Mr. Mitchell said. The FDA should delay a withdrawal of the approval for pembrolizumab in this case and should allow a transition for those who missed out on treatment with a checkpoint inhibitor earlier in the disease course, he suggested.

“To protect the safety and well-being of patients, we have to base decisions on data,” Mr. Mitchell said. “The data don’t support maintaining the indication” for pembrolizumab.

 

Close split on nivolumab

In contrast to the 6-2 vote against maintaining the pembrolizumab indication, the ODAC panel split more closely, 5-4, on the question of maintaining an indication for the use as monotherapy of nivolumab in HCC.

ODAC panelist Philip C. Hoffman, MD, of the University of Chicago was among those who supported keeping the indication.

“There’s still an unmet need for second-line immunotherapy because there will always be some patients who are poor candidates for bevacizumab or who are not tolerating or responding to sorafenib,” he said.

ODAC panelist Mark A. Lewis, MD, of Intermountain Healthcare, Salt Lake City, said he voted “no” in part because he doubted that Bristol-Myers Squibb would be able to soon produce data for nivolumab that was needed to support this indication.

A version of this article first appeared on Medscape.com.