AVAHO

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

An international survey provides new insights into how COVID-19 has affected, and may continue to affect, the field of oncology.

The survey showed that “COVID-19 has had a major impact on the organization of patient care, on the well-being of caregivers, on continued medical education, and on clinical trial activities in oncology,” stated Guy Jerusalem, MD, PhD, of Centre Hospitalier Universitaire de Liège (Belgium).

Dr. Jerusalem presented these findings at the European Society for Medical Oncology Virtual Congress 2020.

The survey was distributed by 20 oncologists from 10 of the countries most affected by COVID-19. Responses were obtained from 109 oncologists representing centers in 18 countries. The responses were recorded between June 17 and July 14, 2020.

The survey consisted of 95 items intended to evaluate the impact of COVID-19 on the organization of oncologic care. Questions encompassed the capacity and service offered at each center, the magnitude of COVID-19–based care interruptions and the reasons for them, the ensuing challenges faced, interventions implemented, and the estimated harms to patients during the pandemic.

The 109 oncologists surveyed had a median of 20 years of oncology experience. A majority of respondents were men (61.5%), and the median age was 48.5 years.

The respondents had worked predominantly (62.4%) at academic hospitals, with 29.6% at community hospitals. Most respondents worked at general hospitals with an oncology unit (66.1%) rather than a specialized separate cancer center (32.1%).

The most common specialty was breast cancer (60.6%), followed by gastrointestinal cancer (10.1%), urogenital cancer (9.2%), and lung cancer (8.3%).
 

Impact on treatment

The treatment modalities affected by the pandemic – through cancellations or delays in more than 10% of patients – included surgery (in 34% of centers), chemotherapy (22%), radiotherapy (13.7%), checkpoint inhibitor therapy (9.1%), monoclonal antibodies (9%), and oral targeted therapy (3.7%).

Among oncologists treating breast cancer, cancellations/delays in more than 10% of patients were reported for everolimus (18%), CDK4/6 inhibitors (8.9%), and endocrine therapy (2.2%).

Overall, 34.8% of respondents reported increased use of granulocyte colony–stimulating factor, and 6.4% reported increased use of erythropoietin.

On the other hand, 11.1% of respondents reported a decrease in the use of double immunotherapy, and 21.9% reported decreased use of corticosteroids.

Not only can the immunosuppressive effects of steroid use increase infection risks, Dr. Jerusalem noted, fever suppression can lead to a delayed diagnosis of COVID-19.

“To circumvent potential higher infection risks or greater disease severity, we use lower doses of steroids, but this is not based on studies,” he said.

“Previous exposure to steroids or being on steroids at the time of COVID-19 infection is a detrimental factor for complications and mortality,” commented ESMO President Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

Frontline Medical News

Dr. Peters noted that the observation was based on lung cancer registry findings. Furthermore, because data from smaller outbreaks of other coronavirus infections suggested worse prognosis and increased mortality, steroid use was already feared in the very early days of the COVID-19 pandemic.

Lastly, earlier cessation of palliative treatment was observed in 32.1% of centers, and 64.2% of respondents agreed that undertreatment because of COVID-19 is a major concern.

Dr. Jerusalem noted that the survey data do not explain the early cessation of palliative treatment. “I suspect that many patients died at home rather than alone in institutions because it was the only way they could die with their families around them.”
 

Telehealth, meetings, and trials

The survey also revealed rationales for the use of teleconsultation, including follow-up (94.5%), oral therapy (92.7%), immunotherapy (57.8%), and chemotherapy (55%).

Most respondents reported more frequent use of virtual meetings for continuing medical education (94%), oncologic team meetings (92%), and tumor boards (82%).

While about 82% of respondents said they were likely to continue the use of telemedicine, 45% said virtual conferences are not an acceptable alternative to live international conferences such as ESMO, Dr. Jerusalem said.

Finally, nearly three-quarters of respondents (72.5%) said all clinical trial activities are or will soon be activated, or never stopped, at their centers. On the other hand, 27.5% of respondents reported that their centers had major protocol violations or deviations, and 37% of respondents said they expect significant reductions in clinical trial activities this year.

Dr. Jerusalem concluded that COVID-19 is having a major, long-term impact on the organization of patient care, caregivers, continued medical education, and clinical trial activities in oncology.

He cautioned that “the risk of a delayed diagnosis of new cancers and economic consequences of COVID-19 on access to health care and cancer treatments have to be carefully evaluated.”

This research was funded by Fondation Léon Fredericq. Dr. Jerusalem disclosed relationships with Novartis, Roche, Lilly, Pfizer, Amgen, Bristol-Myers Squibb, AstraZeneca, Daiichi Sankyo, AbbVie, MedImmune, and Merck. Dr. Peters disclosed relationships with AbbVie, Amgen, AstraZeneca, and many other companies.

SