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Does Intensive Follow-Up Testing Improve Survival in CRC?
TOPLINE:
, according to findings from a secondary analysis.
METHODOLOGY:
- After curative surgery for CRC, intensive patient follow-up is common in clinical practice. However, there’s limited evidence to suggest that more frequent testing provides a long-term survival benefit.
- In the COLOFOL trial, patients with stage II or III CRC who had undergone curative resection were randomly assigned to either high-frequency follow-up (CT scans and CEA screening at 6, 12, 18, 24, and 36 months) or low-frequency follow-up (testing at 12 and 36 months) after surgery.
- This secondary analysis of the COLOFOL trial included 2456 patients (median age, 65 years), 1227 of whom received high-frequency follow-up and 1229 of whom received low-frequency follow-up.
- The main outcome of the secondary analysis was 10-year overall mortality and CRC–specific mortality rates.
- The analysis included both intention-to-treat and per-protocol approaches, with outcomes measured through December 2020.
TAKEAWAY:
- In the intention-to-treat analysis, the 10-year overall mortality rates were similar between the high- and low-frequency follow-up groups — 27.1% and 28.4%, respectively (risk difference, 1.3%; P = .46).
- A per-protocol analysis confirmed these findings: The 10-year overall mortality risk was 26.4% in the high-frequency group and 27.8% in the low-frequency group.
- The 10-year CRC–specific mortality rate was also similar between the high-frequency and low-frequency groups — 15.6% and 16.0%, respectively — (risk difference, 0.4%; P = .72). The same pattern was seen in the per-protocol analysis, which found a 10-year CRC–specific mortality risk of 15.6% in the high-frequency group and 15.9% in the low-frequency group.
- Subgroup analyses by cancer stage and location (rectal and colon) also revealed no significant differences in mortality outcomes between the two follow-up groups.
IN PRACTICE:
“This secondary analysis of the COLOFOL randomized clinical trial found that, among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scan and CEA screening, compared with less frequent follow-up, did not result in a significant rate reduction in 10-year overall mortality or colorectal cancer-specific mortality,” the authors concluded. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”
SOURCE:
The study, led by Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Aarhus University Hospital and Aarhus University, Aarhus, Denmark, was published online in JAMA Network Open.
LIMITATIONS:
The staff turnover at recruitment centers potentially affected protocol adherence. The inability to blind patients and physicians to the follow-up frequency was another limitation. The low-frequency follow-up protocol was less intensive than that recommended in the current guidelines by the National Comprehensive Cancer Network and the American Society of Clinical Oncology, potentially limiting comparisons to current standard practices.
DISCLOSURES:
The initial trial received unrestricted grants from multiple organizations including the Nordic Cancer Union, A.P. Møller Foundation, Beckett Foundation, Danish Cancer Society, and Swedish Cancer Foundation project. The authors reported no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
, according to findings from a secondary analysis.
METHODOLOGY:
- After curative surgery for CRC, intensive patient follow-up is common in clinical practice. However, there’s limited evidence to suggest that more frequent testing provides a long-term survival benefit.
- In the COLOFOL trial, patients with stage II or III CRC who had undergone curative resection were randomly assigned to either high-frequency follow-up (CT scans and CEA screening at 6, 12, 18, 24, and 36 months) or low-frequency follow-up (testing at 12 and 36 months) after surgery.
- This secondary analysis of the COLOFOL trial included 2456 patients (median age, 65 years), 1227 of whom received high-frequency follow-up and 1229 of whom received low-frequency follow-up.
- The main outcome of the secondary analysis was 10-year overall mortality and CRC–specific mortality rates.
- The analysis included both intention-to-treat and per-protocol approaches, with outcomes measured through December 2020.
TAKEAWAY:
- In the intention-to-treat analysis, the 10-year overall mortality rates were similar between the high- and low-frequency follow-up groups — 27.1% and 28.4%, respectively (risk difference, 1.3%; P = .46).
- A per-protocol analysis confirmed these findings: The 10-year overall mortality risk was 26.4% in the high-frequency group and 27.8% in the low-frequency group.
- The 10-year CRC–specific mortality rate was also similar between the high-frequency and low-frequency groups — 15.6% and 16.0%, respectively — (risk difference, 0.4%; P = .72). The same pattern was seen in the per-protocol analysis, which found a 10-year CRC–specific mortality risk of 15.6% in the high-frequency group and 15.9% in the low-frequency group.
- Subgroup analyses by cancer stage and location (rectal and colon) also revealed no significant differences in mortality outcomes between the two follow-up groups.
IN PRACTICE:
“This secondary analysis of the COLOFOL randomized clinical trial found that, among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scan and CEA screening, compared with less frequent follow-up, did not result in a significant rate reduction in 10-year overall mortality or colorectal cancer-specific mortality,” the authors concluded. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”
SOURCE:
The study, led by Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Aarhus University Hospital and Aarhus University, Aarhus, Denmark, was published online in JAMA Network Open.
LIMITATIONS:
The staff turnover at recruitment centers potentially affected protocol adherence. The inability to blind patients and physicians to the follow-up frequency was another limitation. The low-frequency follow-up protocol was less intensive than that recommended in the current guidelines by the National Comprehensive Cancer Network and the American Society of Clinical Oncology, potentially limiting comparisons to current standard practices.
DISCLOSURES:
The initial trial received unrestricted grants from multiple organizations including the Nordic Cancer Union, A.P. Møller Foundation, Beckett Foundation, Danish Cancer Society, and Swedish Cancer Foundation project. The authors reported no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
TOPLINE:
, according to findings from a secondary analysis.
METHODOLOGY:
- After curative surgery for CRC, intensive patient follow-up is common in clinical practice. However, there’s limited evidence to suggest that more frequent testing provides a long-term survival benefit.
- In the COLOFOL trial, patients with stage II or III CRC who had undergone curative resection were randomly assigned to either high-frequency follow-up (CT scans and CEA screening at 6, 12, 18, 24, and 36 months) or low-frequency follow-up (testing at 12 and 36 months) after surgery.
- This secondary analysis of the COLOFOL trial included 2456 patients (median age, 65 years), 1227 of whom received high-frequency follow-up and 1229 of whom received low-frequency follow-up.
- The main outcome of the secondary analysis was 10-year overall mortality and CRC–specific mortality rates.
- The analysis included both intention-to-treat and per-protocol approaches, with outcomes measured through December 2020.
TAKEAWAY:
- In the intention-to-treat analysis, the 10-year overall mortality rates were similar between the high- and low-frequency follow-up groups — 27.1% and 28.4%, respectively (risk difference, 1.3%; P = .46).
- A per-protocol analysis confirmed these findings: The 10-year overall mortality risk was 26.4% in the high-frequency group and 27.8% in the low-frequency group.
- The 10-year CRC–specific mortality rate was also similar between the high-frequency and low-frequency groups — 15.6% and 16.0%, respectively — (risk difference, 0.4%; P = .72). The same pattern was seen in the per-protocol analysis, which found a 10-year CRC–specific mortality risk of 15.6% in the high-frequency group and 15.9% in the low-frequency group.
- Subgroup analyses by cancer stage and location (rectal and colon) also revealed no significant differences in mortality outcomes between the two follow-up groups.
IN PRACTICE:
“This secondary analysis of the COLOFOL randomized clinical trial found that, among patients with stage II or III colorectal cancer, more frequent follow-up testing with CT scan and CEA screening, compared with less frequent follow-up, did not result in a significant rate reduction in 10-year overall mortality or colorectal cancer-specific mortality,” the authors concluded. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”
SOURCE:
The study, led by Henrik Toft Sørensen, MD, PhD, DMSc, DSc, Aarhus University Hospital and Aarhus University, Aarhus, Denmark, was published online in JAMA Network Open.
LIMITATIONS:
The staff turnover at recruitment centers potentially affected protocol adherence. The inability to blind patients and physicians to the follow-up frequency was another limitation. The low-frequency follow-up protocol was less intensive than that recommended in the current guidelines by the National Comprehensive Cancer Network and the American Society of Clinical Oncology, potentially limiting comparisons to current standard practices.
DISCLOSURES:
The initial trial received unrestricted grants from multiple organizations including the Nordic Cancer Union, A.P. Møller Foundation, Beckett Foundation, Danish Cancer Society, and Swedish Cancer Foundation project. The authors reported no relevant conflicts of interest.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.
Some Antihypertensives Linked to HCC Risk in Patients With MASLD and Cirrhosis
SAN DIEGO — according to new research.
In particular, the use of calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) was associated with a higher risk of developing HCC, compared with not using these medications.
About half of patients with MASLD have hypertension, and the use of antihypertensives in these patients is beneficial to reduce the risk for cardiovascular disease and complications related to MASLD, said lead author Ahmed Elhariri, MD, a research fellow at the University of Texas MD Anderson Cancer Center, Houston, who conducted the study as a research assistant in gastroenterology and hepatology at the Baylor College of Medicine, also in Houston.
However, previous studies have suggested a possible link between these medications and cancer development, “especially CCBs and breast and lung cancer,” said Elhariri, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Analyzing Potential Risks
In a case-control study, Elhariri and colleagues analyzed antihypertensive medication use among patients with MASLD-induced HCC, as defined by histology or radiology based on the Liver Imaging Reporting & Data System, and control patients with MASLD but without HCC.
Between 2020 and 2024, the research team recruited 153 newly diagnosed HCC cases with different etiologies and 170 patients with MASLD but without HCC from Baylor College of Medicine’s outpatient clinics. For this study, they selected 47 age- and sex-matched pairs, all of whom had cirrhosis. Only those with a history of hypertension were included, however. Data on risk factors of metabolic syndrome (including diabetes) and HCC were collected, along with details about medication use such as metformin and statins.
A total of 42 patients with MASLD and HCC and 39 MASLD control individuals had a history of hypertension and were treated with antihypertensive medications. The mean age was 66.5 years for the HCC group and 63.5 years for the control group, and the mean body mass index (BMI) was 31.1 for the HCC group and 31.7 for the control group.
After adjusting for age, sex, BMI, Hispanic ethnicity, and use of other medications, patients taking CCBs had an increased HCC risk (odds ratio [OR], 2.76), compared with those not taking CCBs. Patients taking ACE inhibitors or ARBs also had an increased HCC risk (OR, 2.54), compared with those not taking ACE inhibitors or ARBs.
However, there wasn’t a statistically significant difference in HCC risk among patients taking beta-blockers (OR, 0.87).
“Patients with fatty liver in the presence of metabolic syndrome, especially in the presence of cirrhosis and antihypertensives, need to have stricter surveillance for liver cancer,” Elhariri said.
“We need to carefully review blood pressure medications in patients with MASLD and cirrhosis,” he said. CCBs, ACE inhibitors, and ARBs can be replaced with beta-blockers, “which have been shown to reduce progression of cirrhosis-related complications.”
Considering Clinical Implications
“Although our study showed some association between the use of some commonly used antihypertensives and the risk for HCC in this high-risk population, it is based on data collected retrospectively on a small number of selected patients with advanced liver disease,” Elhariri noted.
The associations and underlying mechanisms should be studied in larger populations and prospective trials, he said. “Until we have more data with a significantly larger sample size, it’s premature to raise the concern in the general population.”
“The cardiovascular benefits of controlling blood pressure far outweigh the risk of liver cancer in patients with metabolic syndrome,” Elhariri added.
In ongoing studies, researchers are investigating ways to improve patient outcomes and reduce the negative effects of cirrhosis-associated complications among patients with MASLD and metabolic dysfunction–associated steatohepatitis (MASH), Muhammad Ali Butt, MD, a hepatology fellow at Beth Israel Lahey Hospital & Medical Center in Burlington, Massachusetts, said in an interview.
Butt, who wasn’t involved with this study, presented separate research on statins in MASH patients with cirrhosis, which indicated statistically significant decreases in portal hypertension, thrombosis, hepatorenal syndrome, hepatic encephalopathy, and mortality.
“We know patients with MASLD- and MASH-associated cirrhosis commonly have other comorbidities, including high cardiovascular risks, diabetes, and hyperlipidemia,” he said. “All of these conditions indicate patients to be on other medications such as antihypertensives or statins. It’s important to know the role these medications play, especially given the high-risk profile of these patients.”
Elhariri and Butt reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
SAN DIEGO — according to new research.
In particular, the use of calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) was associated with a higher risk of developing HCC, compared with not using these medications.
About half of patients with MASLD have hypertension, and the use of antihypertensives in these patients is beneficial to reduce the risk for cardiovascular disease and complications related to MASLD, said lead author Ahmed Elhariri, MD, a research fellow at the University of Texas MD Anderson Cancer Center, Houston, who conducted the study as a research assistant in gastroenterology and hepatology at the Baylor College of Medicine, also in Houston.
However, previous studies have suggested a possible link between these medications and cancer development, “especially CCBs and breast and lung cancer,” said Elhariri, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Analyzing Potential Risks
In a case-control study, Elhariri and colleagues analyzed antihypertensive medication use among patients with MASLD-induced HCC, as defined by histology or radiology based on the Liver Imaging Reporting & Data System, and control patients with MASLD but without HCC.
Between 2020 and 2024, the research team recruited 153 newly diagnosed HCC cases with different etiologies and 170 patients with MASLD but without HCC from Baylor College of Medicine’s outpatient clinics. For this study, they selected 47 age- and sex-matched pairs, all of whom had cirrhosis. Only those with a history of hypertension were included, however. Data on risk factors of metabolic syndrome (including diabetes) and HCC were collected, along with details about medication use such as metformin and statins.
A total of 42 patients with MASLD and HCC and 39 MASLD control individuals had a history of hypertension and were treated with antihypertensive medications. The mean age was 66.5 years for the HCC group and 63.5 years for the control group, and the mean body mass index (BMI) was 31.1 for the HCC group and 31.7 for the control group.
After adjusting for age, sex, BMI, Hispanic ethnicity, and use of other medications, patients taking CCBs had an increased HCC risk (odds ratio [OR], 2.76), compared with those not taking CCBs. Patients taking ACE inhibitors or ARBs also had an increased HCC risk (OR, 2.54), compared with those not taking ACE inhibitors or ARBs.
However, there wasn’t a statistically significant difference in HCC risk among patients taking beta-blockers (OR, 0.87).
“Patients with fatty liver in the presence of metabolic syndrome, especially in the presence of cirrhosis and antihypertensives, need to have stricter surveillance for liver cancer,” Elhariri said.
“We need to carefully review blood pressure medications in patients with MASLD and cirrhosis,” he said. CCBs, ACE inhibitors, and ARBs can be replaced with beta-blockers, “which have been shown to reduce progression of cirrhosis-related complications.”
Considering Clinical Implications
“Although our study showed some association between the use of some commonly used antihypertensives and the risk for HCC in this high-risk population, it is based on data collected retrospectively on a small number of selected patients with advanced liver disease,” Elhariri noted.
The associations and underlying mechanisms should be studied in larger populations and prospective trials, he said. “Until we have more data with a significantly larger sample size, it’s premature to raise the concern in the general population.”
“The cardiovascular benefits of controlling blood pressure far outweigh the risk of liver cancer in patients with metabolic syndrome,” Elhariri added.
In ongoing studies, researchers are investigating ways to improve patient outcomes and reduce the negative effects of cirrhosis-associated complications among patients with MASLD and metabolic dysfunction–associated steatohepatitis (MASH), Muhammad Ali Butt, MD, a hepatology fellow at Beth Israel Lahey Hospital & Medical Center in Burlington, Massachusetts, said in an interview.
Butt, who wasn’t involved with this study, presented separate research on statins in MASH patients with cirrhosis, which indicated statistically significant decreases in portal hypertension, thrombosis, hepatorenal syndrome, hepatic encephalopathy, and mortality.
“We know patients with MASLD- and MASH-associated cirrhosis commonly have other comorbidities, including high cardiovascular risks, diabetes, and hyperlipidemia,” he said. “All of these conditions indicate patients to be on other medications such as antihypertensives or statins. It’s important to know the role these medications play, especially given the high-risk profile of these patients.”
Elhariri and Butt reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
SAN DIEGO — according to new research.
In particular, the use of calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) was associated with a higher risk of developing HCC, compared with not using these medications.
About half of patients with MASLD have hypertension, and the use of antihypertensives in these patients is beneficial to reduce the risk for cardiovascular disease and complications related to MASLD, said lead author Ahmed Elhariri, MD, a research fellow at the University of Texas MD Anderson Cancer Center, Houston, who conducted the study as a research assistant in gastroenterology and hepatology at the Baylor College of Medicine, also in Houston.
However, previous studies have suggested a possible link between these medications and cancer development, “especially CCBs and breast and lung cancer,” said Elhariri, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).
Analyzing Potential Risks
In a case-control study, Elhariri and colleagues analyzed antihypertensive medication use among patients with MASLD-induced HCC, as defined by histology or radiology based on the Liver Imaging Reporting & Data System, and control patients with MASLD but without HCC.
Between 2020 and 2024, the research team recruited 153 newly diagnosed HCC cases with different etiologies and 170 patients with MASLD but without HCC from Baylor College of Medicine’s outpatient clinics. For this study, they selected 47 age- and sex-matched pairs, all of whom had cirrhosis. Only those with a history of hypertension were included, however. Data on risk factors of metabolic syndrome (including diabetes) and HCC were collected, along with details about medication use such as metformin and statins.
A total of 42 patients with MASLD and HCC and 39 MASLD control individuals had a history of hypertension and were treated with antihypertensive medications. The mean age was 66.5 years for the HCC group and 63.5 years for the control group, and the mean body mass index (BMI) was 31.1 for the HCC group and 31.7 for the control group.
After adjusting for age, sex, BMI, Hispanic ethnicity, and use of other medications, patients taking CCBs had an increased HCC risk (odds ratio [OR], 2.76), compared with those not taking CCBs. Patients taking ACE inhibitors or ARBs also had an increased HCC risk (OR, 2.54), compared with those not taking ACE inhibitors or ARBs.
However, there wasn’t a statistically significant difference in HCC risk among patients taking beta-blockers (OR, 0.87).
“Patients with fatty liver in the presence of metabolic syndrome, especially in the presence of cirrhosis and antihypertensives, need to have stricter surveillance for liver cancer,” Elhariri said.
“We need to carefully review blood pressure medications in patients with MASLD and cirrhosis,” he said. CCBs, ACE inhibitors, and ARBs can be replaced with beta-blockers, “which have been shown to reduce progression of cirrhosis-related complications.”
Considering Clinical Implications
“Although our study showed some association between the use of some commonly used antihypertensives and the risk for HCC in this high-risk population, it is based on data collected retrospectively on a small number of selected patients with advanced liver disease,” Elhariri noted.
The associations and underlying mechanisms should be studied in larger populations and prospective trials, he said. “Until we have more data with a significantly larger sample size, it’s premature to raise the concern in the general population.”
“The cardiovascular benefits of controlling blood pressure far outweigh the risk of liver cancer in patients with metabolic syndrome,” Elhariri added.
In ongoing studies, researchers are investigating ways to improve patient outcomes and reduce the negative effects of cirrhosis-associated complications among patients with MASLD and metabolic dysfunction–associated steatohepatitis (MASH), Muhammad Ali Butt, MD, a hepatology fellow at Beth Israel Lahey Hospital & Medical Center in Burlington, Massachusetts, said in an interview.
Butt, who wasn’t involved with this study, presented separate research on statins in MASH patients with cirrhosis, which indicated statistically significant decreases in portal hypertension, thrombosis, hepatorenal syndrome, hepatic encephalopathy, and mortality.
“We know patients with MASLD- and MASH-associated cirrhosis commonly have other comorbidities, including high cardiovascular risks, diabetes, and hyperlipidemia,” he said. “All of these conditions indicate patients to be on other medications such as antihypertensives or statins. It’s important to know the role these medications play, especially given the high-risk profile of these patients.”
Elhariri and Butt reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
FROM AASLD 2024
New Cancer Drugs: Do Patients Prefer Faster Access or Clinical Benefit?
When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them.
The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials.
During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities.
In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.
Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.
But is that really the case?
The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works.
In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios.
The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).
The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).
The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios.
Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty.
Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.
“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.
Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview.
In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.
“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.
Bishal Gyawali, MD, PhD, was not surprised by the findings.
“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview.
“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”
However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added.
What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.
The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.
A version of this article first appeared on Medscape.com.
When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them.
The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials.
During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities.
In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.
Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.
But is that really the case?
The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works.
In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios.
The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).
The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).
The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios.
Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty.
Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.
“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.
Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview.
In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.
“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.
Bishal Gyawali, MD, PhD, was not surprised by the findings.
“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview.
“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”
However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added.
What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.
The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.
A version of this article first appeared on Medscape.com.
When the Food and Drug Administration (FDA) grants cancer drugs accelerated approval, a key aim is to provide patients faster access to therapies that can benefit them.
The downside of a speedier approval timeline, however, is that it’s often not yet clear whether the new drugs will actually allow a patient to live longer or better. Information on overall survival and quality of life typically comes years later, after drugs undergo confirmatory trials, or sometimes not at all, if companies fail to conduct these trials.
During this waiting period, patients may be receiving a cancer drug that provides no real clinical benefit but comes with a host of toxicities.
In fact, the odds are about as good as a coin flip. For cancer drugs that have confirmatory trial data, more than half don’t ultimately provide an overall survival or quality of life benefit.
Inherent to the accelerated approval process is the assumption that patients are willing to accept this uncertainty in exchange for faster access.
But is that really the case?
The researchers asked about 870 adults with experience of cancer challenges — either their own cancer diagnosis or that of family or a close friend — whether they valued faster access or certainty that a drug really works.
In the study, participants imagined they had been diagnosed with cancer and could choose between two cancer drugs under investigation in clinical trials but with uncertain effectiveness, and a current standard treatment. Participants had to make a series of choices based on five scenarios.
The first two scenarios were based on the impact of the current standard treatment: A patient’s life expectancy on the standard treatment (6 months up to 3 years), and a patient’s physical health on the standard treatment (functional status restricted only during strenuous activities up to completely disabled).
The remaining three scenarios dealt with the two new drugs: The effect of the new drugs on a surrogate endpoint, progression-free survival (whether the drugs slowed tumor growth for an extra month or 5 additional months compared with the standard treatment), certainty that slowing tumor growth will improve survival (very low to high), and the wait time to access the drugs (immediately to as long as 2 years).
The researchers assessed the relative importance of survival benefit certainty vs wait time and how that balance shifted depending on the different scenarios.
Overall, the researchers found that, if there was no evidence linking the surrogate endpoint (progression-free survival) to overall survival, patients were willing to wait about 8 months for weak evidence of an overall survival benefit (ie, low certainty the drug will extend survival by 1-5 months), about 16 months for moderate certainty, and almost 22 months for high certainty.
Despite a willingness to wait for greater certainty, participants did value speed as well. Overall, respondents showed a strong preference against a 1-year delay in FDA approval time. People who were aged 55 years or more and were non-White individuals made less than $40,000 year as well as those with the lowest life expectancy on a current standard treatment were most sensitive to wait times while those with better functional status and longer life expectancies on a current treatment were less sensitive to longer wait times.
“Our results indicate that some patients (except those with the poorest prognoses) would find the additional time required to generate evidence on the survival benefit of new cancer drugs an acceptable tradeoff,” the study authors concluded.
Although people do place high value on timely access to new cancer drugs, especially if there are limited treatment options, many are willing to wait for greater certainty that a new drug provides an overall survival benefit, lead author Robin Forrest, MSc, with the Department of Health Policy, London School of Economics in England, said in an interview.
In the study, respondents also did not place significant value on whether the drug substantially slowed cancer growth. “In other words, substantial progression-free survival benefit of a drug did not compensate for lack of certainty about a drug’s benefit on survival in respondents’ drug choices,” the authors explained.
“In an effort to move quickly, we have accepted progression-free survival [as a surrogate endpoint],” Jyoti D. Patel, MD, oncologist with Northwestern Memorial Hospital, Chicago, Illinois, who wasn’t involved in the study. But a growing body of evidence indicates that progression-free survival is often a poor surrogate for overall survival. And what this study suggests is that “patients uniformly care about improvements in overall survival and the quality of that survival,” Patel said.
Bishal Gyawali, MD, PhD, was not surprised by the findings.
“I always thought this was the real-world scenario, but the problem is the voices of ordinary patients are not heard,” Gyawali, with Queen’s University, Kingston, Ontario, Canada, who also wasn’t involved in the study, said in an interview.
“What is heard is the loud noise of ‘we need access now, today, yesterday’ — ‘we don’t care if the drug doesn’t improve overall survival, we just need a drug, any drug’ — ‘we don’t care how much it costs, we need access today,’ ” Gyawali said. “Not saying this is wrong, but this is not the representation of all patients.”
However, the voices of patients who are more cautious and want evidence of benefit before accepting toxicities don’t make headlines, he added.
What this survey means from a policy perspective, said Gyawali, is that accelerated approvals that do not mandate survival endpoint in confirmatory trials are ignoring the need of many patients who prioritize certainty of benefit over speed of access.
The study was funded by the London School of Economics and Political Science Phelan United States Centre. Forrest had no relevant disclosures. Gyawali has received consulting fees from Vivio Health. Patel has various relationships with AbbVie, Anheart, AstraZeneca, Bristol-Myers Squibb, Guardant, Tempus, Sanofi, BluePrint, Takeda, and Gilead.
A version of this article first appeared on Medscape.com.
FROM THE LANCET ONCOLOGY
Could Diet and Gut Bacteria Be Fueling Early CRC?
This transcript has been edited for clarity.
I’d like to reflect a little on the ever-rising incidence of early-onset colorectal cancer. I saw two patients in the clinic on Friday, both in their early thirties, presenting with stage IV disease. Both had young families — a disaster.
This is an issue that we must address, I think, epidemiologically. We know that and currently, around 200,000 such cases are diagnosed every year, but it is said to increase unquestionably.
The epidemiologists, I think, correctly have identified that this sharp, rapid increase does imply that there is a new environmental change that is underpinning or underscoring this rise in early-onset disease.
There’s a fantastic team that has been put together by Paul Brennan, Mike Stratton, and colleagues, a collaborative group of epidemiologists, geneticists, and bioinformaticians, who are looking at a global study to try to understand the basis of early-onset colorectal cancer. Their approach is to combine conventional epidemiology, genomics, and fantastic computational support to try to unpick the mutational signatures involved.
The dominant hypothesis is that, over the past 20-25 years or so, there has been a change in diet that has allowed an alteration in the gut microbiome such that we now harbor, in some cases, more bacteria capable of manufacturing, synthesizing, and releasing mutagenic chemicals. There’s a subtype of Escherichia coli which manufactures one such mutagen called colibactin.
Again, through some of the painstaking, extraordinary work that Mike Stratton and colleagues have done at the Sanger Institute, they have managed to, using a variety of different techniques — in vitro, observational, and so on — relate exposure to the mutagen colibactin to a particular mutational signature.
They plan to do a large global study — one of the strengths — involving many different countries around the globe, collect material from older colorectal cancer patients and early-onset colorectal cancer patients, and undertake a staggeringly large mutational study to see if the mutational signature associated with colibactin is more highly represented in these early-onset cases. The hypothesis is that, if you’re exposed to this mutagen in childhood, then it increases the tumor mutational burden and therefore the likelihood of developing cancer at an earlier age.
All of us believe that converting a normal cell into a tumor cell usually requires five or six or seven separate mutational events occurring at random. The earlier these occur, the greater the tumor, the greater the normal single-cellular mutational burden, and the more likely it is to develop cancer sooner rather than later.
This is a fantastically interesting study, and it’s the way ahead with modern genetic epidemiology, one would say. We wish them well. This will be a 3- to 5-year truly international effort, bringing together a genuinely internationally outstanding research team. We hope that they are able to shed more light on the epidemiology of this early-onset disease, because only by understanding can we deflect and deal with it.
Knowledge is power, as I’ve said many times before. If we understand the underlying epidemiology, that will allow us to intervene, one would hope, and avoid the chaotic disaster of my clinic on Friday, with these two young patients with an extremely limited lifespan and large families who will be left bereft in having lost a parent.
More power to the team. We wish them well with the study, but again, this is a pointer to the future, one would hope, of modern genetic computational epidemiology.
I’d be really interested in any ideas or comments that you might have. Are you in the field? Are you seeing more young patients? Do you have any ideas or hypotheses of your own around the microbiome and what bugs might be involved and so on?
Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford, England; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, has disclosed relevant financial relationships with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer, Genomic Health, Merck Serono, and Roche.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I’d like to reflect a little on the ever-rising incidence of early-onset colorectal cancer. I saw two patients in the clinic on Friday, both in their early thirties, presenting with stage IV disease. Both had young families — a disaster.
This is an issue that we must address, I think, epidemiologically. We know that and currently, around 200,000 such cases are diagnosed every year, but it is said to increase unquestionably.
The epidemiologists, I think, correctly have identified that this sharp, rapid increase does imply that there is a new environmental change that is underpinning or underscoring this rise in early-onset disease.
There’s a fantastic team that has been put together by Paul Brennan, Mike Stratton, and colleagues, a collaborative group of epidemiologists, geneticists, and bioinformaticians, who are looking at a global study to try to understand the basis of early-onset colorectal cancer. Their approach is to combine conventional epidemiology, genomics, and fantastic computational support to try to unpick the mutational signatures involved.
The dominant hypothesis is that, over the past 20-25 years or so, there has been a change in diet that has allowed an alteration in the gut microbiome such that we now harbor, in some cases, more bacteria capable of manufacturing, synthesizing, and releasing mutagenic chemicals. There’s a subtype of Escherichia coli which manufactures one such mutagen called colibactin.
Again, through some of the painstaking, extraordinary work that Mike Stratton and colleagues have done at the Sanger Institute, they have managed to, using a variety of different techniques — in vitro, observational, and so on — relate exposure to the mutagen colibactin to a particular mutational signature.
They plan to do a large global study — one of the strengths — involving many different countries around the globe, collect material from older colorectal cancer patients and early-onset colorectal cancer patients, and undertake a staggeringly large mutational study to see if the mutational signature associated with colibactin is more highly represented in these early-onset cases. The hypothesis is that, if you’re exposed to this mutagen in childhood, then it increases the tumor mutational burden and therefore the likelihood of developing cancer at an earlier age.
All of us believe that converting a normal cell into a tumor cell usually requires five or six or seven separate mutational events occurring at random. The earlier these occur, the greater the tumor, the greater the normal single-cellular mutational burden, and the more likely it is to develop cancer sooner rather than later.
This is a fantastically interesting study, and it’s the way ahead with modern genetic epidemiology, one would say. We wish them well. This will be a 3- to 5-year truly international effort, bringing together a genuinely internationally outstanding research team. We hope that they are able to shed more light on the epidemiology of this early-onset disease, because only by understanding can we deflect and deal with it.
Knowledge is power, as I’ve said many times before. If we understand the underlying epidemiology, that will allow us to intervene, one would hope, and avoid the chaotic disaster of my clinic on Friday, with these two young patients with an extremely limited lifespan and large families who will be left bereft in having lost a parent.
More power to the team. We wish them well with the study, but again, this is a pointer to the future, one would hope, of modern genetic computational epidemiology.
I’d be really interested in any ideas or comments that you might have. Are you in the field? Are you seeing more young patients? Do you have any ideas or hypotheses of your own around the microbiome and what bugs might be involved and so on?
Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford, England; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, has disclosed relevant financial relationships with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer, Genomic Health, Merck Serono, and Roche.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
I’d like to reflect a little on the ever-rising incidence of early-onset colorectal cancer. I saw two patients in the clinic on Friday, both in their early thirties, presenting with stage IV disease. Both had young families — a disaster.
This is an issue that we must address, I think, epidemiologically. We know that and currently, around 200,000 such cases are diagnosed every year, but it is said to increase unquestionably.
The epidemiologists, I think, correctly have identified that this sharp, rapid increase does imply that there is a new environmental change that is underpinning or underscoring this rise in early-onset disease.
There’s a fantastic team that has been put together by Paul Brennan, Mike Stratton, and colleagues, a collaborative group of epidemiologists, geneticists, and bioinformaticians, who are looking at a global study to try to understand the basis of early-onset colorectal cancer. Their approach is to combine conventional epidemiology, genomics, and fantastic computational support to try to unpick the mutational signatures involved.
The dominant hypothesis is that, over the past 20-25 years or so, there has been a change in diet that has allowed an alteration in the gut microbiome such that we now harbor, in some cases, more bacteria capable of manufacturing, synthesizing, and releasing mutagenic chemicals. There’s a subtype of Escherichia coli which manufactures one such mutagen called colibactin.
Again, through some of the painstaking, extraordinary work that Mike Stratton and colleagues have done at the Sanger Institute, they have managed to, using a variety of different techniques — in vitro, observational, and so on — relate exposure to the mutagen colibactin to a particular mutational signature.
They plan to do a large global study — one of the strengths — involving many different countries around the globe, collect material from older colorectal cancer patients and early-onset colorectal cancer patients, and undertake a staggeringly large mutational study to see if the mutational signature associated with colibactin is more highly represented in these early-onset cases. The hypothesis is that, if you’re exposed to this mutagen in childhood, then it increases the tumor mutational burden and therefore the likelihood of developing cancer at an earlier age.
All of us believe that converting a normal cell into a tumor cell usually requires five or six or seven separate mutational events occurring at random. The earlier these occur, the greater the tumor, the greater the normal single-cellular mutational burden, and the more likely it is to develop cancer sooner rather than later.
This is a fantastically interesting study, and it’s the way ahead with modern genetic epidemiology, one would say. We wish them well. This will be a 3- to 5-year truly international effort, bringing together a genuinely internationally outstanding research team. We hope that they are able to shed more light on the epidemiology of this early-onset disease, because only by understanding can we deflect and deal with it.
Knowledge is power, as I’ve said many times before. If we understand the underlying epidemiology, that will allow us to intervene, one would hope, and avoid the chaotic disaster of my clinic on Friday, with these two young patients with an extremely limited lifespan and large families who will be left bereft in having lost a parent.
More power to the team. We wish them well with the study, but again, this is a pointer to the future, one would hope, of modern genetic computational epidemiology.
I’d be really interested in any ideas or comments that you might have. Are you in the field? Are you seeing more young patients? Do you have any ideas or hypotheses of your own around the microbiome and what bugs might be involved and so on?
Dr. Kerr, Professor, Nuffield Department of Clinical Laboratory Science, University of Oxford, England; Professor of Cancer Medicine, Oxford Cancer Centre, Oxford, United Kingdom, has disclosed relevant financial relationships with Celleron Therapeutics, Oxford Cancer Biomarkers, Afrox, GlaxoSmithKline, Bayer, Genomic Health, Merck Serono, and Roche.
A version of this article appeared on Medscape.com.
New Cancer Vaccines on the Horizon: Renewed Hope or Hype?
Vaccines for treating and preventing cancer have long been considered a holy grail in oncology.
But aside from a few notable exceptions — including the human papillomavirus (HPV) vaccine, which has dramatically reduced the incidence of HPV-related cancers, and a Bacillus Calmette-Guerin vaccine, which helps prevent early-stage bladder cancer recurrence — most have failed to deliver.
Following a string of disappointments over the past decade, recent advances in the immunotherapy space are bringing renewed hope for progress.
In an American Association for Cancer Research (AACR) series earlier in 2024, Catherine J. Wu, MD, predicted big strides for cancer vaccines, especially for personalized vaccines that target patient-specific neoantigens — the proteins that form on cancer cells — as well as vaccines that can treat diverse tumor types.
said Wu, the Lavine Family Chair of Preventative Cancer Therapies at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.
A prime example is a personalized, messenger RNA (mRNA)–based vaccine designed to prevent melanoma recurrence. The mRNA-4157 vaccine encodes up to 34 different patient-specific neoantigens.
“This is one of the most exciting developments in modern cancer therapy,” said Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, Coventry, England, who commented on the investigational vaccine via the UK-based Science Media Centre.
Other promising options are on the horizon as well. In August, BioNTech announced a phase 1 global trial to study BNT116 — a vaccine to treat non–small cell lung cancer (NSCLC). BNT116, like mRNA-4157, targets specific antigens in the lung cancer cells.
“This technology is the next big phase of cancer treatment,” Siow Ming Lee, MD, a consultant medical oncologist at University College London Hospitals in England, which is leading the UK trial for the lung cancer and melanoma vaccines, told The Guardian. “We are now entering this very exciting new era of mRNA-based immunotherapy clinical trials to investigate the treatment of lung cancer.”
Still, these predictions have a familiar ring. While the prospects are exciting, delivering on them is another story. There are simply no guarantees these strategies will work as hoped.
Then: Where We Were
Cancer vaccine research began to ramp up in the 2000s, and in 2006, the first-generation HPV vaccine, Gardasil, was approved. Gardasil prevents infection from four strains of HPV that cause about 80% of cervical cancer cases.
In 2010, the Food and Drug Administration approved sipuleucel-T, the first therapeutic cancer vaccine, which improved overall survival in patients with hormone-refractory prostate cancer.
Researchers predicted this approval would “pave the way for developing innovative, next generation of vaccines with enhanced antitumor potency.”
In a 2015 AACR research forecast report, Drew Pardoll, MD, PhD, co-director of the Cancer Immunology and Hematopoiesis Program at Johns Hopkins University, Baltimore, Maryland, said that “we can expect to see encouraging results from studies using cancer vaccines.”
Despite the excitement surrounding cancer vaccines alongside a few successes, the next decade brought a longer string of late-phase disappointments.
In 2016, the phase 3 ACT IV trial of a therapeutic vaccine to treat glioblastoma multiforme (CDX-110) was terminated after it failed to demonstrate improved survival.
In 2017, a phase 3 trial of the therapeutic pancreatic cancer vaccine, GVAX, was stopped early for lack of efficacy.
That year, an attenuated Listeria monocytogenes vaccine to treat pancreatic cancer and mesothelioma also failed to come to fruition. In late 2017, concerns over listeria infections prompted Aduro Biotech to cancel its listeria-based cancer treatment program.
In 2018, a phase 3 trial of belagenpumatucel-L, a therapeutic NSCLC vaccine, failed to demonstrate a significant improvement in survival and further study was discontinued.
And in 2019, a vaccine targeting MAGE-A3, a cancer-testis antigen present in multiple tumor types, failed to meet endpoints for improved survival in a phase 3 trial, leading to discontinuation of the vaccine program.
But these disappointments and failures are normal parts of medical research and drug development and have allowed for incremental advances that helped fuel renewed interest and hope for cancer vaccines, when the timing was right, explained vaccine pioneer Larry W. Kwak, MD, PhD, deputy director of the Comprehensive Cancer Center at City of Hope, Duarte, California.
When it comes to vaccine progress, timing makes a difference. In 2011, Kwak and colleagues published promising phase 3 trial results on a personalized vaccine. The vaccine was a patient-specific tumor-derived antigen for patients with follicular lymphoma in their first remission following chemotherapy. Patients who received the vaccine demonstrated significantly longer disease-free survival.
But, at the time, personalized vaccines faced strong headwinds due, largely, to high costs, and commercial interest failed to materialize. “That’s been the major hurdle for a long time,” said Kwak.
Now, however, interest has returned alongside advances in technology and research. The big shift has been the emergence of lower-cost rapid-production mRNA and DNA platforms and a better understanding of how vaccines and potent immune stimulants, like checkpoint inhibitors, can work together to improve outcomes, he explained.
“The timing wasn’t right” back then, Kwak noted. “Now, it’s a different environment and a different time.”
A Turning Point?
Indeed, a decade later, cancer vaccine development appears to be headed in a more promising direction.
Among key cancer vaccines to watch is the mRNA-4157 vaccine, developed by Merck and Moderna, designed to prevent melanoma recurrence. In a recent phase 2 study, patients receiving the mRNA-4157 vaccine alongside pembrolizumab had nearly half the risk for melanoma recurrence or death at 3 years compared with those receiving pembrolizumab alone. Investigators are now evaluating the vaccine in a global phase 3 study in patients with high-risk, stage IIB to IV melanoma following surgery.
Another one to watch is the BNT116 NSCLC vaccine from BioNTech. This vaccine presents the immune system with NSCLC tumor markers to encourage the body to fight cancer cells expressing those markers while ignoring healthy cells. BioNTech also launched a global clinical trial for its vaccine this year.
Other notables include a pancreatic cancer mRNA vaccine, which has shown promising early results in a small trial of 16 patients. Of 16 patients who received the vaccine alongside chemotherapy and after surgery and immunotherapy, 8 responded. Of these eight, six remained recurrence free at 3 years. Investigators noted that the vaccine appeared to stimulate a durable T-cell response in patients who responded.
Kwak has also continued his work on lymphoma vaccines. In August, his team published promising first-in-human data on the use of personalized neoantigen vaccines as an early intervention in untreated patients with lymphoplasmacytic lymphoma. Among nine asymptomatic patients who received the vaccine, all achieved stable disease or better, with no dose-limiting toxicities. One patient had a minor response, and the median time to progression was greater than 72 months.
“The current setting is more for advanced disease,” Kwak explained. “It’s a tougher task, but combined with checkpoint blockade, it may be potent enough to work.”
Still, caution is important. Despite early promise, it’s too soon to tell which, if any, of these investigational vaccines will pan out in the long run. Like investigational drugs, cancer vaccines may show big promising initially but then fail in larger trials.
One key to success, according to Kwak, is to design trials so that even negative results will inform next steps.
But, he noted, failures in large clinical trials will “put a chilling effect on cancer vaccine research again.”
“That’s what keeps me up at night,” he said. “We know the science is fundamentally sound and we have seen glimpses over decades of research that cancer vaccines can work, so it’s really just a matter of tweaking things to optimize trial design.”
Companies tend to design trials to test if a vaccine works or not, without trying to understand why, he said.
“What we need to do is design those so that we can learn from negative results,” he said. That’s what he and his colleagues attempted to do in their recent trial. “We didn’t just look at clinical results; we’re interrogating the actual tumor environment to understand what worked and didn’t and how to tweak that for the next trial.”
Kwak and his colleagues found, for instance, that the vaccine had a greater effect on B cell–derived tumor cells than on cells of plasma origin, so “the most rational design for the next iteration is to combine the vaccine with agents that work directly against plasma cells,” he explained.
As for what’s next, Kwak said: “We’re just focused on trying to do good science and understand. We’ve seen glimpses of success. That’s where we are.”
A version of this article first appeared on Medscape.com.
Vaccines for treating and preventing cancer have long been considered a holy grail in oncology.
But aside from a few notable exceptions — including the human papillomavirus (HPV) vaccine, which has dramatically reduced the incidence of HPV-related cancers, and a Bacillus Calmette-Guerin vaccine, which helps prevent early-stage bladder cancer recurrence — most have failed to deliver.
Following a string of disappointments over the past decade, recent advances in the immunotherapy space are bringing renewed hope for progress.
In an American Association for Cancer Research (AACR) series earlier in 2024, Catherine J. Wu, MD, predicted big strides for cancer vaccines, especially for personalized vaccines that target patient-specific neoantigens — the proteins that form on cancer cells — as well as vaccines that can treat diverse tumor types.
said Wu, the Lavine Family Chair of Preventative Cancer Therapies at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.
A prime example is a personalized, messenger RNA (mRNA)–based vaccine designed to prevent melanoma recurrence. The mRNA-4157 vaccine encodes up to 34 different patient-specific neoantigens.
“This is one of the most exciting developments in modern cancer therapy,” said Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, Coventry, England, who commented on the investigational vaccine via the UK-based Science Media Centre.
Other promising options are on the horizon as well. In August, BioNTech announced a phase 1 global trial to study BNT116 — a vaccine to treat non–small cell lung cancer (NSCLC). BNT116, like mRNA-4157, targets specific antigens in the lung cancer cells.
“This technology is the next big phase of cancer treatment,” Siow Ming Lee, MD, a consultant medical oncologist at University College London Hospitals in England, which is leading the UK trial for the lung cancer and melanoma vaccines, told The Guardian. “We are now entering this very exciting new era of mRNA-based immunotherapy clinical trials to investigate the treatment of lung cancer.”
Still, these predictions have a familiar ring. While the prospects are exciting, delivering on them is another story. There are simply no guarantees these strategies will work as hoped.
Then: Where We Were
Cancer vaccine research began to ramp up in the 2000s, and in 2006, the first-generation HPV vaccine, Gardasil, was approved. Gardasil prevents infection from four strains of HPV that cause about 80% of cervical cancer cases.
In 2010, the Food and Drug Administration approved sipuleucel-T, the first therapeutic cancer vaccine, which improved overall survival in patients with hormone-refractory prostate cancer.
Researchers predicted this approval would “pave the way for developing innovative, next generation of vaccines with enhanced antitumor potency.”
In a 2015 AACR research forecast report, Drew Pardoll, MD, PhD, co-director of the Cancer Immunology and Hematopoiesis Program at Johns Hopkins University, Baltimore, Maryland, said that “we can expect to see encouraging results from studies using cancer vaccines.”
Despite the excitement surrounding cancer vaccines alongside a few successes, the next decade brought a longer string of late-phase disappointments.
In 2016, the phase 3 ACT IV trial of a therapeutic vaccine to treat glioblastoma multiforme (CDX-110) was terminated after it failed to demonstrate improved survival.
In 2017, a phase 3 trial of the therapeutic pancreatic cancer vaccine, GVAX, was stopped early for lack of efficacy.
That year, an attenuated Listeria monocytogenes vaccine to treat pancreatic cancer and mesothelioma also failed to come to fruition. In late 2017, concerns over listeria infections prompted Aduro Biotech to cancel its listeria-based cancer treatment program.
In 2018, a phase 3 trial of belagenpumatucel-L, a therapeutic NSCLC vaccine, failed to demonstrate a significant improvement in survival and further study was discontinued.
And in 2019, a vaccine targeting MAGE-A3, a cancer-testis antigen present in multiple tumor types, failed to meet endpoints for improved survival in a phase 3 trial, leading to discontinuation of the vaccine program.
But these disappointments and failures are normal parts of medical research and drug development and have allowed for incremental advances that helped fuel renewed interest and hope for cancer vaccines, when the timing was right, explained vaccine pioneer Larry W. Kwak, MD, PhD, deputy director of the Comprehensive Cancer Center at City of Hope, Duarte, California.
When it comes to vaccine progress, timing makes a difference. In 2011, Kwak and colleagues published promising phase 3 trial results on a personalized vaccine. The vaccine was a patient-specific tumor-derived antigen for patients with follicular lymphoma in their first remission following chemotherapy. Patients who received the vaccine demonstrated significantly longer disease-free survival.
But, at the time, personalized vaccines faced strong headwinds due, largely, to high costs, and commercial interest failed to materialize. “That’s been the major hurdle for a long time,” said Kwak.
Now, however, interest has returned alongside advances in technology and research. The big shift has been the emergence of lower-cost rapid-production mRNA and DNA platforms and a better understanding of how vaccines and potent immune stimulants, like checkpoint inhibitors, can work together to improve outcomes, he explained.
“The timing wasn’t right” back then, Kwak noted. “Now, it’s a different environment and a different time.”
A Turning Point?
Indeed, a decade later, cancer vaccine development appears to be headed in a more promising direction.
Among key cancer vaccines to watch is the mRNA-4157 vaccine, developed by Merck and Moderna, designed to prevent melanoma recurrence. In a recent phase 2 study, patients receiving the mRNA-4157 vaccine alongside pembrolizumab had nearly half the risk for melanoma recurrence or death at 3 years compared with those receiving pembrolizumab alone. Investigators are now evaluating the vaccine in a global phase 3 study in patients with high-risk, stage IIB to IV melanoma following surgery.
Another one to watch is the BNT116 NSCLC vaccine from BioNTech. This vaccine presents the immune system with NSCLC tumor markers to encourage the body to fight cancer cells expressing those markers while ignoring healthy cells. BioNTech also launched a global clinical trial for its vaccine this year.
Other notables include a pancreatic cancer mRNA vaccine, which has shown promising early results in a small trial of 16 patients. Of 16 patients who received the vaccine alongside chemotherapy and after surgery and immunotherapy, 8 responded. Of these eight, six remained recurrence free at 3 years. Investigators noted that the vaccine appeared to stimulate a durable T-cell response in patients who responded.
Kwak has also continued his work on lymphoma vaccines. In August, his team published promising first-in-human data on the use of personalized neoantigen vaccines as an early intervention in untreated patients with lymphoplasmacytic lymphoma. Among nine asymptomatic patients who received the vaccine, all achieved stable disease or better, with no dose-limiting toxicities. One patient had a minor response, and the median time to progression was greater than 72 months.
“The current setting is more for advanced disease,” Kwak explained. “It’s a tougher task, but combined with checkpoint blockade, it may be potent enough to work.”
Still, caution is important. Despite early promise, it’s too soon to tell which, if any, of these investigational vaccines will pan out in the long run. Like investigational drugs, cancer vaccines may show big promising initially but then fail in larger trials.
One key to success, according to Kwak, is to design trials so that even negative results will inform next steps.
But, he noted, failures in large clinical trials will “put a chilling effect on cancer vaccine research again.”
“That’s what keeps me up at night,” he said. “We know the science is fundamentally sound and we have seen glimpses over decades of research that cancer vaccines can work, so it’s really just a matter of tweaking things to optimize trial design.”
Companies tend to design trials to test if a vaccine works or not, without trying to understand why, he said.
“What we need to do is design those so that we can learn from negative results,” he said. That’s what he and his colleagues attempted to do in their recent trial. “We didn’t just look at clinical results; we’re interrogating the actual tumor environment to understand what worked and didn’t and how to tweak that for the next trial.”
Kwak and his colleagues found, for instance, that the vaccine had a greater effect on B cell–derived tumor cells than on cells of plasma origin, so “the most rational design for the next iteration is to combine the vaccine with agents that work directly against plasma cells,” he explained.
As for what’s next, Kwak said: “We’re just focused on trying to do good science and understand. We’ve seen glimpses of success. That’s where we are.”
A version of this article first appeared on Medscape.com.
Vaccines for treating and preventing cancer have long been considered a holy grail in oncology.
But aside from a few notable exceptions — including the human papillomavirus (HPV) vaccine, which has dramatically reduced the incidence of HPV-related cancers, and a Bacillus Calmette-Guerin vaccine, which helps prevent early-stage bladder cancer recurrence — most have failed to deliver.
Following a string of disappointments over the past decade, recent advances in the immunotherapy space are bringing renewed hope for progress.
In an American Association for Cancer Research (AACR) series earlier in 2024, Catherine J. Wu, MD, predicted big strides for cancer vaccines, especially for personalized vaccines that target patient-specific neoantigens — the proteins that form on cancer cells — as well as vaccines that can treat diverse tumor types.
said Wu, the Lavine Family Chair of Preventative Cancer Therapies at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, both in Boston, Massachusetts.
A prime example is a personalized, messenger RNA (mRNA)–based vaccine designed to prevent melanoma recurrence. The mRNA-4157 vaccine encodes up to 34 different patient-specific neoantigens.
“This is one of the most exciting developments in modern cancer therapy,” said Lawrence Young, a virologist and professor of molecular oncology at the University of Warwick, Coventry, England, who commented on the investigational vaccine via the UK-based Science Media Centre.
Other promising options are on the horizon as well. In August, BioNTech announced a phase 1 global trial to study BNT116 — a vaccine to treat non–small cell lung cancer (NSCLC). BNT116, like mRNA-4157, targets specific antigens in the lung cancer cells.
“This technology is the next big phase of cancer treatment,” Siow Ming Lee, MD, a consultant medical oncologist at University College London Hospitals in England, which is leading the UK trial for the lung cancer and melanoma vaccines, told The Guardian. “We are now entering this very exciting new era of mRNA-based immunotherapy clinical trials to investigate the treatment of lung cancer.”
Still, these predictions have a familiar ring. While the prospects are exciting, delivering on them is another story. There are simply no guarantees these strategies will work as hoped.
Then: Where We Were
Cancer vaccine research began to ramp up in the 2000s, and in 2006, the first-generation HPV vaccine, Gardasil, was approved. Gardasil prevents infection from four strains of HPV that cause about 80% of cervical cancer cases.
In 2010, the Food and Drug Administration approved sipuleucel-T, the first therapeutic cancer vaccine, which improved overall survival in patients with hormone-refractory prostate cancer.
Researchers predicted this approval would “pave the way for developing innovative, next generation of vaccines with enhanced antitumor potency.”
In a 2015 AACR research forecast report, Drew Pardoll, MD, PhD, co-director of the Cancer Immunology and Hematopoiesis Program at Johns Hopkins University, Baltimore, Maryland, said that “we can expect to see encouraging results from studies using cancer vaccines.”
Despite the excitement surrounding cancer vaccines alongside a few successes, the next decade brought a longer string of late-phase disappointments.
In 2016, the phase 3 ACT IV trial of a therapeutic vaccine to treat glioblastoma multiforme (CDX-110) was terminated after it failed to demonstrate improved survival.
In 2017, a phase 3 trial of the therapeutic pancreatic cancer vaccine, GVAX, was stopped early for lack of efficacy.
That year, an attenuated Listeria monocytogenes vaccine to treat pancreatic cancer and mesothelioma also failed to come to fruition. In late 2017, concerns over listeria infections prompted Aduro Biotech to cancel its listeria-based cancer treatment program.
In 2018, a phase 3 trial of belagenpumatucel-L, a therapeutic NSCLC vaccine, failed to demonstrate a significant improvement in survival and further study was discontinued.
And in 2019, a vaccine targeting MAGE-A3, a cancer-testis antigen present in multiple tumor types, failed to meet endpoints for improved survival in a phase 3 trial, leading to discontinuation of the vaccine program.
But these disappointments and failures are normal parts of medical research and drug development and have allowed for incremental advances that helped fuel renewed interest and hope for cancer vaccines, when the timing was right, explained vaccine pioneer Larry W. Kwak, MD, PhD, deputy director of the Comprehensive Cancer Center at City of Hope, Duarte, California.
When it comes to vaccine progress, timing makes a difference. In 2011, Kwak and colleagues published promising phase 3 trial results on a personalized vaccine. The vaccine was a patient-specific tumor-derived antigen for patients with follicular lymphoma in their first remission following chemotherapy. Patients who received the vaccine demonstrated significantly longer disease-free survival.
But, at the time, personalized vaccines faced strong headwinds due, largely, to high costs, and commercial interest failed to materialize. “That’s been the major hurdle for a long time,” said Kwak.
Now, however, interest has returned alongside advances in technology and research. The big shift has been the emergence of lower-cost rapid-production mRNA and DNA platforms and a better understanding of how vaccines and potent immune stimulants, like checkpoint inhibitors, can work together to improve outcomes, he explained.
“The timing wasn’t right” back then, Kwak noted. “Now, it’s a different environment and a different time.”
A Turning Point?
Indeed, a decade later, cancer vaccine development appears to be headed in a more promising direction.
Among key cancer vaccines to watch is the mRNA-4157 vaccine, developed by Merck and Moderna, designed to prevent melanoma recurrence. In a recent phase 2 study, patients receiving the mRNA-4157 vaccine alongside pembrolizumab had nearly half the risk for melanoma recurrence or death at 3 years compared with those receiving pembrolizumab alone. Investigators are now evaluating the vaccine in a global phase 3 study in patients with high-risk, stage IIB to IV melanoma following surgery.
Another one to watch is the BNT116 NSCLC vaccine from BioNTech. This vaccine presents the immune system with NSCLC tumor markers to encourage the body to fight cancer cells expressing those markers while ignoring healthy cells. BioNTech also launched a global clinical trial for its vaccine this year.
Other notables include a pancreatic cancer mRNA vaccine, which has shown promising early results in a small trial of 16 patients. Of 16 patients who received the vaccine alongside chemotherapy and after surgery and immunotherapy, 8 responded. Of these eight, six remained recurrence free at 3 years. Investigators noted that the vaccine appeared to stimulate a durable T-cell response in patients who responded.
Kwak has also continued his work on lymphoma vaccines. In August, his team published promising first-in-human data on the use of personalized neoantigen vaccines as an early intervention in untreated patients with lymphoplasmacytic lymphoma. Among nine asymptomatic patients who received the vaccine, all achieved stable disease or better, with no dose-limiting toxicities. One patient had a minor response, and the median time to progression was greater than 72 months.
“The current setting is more for advanced disease,” Kwak explained. “It’s a tougher task, but combined with checkpoint blockade, it may be potent enough to work.”
Still, caution is important. Despite early promise, it’s too soon to tell which, if any, of these investigational vaccines will pan out in the long run. Like investigational drugs, cancer vaccines may show big promising initially but then fail in larger trials.
One key to success, according to Kwak, is to design trials so that even negative results will inform next steps.
But, he noted, failures in large clinical trials will “put a chilling effect on cancer vaccine research again.”
“That’s what keeps me up at night,” he said. “We know the science is fundamentally sound and we have seen glimpses over decades of research that cancer vaccines can work, so it’s really just a matter of tweaking things to optimize trial design.”
Companies tend to design trials to test if a vaccine works or not, without trying to understand why, he said.
“What we need to do is design those so that we can learn from negative results,” he said. That’s what he and his colleagues attempted to do in their recent trial. “We didn’t just look at clinical results; we’re interrogating the actual tumor environment to understand what worked and didn’t and how to tweak that for the next trial.”
Kwak and his colleagues found, for instance, that the vaccine had a greater effect on B cell–derived tumor cells than on cells of plasma origin, so “the most rational design for the next iteration is to combine the vaccine with agents that work directly against plasma cells,” he explained.
As for what’s next, Kwak said: “We’re just focused on trying to do good science and understand. We’ve seen glimpses of success. That’s where we are.”
A version of this article first appeared on Medscape.com.
FDA Approves Bizengri for NSCLC and Pancreatic Cancers Harboring NRG1 Gene Fusion
Specifically, the systemic agent was approved for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion who progress on or after prior systemic therapy, according to the FDA.
The approval, based on findings from the multicenter, open-label eNRGy study, is the first from the FDA for a systemic therapy in this setting. In the multicohort study, treatment was associated with an overall response rate of 33% and 40% in 64 patients with NSCLC and 40 patients with pancreatic adenocarcinoma, respectively. Median duration of response was 7.4 months in the NSCLC patients and ranged from 3.7 to 16.6 months in those with pancreatic adenocarcinoma.
Adverse reactions occurring in at least 10% of patients included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included increased gamma-glutamyl transferase and decreased hemoglobin, sodium, and platelets.
“The Personalized Medicine Coalition applauds the approval of BIZENGRI®,” Edward Abrahams, president of the Personalized Medicine Coalition, a Washington-based education and advocacy organization, stated in a press release from Merus. “In keeping with the growing number of personalized medicines on the market today, BIZENGRI® offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”
The agent is expected to be available for use in the “coming weeks,” according to Merus.
“The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” noted Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York City, and a principal investigator for the ongoing eNRGy trial. “I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients.”
Prescribing information for zenocutuzumab-zbco includes a Boxed Warning for embryo-fetal toxicity. The recommended treatment dose is 750 mg every 2 weeks until disease progression or unacceptable toxicity.
A version of this article first appeared on Medscape.com.
Specifically, the systemic agent was approved for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion who progress on or after prior systemic therapy, according to the FDA.
The approval, based on findings from the multicenter, open-label eNRGy study, is the first from the FDA for a systemic therapy in this setting. In the multicohort study, treatment was associated with an overall response rate of 33% and 40% in 64 patients with NSCLC and 40 patients with pancreatic adenocarcinoma, respectively. Median duration of response was 7.4 months in the NSCLC patients and ranged from 3.7 to 16.6 months in those with pancreatic adenocarcinoma.
Adverse reactions occurring in at least 10% of patients included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included increased gamma-glutamyl transferase and decreased hemoglobin, sodium, and platelets.
“The Personalized Medicine Coalition applauds the approval of BIZENGRI®,” Edward Abrahams, president of the Personalized Medicine Coalition, a Washington-based education and advocacy organization, stated in a press release from Merus. “In keeping with the growing number of personalized medicines on the market today, BIZENGRI® offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”
The agent is expected to be available for use in the “coming weeks,” according to Merus.
“The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” noted Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York City, and a principal investigator for the ongoing eNRGy trial. “I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients.”
Prescribing information for zenocutuzumab-zbco includes a Boxed Warning for embryo-fetal toxicity. The recommended treatment dose is 750 mg every 2 weeks until disease progression or unacceptable toxicity.
A version of this article first appeared on Medscape.com.
Specifically, the systemic agent was approved for those with advanced, unresectable, or metastatic NSCLC or pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion who progress on or after prior systemic therapy, according to the FDA.
The approval, based on findings from the multicenter, open-label eNRGy study, is the first from the FDA for a systemic therapy in this setting. In the multicohort study, treatment was associated with an overall response rate of 33% and 40% in 64 patients with NSCLC and 40 patients with pancreatic adenocarcinoma, respectively. Median duration of response was 7.4 months in the NSCLC patients and ranged from 3.7 to 16.6 months in those with pancreatic adenocarcinoma.
Adverse reactions occurring in at least 10% of patients included diarrhea, musculoskeletal pain, fatigue, nausea, infusion-related reactions, dyspnea, rash, constipation, vomiting, abdominal pain, and edema. Grade 3 or 4 laboratory abnormalities occurring in at least 10% of patients included increased gamma-glutamyl transferase and decreased hemoglobin, sodium, and platelets.
“The Personalized Medicine Coalition applauds the approval of BIZENGRI®,” Edward Abrahams, president of the Personalized Medicine Coalition, a Washington-based education and advocacy organization, stated in a press release from Merus. “In keeping with the growing number of personalized medicines on the market today, BIZENGRI® offers the only approved NRG1+ therapy for patients with these difficult-to-treat cancers.”
The agent is expected to be available for use in the “coming weeks,” according to Merus.
“The FDA approval of BIZENGRI® marks an important milestone for patients with pancreatic adenocarcinoma or NSCLC that is advanced unresectable or metastatic and harbors the NRG1 gene fusion,” noted Alison Schram, MD, an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, New York City, and a principal investigator for the ongoing eNRGy trial. “I have seen firsthand how treatment with BIZENGRI® can deliver clinically meaningful outcomes for patients.”
Prescribing information for zenocutuzumab-zbco includes a Boxed Warning for embryo-fetal toxicity. The recommended treatment dose is 750 mg every 2 weeks until disease progression or unacceptable toxicity.
A version of this article first appeared on Medscape.com.
Identifying the Best Upfront Regimen for Unresectable CRC Liver Metastasis
A new report demonstrated why patients benefit most from starting on a two-drug chemotherapy regimen — FOLFOX or FOLFIRI — instead of a three-drug regimen — FOLFOXIRI.
The CAIRO5 trial compared overall survival among 294 patients with right sided tumors and/or RAS/BRAF mutations who received FOLFOXIRI (5-fluorouracil [FU], oxaliplatin, irinotecan, plus folinic acid as an enhancer) or investigators’ choice of FOLFOX (5-FU, oxaliplatin, and folinic acid) or FOLFIRI (5-FU, irinotecan, and folinic acid). All patients also received bevacizumab.
In a post hoc analysis, researchers found no overall survival benefit among patients receiving the three-drug regimen. At a median follow-up of just over 5 years, the median overall survival was 23.6 months with FOLFOX or FOLFIRI vs 24.1 months with FOLFOXIRI (P = .44).
The finding means that patients can avoid the extra toxicity associated with combining oxaliplatin and irinotecan without compromising overall survival, Alan P. Venook, MD, a gastrointestinal medical oncologist at the University of California San Francisco, told Medscape Medical News.
The analysis did not stop there in defining the optimal upfront therapy for this patient population.
In a second arm of the analysis, researchers looked at whether swapping in panitumumab for bevacizumab offered any benefit in 236 patients with left-sided tumors and wild-type RAS/BRAF who received either of the two-drug regimens.
Here, the authors also found no benefit of using panitumumab with FOLFOX or FOLFIRI instead of bevacizumab, reporting a median overall survival of 38.3 months with panitumumab vs 39.9 months with bevacizumab.
In addition to avoiding upfront FOLFOXIRI, patients can also avoid the skin reactions and other toxicities associated with panitumumab, including “horrible acne,” Venook said.
Overall, the results support the use of FOLFOX or FOLFIRI with bevacizumab “irrespective of RAS/BRAFV600E status and tumor sidedness” as the initial treatment for CRC with liver-only metastases, concluded the study investigators, from the University Medical Center Utrecht in the Netherlands.
Why Does This Clarity Matter?
The study confirms the standard practice in the United States of starting patients on a two-drug chemotherapy with bevacizumab for the indication and highlights “why we don’t go all in right at the beginning” with a three-drug regimen, Venook said.
In short, more drugs upfront isn’t going to change patients’ long-term survival outcome. Plus, using FOLFOXIRI upfront means “you’ve really pretty much used up all your guns for early treatment,” Venook said.
As for bevacizumab vs panitumumab, most practitioners in the United States favor bevacizumab because of the rash many patients on epidermal growth factor receptor blockers like panitumumab and cetuximab get, Venook said.
Because FOLFOX and FOLFIRI are equally effective on the overall survival front, the decision between them comes down to a balance between patient comorbidities and side effect profiles. Neuropathy, for instance, is more common with FOLFOX, whereas diarrhea is more likely with FOLFIRI, Venook said.
Venook favors FOLFIRI because “almost every patient will develop neuropathy” after seven or eight doses of FOLFOX, which limits its use. “You’re expecting that first treatment to give you the most mileage,” so starting with a treatment “you’re going to get limited use out of ... never made sense to me,” he said.
Venook noted that the results apply only to the older patients studied in CAIRO5 and not necessarily to the ever-growing population of younger people with CRC. Patients in the trial had a median age of 62 years with a performance status of 0-1, a median of 12 liver lesions with no metastases outside the liver, and no contraindications to local or systemic treatment.
The CAIRO5 analysis also looked at what happens after upfront chemotherapy, with the goal being to shrink liver lesions so the lesions can be surgically removed or treated with thermal ablation.
Almost half the patients ultimately underwent resection or ablation, and 39% of those in the FOLFOX or FOLFIRI plus bevacizumab group and 49% in the FOLFOX or FOLFIRI plus panitumumab group then went on to receive adjuvant chemotherapy (ACT) to reduce the risk for recurrence. ACT was recommended in the study, but not required, and consisted of chemotherapy minus bevacizumab or panitumumab.
Overall survival was longest among patients who had complete local treatment without recurrences for at least 6 months (64.3 months) or who had salvage local treatment after early recurrence (58.9 months). Median overall survival was 30.5 months for patients with complete local treatment without salvage after early recurrence, and 28.7 months for patients with incomplete local treatment. Overall survival was worst in patients who remained unresectable (18.3 months).
ACT was associated with improved overall and relapse-free survival, justifying discussing the option with patients who have completed local treatment, the study team said.
CAIRO5 was funded by Roche and Amgen, makers of bevacizumab and panitumumab, respectively. Bond and Venook didn’t have any disclosures.
A version of this article first appeared on Medscape.com.
A new report demonstrated why patients benefit most from starting on a two-drug chemotherapy regimen — FOLFOX or FOLFIRI — instead of a three-drug regimen — FOLFOXIRI.
The CAIRO5 trial compared overall survival among 294 patients with right sided tumors and/or RAS/BRAF mutations who received FOLFOXIRI (5-fluorouracil [FU], oxaliplatin, irinotecan, plus folinic acid as an enhancer) or investigators’ choice of FOLFOX (5-FU, oxaliplatin, and folinic acid) or FOLFIRI (5-FU, irinotecan, and folinic acid). All patients also received bevacizumab.
In a post hoc analysis, researchers found no overall survival benefit among patients receiving the three-drug regimen. At a median follow-up of just over 5 years, the median overall survival was 23.6 months with FOLFOX or FOLFIRI vs 24.1 months with FOLFOXIRI (P = .44).
The finding means that patients can avoid the extra toxicity associated with combining oxaliplatin and irinotecan without compromising overall survival, Alan P. Venook, MD, a gastrointestinal medical oncologist at the University of California San Francisco, told Medscape Medical News.
The analysis did not stop there in defining the optimal upfront therapy for this patient population.
In a second arm of the analysis, researchers looked at whether swapping in panitumumab for bevacizumab offered any benefit in 236 patients with left-sided tumors and wild-type RAS/BRAF who received either of the two-drug regimens.
Here, the authors also found no benefit of using panitumumab with FOLFOX or FOLFIRI instead of bevacizumab, reporting a median overall survival of 38.3 months with panitumumab vs 39.9 months with bevacizumab.
In addition to avoiding upfront FOLFOXIRI, patients can also avoid the skin reactions and other toxicities associated with panitumumab, including “horrible acne,” Venook said.
Overall, the results support the use of FOLFOX or FOLFIRI with bevacizumab “irrespective of RAS/BRAFV600E status and tumor sidedness” as the initial treatment for CRC with liver-only metastases, concluded the study investigators, from the University Medical Center Utrecht in the Netherlands.
Why Does This Clarity Matter?
The study confirms the standard practice in the United States of starting patients on a two-drug chemotherapy with bevacizumab for the indication and highlights “why we don’t go all in right at the beginning” with a three-drug regimen, Venook said.
In short, more drugs upfront isn’t going to change patients’ long-term survival outcome. Plus, using FOLFOXIRI upfront means “you’ve really pretty much used up all your guns for early treatment,” Venook said.
As for bevacizumab vs panitumumab, most practitioners in the United States favor bevacizumab because of the rash many patients on epidermal growth factor receptor blockers like panitumumab and cetuximab get, Venook said.
Because FOLFOX and FOLFIRI are equally effective on the overall survival front, the decision between them comes down to a balance between patient comorbidities and side effect profiles. Neuropathy, for instance, is more common with FOLFOX, whereas diarrhea is more likely with FOLFIRI, Venook said.
Venook favors FOLFIRI because “almost every patient will develop neuropathy” after seven or eight doses of FOLFOX, which limits its use. “You’re expecting that first treatment to give you the most mileage,” so starting with a treatment “you’re going to get limited use out of ... never made sense to me,” he said.
Venook noted that the results apply only to the older patients studied in CAIRO5 and not necessarily to the ever-growing population of younger people with CRC. Patients in the trial had a median age of 62 years with a performance status of 0-1, a median of 12 liver lesions with no metastases outside the liver, and no contraindications to local or systemic treatment.
The CAIRO5 analysis also looked at what happens after upfront chemotherapy, with the goal being to shrink liver lesions so the lesions can be surgically removed or treated with thermal ablation.
Almost half the patients ultimately underwent resection or ablation, and 39% of those in the FOLFOX or FOLFIRI plus bevacizumab group and 49% in the FOLFOX or FOLFIRI plus panitumumab group then went on to receive adjuvant chemotherapy (ACT) to reduce the risk for recurrence. ACT was recommended in the study, but not required, and consisted of chemotherapy minus bevacizumab or panitumumab.
Overall survival was longest among patients who had complete local treatment without recurrences for at least 6 months (64.3 months) or who had salvage local treatment after early recurrence (58.9 months). Median overall survival was 30.5 months for patients with complete local treatment without salvage after early recurrence, and 28.7 months for patients with incomplete local treatment. Overall survival was worst in patients who remained unresectable (18.3 months).
ACT was associated with improved overall and relapse-free survival, justifying discussing the option with patients who have completed local treatment, the study team said.
CAIRO5 was funded by Roche and Amgen, makers of bevacizumab and panitumumab, respectively. Bond and Venook didn’t have any disclosures.
A version of this article first appeared on Medscape.com.
A new report demonstrated why patients benefit most from starting on a two-drug chemotherapy regimen — FOLFOX or FOLFIRI — instead of a three-drug regimen — FOLFOXIRI.
The CAIRO5 trial compared overall survival among 294 patients with right sided tumors and/or RAS/BRAF mutations who received FOLFOXIRI (5-fluorouracil [FU], oxaliplatin, irinotecan, plus folinic acid as an enhancer) or investigators’ choice of FOLFOX (5-FU, oxaliplatin, and folinic acid) or FOLFIRI (5-FU, irinotecan, and folinic acid). All patients also received bevacizumab.
In a post hoc analysis, researchers found no overall survival benefit among patients receiving the three-drug regimen. At a median follow-up of just over 5 years, the median overall survival was 23.6 months with FOLFOX or FOLFIRI vs 24.1 months with FOLFOXIRI (P = .44).
The finding means that patients can avoid the extra toxicity associated with combining oxaliplatin and irinotecan without compromising overall survival, Alan P. Venook, MD, a gastrointestinal medical oncologist at the University of California San Francisco, told Medscape Medical News.
The analysis did not stop there in defining the optimal upfront therapy for this patient population.
In a second arm of the analysis, researchers looked at whether swapping in panitumumab for bevacizumab offered any benefit in 236 patients with left-sided tumors and wild-type RAS/BRAF who received either of the two-drug regimens.
Here, the authors also found no benefit of using panitumumab with FOLFOX or FOLFIRI instead of bevacizumab, reporting a median overall survival of 38.3 months with panitumumab vs 39.9 months with bevacizumab.
In addition to avoiding upfront FOLFOXIRI, patients can also avoid the skin reactions and other toxicities associated with panitumumab, including “horrible acne,” Venook said.
Overall, the results support the use of FOLFOX or FOLFIRI with bevacizumab “irrespective of RAS/BRAFV600E status and tumor sidedness” as the initial treatment for CRC with liver-only metastases, concluded the study investigators, from the University Medical Center Utrecht in the Netherlands.
Why Does This Clarity Matter?
The study confirms the standard practice in the United States of starting patients on a two-drug chemotherapy with bevacizumab for the indication and highlights “why we don’t go all in right at the beginning” with a three-drug regimen, Venook said.
In short, more drugs upfront isn’t going to change patients’ long-term survival outcome. Plus, using FOLFOXIRI upfront means “you’ve really pretty much used up all your guns for early treatment,” Venook said.
As for bevacizumab vs panitumumab, most practitioners in the United States favor bevacizumab because of the rash many patients on epidermal growth factor receptor blockers like panitumumab and cetuximab get, Venook said.
Because FOLFOX and FOLFIRI are equally effective on the overall survival front, the decision between them comes down to a balance between patient comorbidities and side effect profiles. Neuropathy, for instance, is more common with FOLFOX, whereas diarrhea is more likely with FOLFIRI, Venook said.
Venook favors FOLFIRI because “almost every patient will develop neuropathy” after seven or eight doses of FOLFOX, which limits its use. “You’re expecting that first treatment to give you the most mileage,” so starting with a treatment “you’re going to get limited use out of ... never made sense to me,” he said.
Venook noted that the results apply only to the older patients studied in CAIRO5 and not necessarily to the ever-growing population of younger people with CRC. Patients in the trial had a median age of 62 years with a performance status of 0-1, a median of 12 liver lesions with no metastases outside the liver, and no contraindications to local or systemic treatment.
The CAIRO5 analysis also looked at what happens after upfront chemotherapy, with the goal being to shrink liver lesions so the lesions can be surgically removed or treated with thermal ablation.
Almost half the patients ultimately underwent resection or ablation, and 39% of those in the FOLFOX or FOLFIRI plus bevacizumab group and 49% in the FOLFOX or FOLFIRI plus panitumumab group then went on to receive adjuvant chemotherapy (ACT) to reduce the risk for recurrence. ACT was recommended in the study, but not required, and consisted of chemotherapy minus bevacizumab or panitumumab.
Overall survival was longest among patients who had complete local treatment without recurrences for at least 6 months (64.3 months) or who had salvage local treatment after early recurrence (58.9 months). Median overall survival was 30.5 months for patients with complete local treatment without salvage after early recurrence, and 28.7 months for patients with incomplete local treatment. Overall survival was worst in patients who remained unresectable (18.3 months).
ACT was associated with improved overall and relapse-free survival, justifying discussing the option with patients who have completed local treatment, the study team said.
CAIRO5 was funded by Roche and Amgen, makers of bevacizumab and panitumumab, respectively. Bond and Venook didn’t have any disclosures.
A version of this article first appeared on Medscape.com.
FROM JAMA ONCOLOGY
Inside the Patient-Oncologist Bond: Why It’s Often So Strong
Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.
“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”
That was 21 years ago. Today, her current cancer status is “no evidence of disease.”
Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.
In that time,
“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.
Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.
The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.
Gerber isn’t alone in calling out the depth of the oncologist-patient bond.
Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.
“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.
Connecting Through Stress
Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.
Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.
The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.
“I consider my patient’s battles to be my battles,” Khan wrote.
The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.
According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.
The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.
With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”
What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.
“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.
In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.
“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”
A ‘Special Relationship’
Ralph V. Boccia, MD, is often asked what he does.
The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.
“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”
Boccia thinks about one long-term patient who captures this bond.
Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.
Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.
Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.
“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”
Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.
Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.
Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.
More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.
“He has kept me alive,” said Pinson.
The Dying Patient
Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.
After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.
Several months later, Vyas was called for an inpatient consult. It was the same woman.
Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.
The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.
“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”
From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.
For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.
“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.
Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.
Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.
“Doc, I don’t want to die and my kids find me dead. What can we do about it?”
Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.
When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”
But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”
Khan had no relevant disclosures. Boccia and Vyas had no disclosures.
A version of this article appeared on Medscape.com.
Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.
“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”
That was 21 years ago. Today, her current cancer status is “no evidence of disease.”
Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.
In that time,
“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.
Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.
The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.
Gerber isn’t alone in calling out the depth of the oncologist-patient bond.
Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.
“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.
Connecting Through Stress
Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.
Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.
The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.
“I consider my patient’s battles to be my battles,” Khan wrote.
The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.
According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.
The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.
With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”
What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.
“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.
In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.
“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”
A ‘Special Relationship’
Ralph V. Boccia, MD, is often asked what he does.
The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.
“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”
Boccia thinks about one long-term patient who captures this bond.
Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.
Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.
Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.
“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”
Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.
Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.
Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.
More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.
“He has kept me alive,” said Pinson.
The Dying Patient
Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.
After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.
Several months later, Vyas was called for an inpatient consult. It was the same woman.
Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.
The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.
“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”
From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.
For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.
“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.
Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.
Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.
“Doc, I don’t want to die and my kids find me dead. What can we do about it?”
Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.
When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”
But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”
Khan had no relevant disclosures. Boccia and Vyas had no disclosures.
A version of this article appeared on Medscape.com.
Rose Gerber was 39, mother to a third grader and a kindergartener, when the diagnosis came: Advanced HER2-positive breast cancer.
“On one of my first or second appointments, I took in a little picture of Alexander and Isabella,” Gerber said. Gerber showed her oncologist the picture and told her: “I’ll do anything. I just want to be there for them.”
That was 21 years ago. Today, her current cancer status is “no evidence of disease.”
Over the past 2 decades, Gerber has gotten to be there for her children. Her youngest is now a television producer and her oldest, a CPA.
In that time,
“I’ve seen multiple physicians over my 21 years, but my oncologist has always been the focal point, guiding me in the right direction,” Gerber said in an interview.
Over the years, Jaga guided Gerber through a range of treatment decisions, including a Herceptin clinical trial that the mom of two views as lifesaving. Jaga often took on the role of both doctor and therapist, even providing comfort in the smaller moments when Gerber would fret about her weight gain.
The oncologist-patient “bond is very, very, very special,” said Gerber, who now works as director of patient advocacy and education at the Community Oncology Alliance.
Gerber isn’t alone in calling out the depth of the oncologist-patient bond.
Over years, sometimes decades, patients and oncologists can experience a whole world together: The treatment successes, relapses, uncertainties, and tough calls. As a result, a deep therapeutic alliance often develops. And with each new hurdle or decision, that collaborative, human connection between doctor and patient continues to form new layers.
“It’s like a shared bonding experience over trauma, like strangers trapped on a subway and then we get out, and we’re now on the other side, celebrating together,” said Saad Khan, MD, an associate professor of medicine (oncology) at Stanford University in California.
Connecting Through Stress
Although studies exploring the oncologist-patient bond are limited, some research suggests that a strong therapeutic alliance between patients and oncologists not only provides a foundation for quality care but can also help improve patients’ quality of life, protect against suicidal ideation, and increase treatment adherence.
Because of how stressful and frightening a cancer diagnosis can be, creating “a trusting, uninterrupted, almost sacred environment for them” is paramount for Khan. “I have no doubt that the most important part of their treatment is that they find an oncologist in whom they have total confidence,” Khan wrote in a blog.
The stress that patients with cancer experience is well documented, but oncologists take on a lot themselves and can also experience intense stress (.
“I consider my patient’s battles to be my battles,” Khan wrote.
The stress can start with the daily schedule. Oncologists often have a high volume of patients and tend to spend more time with each individual than most.
According to a 2023 survey, oncologists see about 68 patients a week, on average, but some oncologists, like Khan, have many more. Khan typically sees 20-30 patients a day and continues to care for many over years.
The survey also found that oncologists tend to spend a lot of time with their patients. Compared with other physicians, oncologists are two times more likely to spend at least 25 minutes with each patient.
With this kind of patient volume and time, Khan said, “you’re going to be exhausted.”
What can compound the exhaustion are the occasions oncologists need to deliver bad news — this treatment isn’t working, your cancer has come roaring back and, perhaps the hardest, we have no therapeutic options left. The end-of-life conversations, in particular, can be heartbreaking, especially when a patient is young and not ready to stop trying.
“It can be hard for doctors to discuss the end of life,” Don Dizon, MD, director of the Pelvic Malignancies Program at Lifespan Cancer Institute and director of Medical Oncology at Rhode Island Hospital, Providence, wrote in a column in 2023. Instead, it can be tempting and is often easier to focus on the next treatment, “instilling hope that there’s more that can be done,” even if doing more will only do harm.
In the face of these challenging decisions, growing a personal connection with patients over time can help keep oncologists going.
“We’re not just chemotherapy salesmen,” Khan said in an interview. “We get to know their social support network, who’s going to be driving them [to and from appointments], where they go on vacation, their cat’s name, who their neighbors are.”
A ‘Special Relationship’
Ralph V. Boccia, MD, is often asked what he does.
The next question that often comes — “Why do I do what I do?” — is Boccia’s favorite.
“Someone needs to take these patients through their journey,” Boccia, the founder of The Center for Cancer and Blood Disorders, Bethesda, Maryland, typically responds. He also often notes that “it is a special relationship you develop with the patient and their families.”
Boccia thinks about one long-term patient who captures this bond.
Joan Pinson, 70, was diagnosed with multiple myeloma about 25 years ago, when patients’ average survival was about 4 years.
Over a quarter century, Pinson has pivoted to different treatments, amid multiple relapses and remissions. Throughout most of this cancer journey, Boccia has been her primary oncologist, performing a stem cell transplant in 2000 and steering her to six clinical trials.
Her last relapse was 2 years ago, and since then she has been doing well on oral chemotherapy.
“Every time I relapsed, by the next appointment, he’d say, ‘here is what we are going to do,’ ” Pinson recalled. “I never worried, I never panicked. I knew he would take care of me.”
Over the years, Pinson and Boccia have shared many personal moments, sometimes by accident. One special moment happened early on in Pinson’s cancer journey. During an appointment, Boccia had “one ear to the phone” as his wife was about to deliver their first baby, Pinson recalled.
Later, Pinson met that child as a young man working in Boccia’s lab. She has also met Boccia’s wife, a nurse, when she filled in one day in the chemotherapy room.
Boccia now also treats Pinson’s husband who has prostate cancer, and he ruled out cancer when Pinson’s son, now in his 40s, had some worrisome symptoms.
More than 2 decades ago, Pinson told Boccia her goal was to see her youngest child graduate from high school. Now, six grandsons later, she has lived far beyond that goal.
“He has kept me alive,” said Pinson.
The Dying Patient
Harsha Vyas, MD, FACP, remembers the first encounter his office had with a 29-year-old woman referred with a diagnosis of stage IV breast cancer.
After just 15 minutes in the waiting room, the woman announced she was leaving. Although office staff assured the woman that she was next, the patient walked out.
Several months later, Vyas was called for an inpatient consult. It was the same woman.
Her lungs were full of fluid, and she was struggling to breathe, said Vyas, president and CEO of the Cancer Center of Middle Georgia, Dublin, and assistant professor at Augusta University in Georgia.
The woman, a single mother, told Vyas about her three young kids at home and asked him, “Doc, do something, please help me,” he recalled.
“Absolutely,” Vyas told her. But he had to be brutally honest about her prognosis and firm that she needed to follow his instructions. “You have a breast cancer I cannot cure,” he said. “All I can do is control the disease.”
From that first day, until the day she died, she came to every appointment and followed the treatment plan Vyas laid out.
For about 2 years, she responded well to treatment. And as the time passed and the trust grew, she began to open up to him. She showed him pictures. She talked about her children and being a mother.
“I’ve got to get my kids in a better place. I’m going to be there for them,” he recalled her saying.
Vyas admired her resourcefulness. She held down a part-time job, working retail and at a local restaurant. She figured out childcare so she could get to her chemotherapy appointments every 3 weeks and manage the copays.
Several years later, when she knew she was approaching the end of her life, she asked Vyas a question that hit hard.
“Doc, I don’t want to die and my kids find me dead. What can we do about it?”
Vyas, who has three daughters, imagined how traumatic this would be for a child. She and Vyas made the shared decision to cease treatment and begin home hospice. When the end was approaching, a hospice worker took over, waiting for bodily functions to cease.
When news of a death comes, “I say a little prayer, it’s almost like a send-off for that soul. That helps me absorb the news ... and let it go.”
But when the bond grows strong over time, as with his patient with breast cancer, Vyas said, “a piece of her is still with me.”
Khan had no relevant disclosures. Boccia and Vyas had no disclosures.
A version of this article appeared on Medscape.com.
Belly Fat Beats BMI in Predicting Colorectal Cancer Risk
TOPLINE:
METHODOLOGY:
- General obesity, often measured using BMI, is a recognized risk factor for colorectal cancer, but how much of this association is due to central obesity is unclear.
- Researchers assessed the associations between BMI, waist-to-hip ratio (WHR), and waist circumference (WC) with colorectal cancer risk and the degree of independence among these associations in patients aged 40-69 years recruited in the UK Biobank cohort study from 2006 to 2010.
- Anthropometric measurements were performed using standardized methods.
- Cancer registry and hospital data linkage identified colorectal cancer cases in the UK Biobank.
TAKEAWAY:
- Researchers included 460,784 participants (mean age, 56.3 years; 46.7% men), of whom 67.1% had either overweight or obesity, and 49.4% and 60.5% had high or very high WHR and WC, respectively.
- During the median 12.5-year follow-up period, 5977 participants developed colorectal cancer.
- Every SD increase in WHR (hazard ratio [HR], 1.18) showed a stronger association with colorectal cancer risk than in BMI (HR, 1.10).
- After adjustment for BMI, the association between WHR and colorectal cancer risk became slightly attenuated while still staying robust (HR, 1.15); however, after adjusting for WHR, the association between BMI and colorectal cancer risk became substantially weakened (HR, 1.04).
- WHR showed strongly significant associations with colorectal cancer risk across all BMI categories, whereas associations of BMI with colorectal cancer risk were weak and not statistically significant within all WHR categories.
- Central obesity demonstrated consistent associations with both colon and rectal cancer risks in both sexes before and after adjustment for BMI, whereas BMI showed no significant association with colorectal cancer risk in women or with rectal cancer risk after WHR adjustment.
IN PRACTICE:
“[The study] results also underline the importance of integrating additional anthropometric measures such as WHR alongside BMI into routine clinical practice for more effective prevention and management of obesity, whose prevalence is steadily increasing in many countries worldwide, in order to limit the global burden of colorectal cancer and many other obesity-related adverse health outcomes,” the authors wrote.
SOURCE:
The study was led by Fatemeh Safizadeh, German Cancer Research Center (DKFZ), Heidelberg. It was published online in The International Journal of Obesity.
LIMITATIONS:
This study relied on only one-time measurements of anthropometric measures at baseline, without considering previous lifetime history of overweight and obesity or changes during follow-up. Additionally, WHR and WC may not be the most accurate measures of central obesity, as WC includes both visceral and subcutaneous adipose tissue. The study population also showed evidence of healthy volunteer bias, with more health-conscious and socioeconomically advantaged participants being somewhat overrepresented.
DISCLOSURES:
The authors declared no competing interests.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- General obesity, often measured using BMI, is a recognized risk factor for colorectal cancer, but how much of this association is due to central obesity is unclear.
- Researchers assessed the associations between BMI, waist-to-hip ratio (WHR), and waist circumference (WC) with colorectal cancer risk and the degree of independence among these associations in patients aged 40-69 years recruited in the UK Biobank cohort study from 2006 to 2010.
- Anthropometric measurements were performed using standardized methods.
- Cancer registry and hospital data linkage identified colorectal cancer cases in the UK Biobank.
TAKEAWAY:
- Researchers included 460,784 participants (mean age, 56.3 years; 46.7% men), of whom 67.1% had either overweight or obesity, and 49.4% and 60.5% had high or very high WHR and WC, respectively.
- During the median 12.5-year follow-up period, 5977 participants developed colorectal cancer.
- Every SD increase in WHR (hazard ratio [HR], 1.18) showed a stronger association with colorectal cancer risk than in BMI (HR, 1.10).
- After adjustment for BMI, the association between WHR and colorectal cancer risk became slightly attenuated while still staying robust (HR, 1.15); however, after adjusting for WHR, the association between BMI and colorectal cancer risk became substantially weakened (HR, 1.04).
- WHR showed strongly significant associations with colorectal cancer risk across all BMI categories, whereas associations of BMI with colorectal cancer risk were weak and not statistically significant within all WHR categories.
- Central obesity demonstrated consistent associations with both colon and rectal cancer risks in both sexes before and after adjustment for BMI, whereas BMI showed no significant association with colorectal cancer risk in women or with rectal cancer risk after WHR adjustment.
IN PRACTICE:
“[The study] results also underline the importance of integrating additional anthropometric measures such as WHR alongside BMI into routine clinical practice for more effective prevention and management of obesity, whose prevalence is steadily increasing in many countries worldwide, in order to limit the global burden of colorectal cancer and many other obesity-related adverse health outcomes,” the authors wrote.
SOURCE:
The study was led by Fatemeh Safizadeh, German Cancer Research Center (DKFZ), Heidelberg. It was published online in The International Journal of Obesity.
LIMITATIONS:
This study relied on only one-time measurements of anthropometric measures at baseline, without considering previous lifetime history of overweight and obesity or changes during follow-up. Additionally, WHR and WC may not be the most accurate measures of central obesity, as WC includes both visceral and subcutaneous adipose tissue. The study population also showed evidence of healthy volunteer bias, with more health-conscious and socioeconomically advantaged participants being somewhat overrepresented.
DISCLOSURES:
The authors declared no competing interests.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- General obesity, often measured using BMI, is a recognized risk factor for colorectal cancer, but how much of this association is due to central obesity is unclear.
- Researchers assessed the associations between BMI, waist-to-hip ratio (WHR), and waist circumference (WC) with colorectal cancer risk and the degree of independence among these associations in patients aged 40-69 years recruited in the UK Biobank cohort study from 2006 to 2010.
- Anthropometric measurements were performed using standardized methods.
- Cancer registry and hospital data linkage identified colorectal cancer cases in the UK Biobank.
TAKEAWAY:
- Researchers included 460,784 participants (mean age, 56.3 years; 46.7% men), of whom 67.1% had either overweight or obesity, and 49.4% and 60.5% had high or very high WHR and WC, respectively.
- During the median 12.5-year follow-up period, 5977 participants developed colorectal cancer.
- Every SD increase in WHR (hazard ratio [HR], 1.18) showed a stronger association with colorectal cancer risk than in BMI (HR, 1.10).
- After adjustment for BMI, the association between WHR and colorectal cancer risk became slightly attenuated while still staying robust (HR, 1.15); however, after adjusting for WHR, the association between BMI and colorectal cancer risk became substantially weakened (HR, 1.04).
- WHR showed strongly significant associations with colorectal cancer risk across all BMI categories, whereas associations of BMI with colorectal cancer risk were weak and not statistically significant within all WHR categories.
- Central obesity demonstrated consistent associations with both colon and rectal cancer risks in both sexes before and after adjustment for BMI, whereas BMI showed no significant association with colorectal cancer risk in women or with rectal cancer risk after WHR adjustment.
IN PRACTICE:
“[The study] results also underline the importance of integrating additional anthropometric measures such as WHR alongside BMI into routine clinical practice for more effective prevention and management of obesity, whose prevalence is steadily increasing in many countries worldwide, in order to limit the global burden of colorectal cancer and many other obesity-related adverse health outcomes,” the authors wrote.
SOURCE:
The study was led by Fatemeh Safizadeh, German Cancer Research Center (DKFZ), Heidelberg. It was published online in The International Journal of Obesity.
LIMITATIONS:
This study relied on only one-time measurements of anthropometric measures at baseline, without considering previous lifetime history of overweight and obesity or changes during follow-up. Additionally, WHR and WC may not be the most accurate measures of central obesity, as WC includes both visceral and subcutaneous adipose tissue. The study population also showed evidence of healthy volunteer bias, with more health-conscious and socioeconomically advantaged participants being somewhat overrepresented.
DISCLOSURES:
The authors declared no competing interests.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
CRC Screening: Right Patient, Right Test, Right Time
It has been three and a half years since the US Preventive Services Task Force (USPSTF) lowered the age to start colorectal cancer (CRC) screening from 50 to 45. As I mentioned in a previous commentary, two major medical groups — the American Academy of Family Physicians and the American College of Physicians — felt that the evidence was insufficient to support this change.
Comparing CRC screening rates in more than 10 million adults aged 45-49 during the 20 months preceding and 20 months following the USPSTF recommendation, researchers found significant increases during the latter time period, with the greatest increases among persons of high socioeconomic status or living in metropolitan areas.
Another study addressed concerns that younger adults may be less likely to follow up on positive screening results or more likely to have false positives on a fecal immunochemical test (FIT). Patients aged 45-49 years were slightly less likely to have a positive FIT result than 50-year-olds, but they had similar rates of colonoscopy completion and similar percentages of abnormal findings on colonoscopy.
Although the sensitivity and specificity of FIT varies quite a bit across different test brands, its overall effectiveness at reducing colorectal cancer deaths is well established. In 2024, the Food and Drug Administration approved three new screening options: a blood-based screening test (Shield), a next-generation multitarget stool DNA test (Cologuard Plus), and a multitarget stool RNA test (ColoSense) with similar performance characteristics as Cologuard Plus. The latter two tests will become available early next year.
This profusion of noninvasive options for CRC screening will challenge those tasked with developing the next iteration of the USPSTF recommendations. Not only must future guidelines establish what evidence threshold is sufficient to recommend a new screening strategy, but they also will need to consider the population-level consequences of relative utilization of different tests. For example, a cost-effectiveness analysis found that more CRC deaths would occur if people who would have otherwise accepted colonoscopy or fecal tests chose to be screened with Shield instead; however, this negative outcome could be offset if for every three of these test substitutions, two other people chose Shield who would otherwise have not been screened at all.
In the meantime, it is important for primary care clinicians to be familiar with evidence-based intervals for CRC screening tests and test eligibility criteria. A troubling study of patients who completed a multitarget stool DNA test in a Midwestern health system in 2021 found that more than one in five had the test ordered inappropriately, based on USPSTF guidelines. Reasons for inappropriate testing included having had a colonoscopy within the past 10 years, a family history of CRC, symptoms suggestive of possible CRC, age younger than 45, and a prior diagnosis of colonic adenomas.
Just as a medication works best when the patient takes it as prescribed, a CRC screening test is most likely to yield more benefit than harm when it’s provided to the right patient at the right time.
Dr. Lin is Associate Director, Family Medicine Residency Program, at Lancaster General Hospital in Pennsylvania. He reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
It has been three and a half years since the US Preventive Services Task Force (USPSTF) lowered the age to start colorectal cancer (CRC) screening from 50 to 45. As I mentioned in a previous commentary, two major medical groups — the American Academy of Family Physicians and the American College of Physicians — felt that the evidence was insufficient to support this change.
Comparing CRC screening rates in more than 10 million adults aged 45-49 during the 20 months preceding and 20 months following the USPSTF recommendation, researchers found significant increases during the latter time period, with the greatest increases among persons of high socioeconomic status or living in metropolitan areas.
Another study addressed concerns that younger adults may be less likely to follow up on positive screening results or more likely to have false positives on a fecal immunochemical test (FIT). Patients aged 45-49 years were slightly less likely to have a positive FIT result than 50-year-olds, but they had similar rates of colonoscopy completion and similar percentages of abnormal findings on colonoscopy.
Although the sensitivity and specificity of FIT varies quite a bit across different test brands, its overall effectiveness at reducing colorectal cancer deaths is well established. In 2024, the Food and Drug Administration approved three new screening options: a blood-based screening test (Shield), a next-generation multitarget stool DNA test (Cologuard Plus), and a multitarget stool RNA test (ColoSense) with similar performance characteristics as Cologuard Plus. The latter two tests will become available early next year.
This profusion of noninvasive options for CRC screening will challenge those tasked with developing the next iteration of the USPSTF recommendations. Not only must future guidelines establish what evidence threshold is sufficient to recommend a new screening strategy, but they also will need to consider the population-level consequences of relative utilization of different tests. For example, a cost-effectiveness analysis found that more CRC deaths would occur if people who would have otherwise accepted colonoscopy or fecal tests chose to be screened with Shield instead; however, this negative outcome could be offset if for every three of these test substitutions, two other people chose Shield who would otherwise have not been screened at all.
In the meantime, it is important for primary care clinicians to be familiar with evidence-based intervals for CRC screening tests and test eligibility criteria. A troubling study of patients who completed a multitarget stool DNA test in a Midwestern health system in 2021 found that more than one in five had the test ordered inappropriately, based on USPSTF guidelines. Reasons for inappropriate testing included having had a colonoscopy within the past 10 years, a family history of CRC, symptoms suggestive of possible CRC, age younger than 45, and a prior diagnosis of colonic adenomas.
Just as a medication works best when the patient takes it as prescribed, a CRC screening test is most likely to yield more benefit than harm when it’s provided to the right patient at the right time.
Dr. Lin is Associate Director, Family Medicine Residency Program, at Lancaster General Hospital in Pennsylvania. He reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
It has been three and a half years since the US Preventive Services Task Force (USPSTF) lowered the age to start colorectal cancer (CRC) screening from 50 to 45. As I mentioned in a previous commentary, two major medical groups — the American Academy of Family Physicians and the American College of Physicians — felt that the evidence was insufficient to support this change.
Comparing CRC screening rates in more than 10 million adults aged 45-49 during the 20 months preceding and 20 months following the USPSTF recommendation, researchers found significant increases during the latter time period, with the greatest increases among persons of high socioeconomic status or living in metropolitan areas.
Another study addressed concerns that younger adults may be less likely to follow up on positive screening results or more likely to have false positives on a fecal immunochemical test (FIT). Patients aged 45-49 years were slightly less likely to have a positive FIT result than 50-year-olds, but they had similar rates of colonoscopy completion and similar percentages of abnormal findings on colonoscopy.
Although the sensitivity and specificity of FIT varies quite a bit across different test brands, its overall effectiveness at reducing colorectal cancer deaths is well established. In 2024, the Food and Drug Administration approved three new screening options: a blood-based screening test (Shield), a next-generation multitarget stool DNA test (Cologuard Plus), and a multitarget stool RNA test (ColoSense) with similar performance characteristics as Cologuard Plus. The latter two tests will become available early next year.
This profusion of noninvasive options for CRC screening will challenge those tasked with developing the next iteration of the USPSTF recommendations. Not only must future guidelines establish what evidence threshold is sufficient to recommend a new screening strategy, but they also will need to consider the population-level consequences of relative utilization of different tests. For example, a cost-effectiveness analysis found that more CRC deaths would occur if people who would have otherwise accepted colonoscopy or fecal tests chose to be screened with Shield instead; however, this negative outcome could be offset if for every three of these test substitutions, two other people chose Shield who would otherwise have not been screened at all.
In the meantime, it is important for primary care clinicians to be familiar with evidence-based intervals for CRC screening tests and test eligibility criteria. A troubling study of patients who completed a multitarget stool DNA test in a Midwestern health system in 2021 found that more than one in five had the test ordered inappropriately, based on USPSTF guidelines. Reasons for inappropriate testing included having had a colonoscopy within the past 10 years, a family history of CRC, symptoms suggestive of possible CRC, age younger than 45, and a prior diagnosis of colonic adenomas.
Just as a medication works best when the patient takes it as prescribed, a CRC screening test is most likely to yield more benefit than harm when it’s provided to the right patient at the right time.
Dr. Lin is Associate Director, Family Medicine Residency Program, at Lancaster General Hospital in Pennsylvania. He reported no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.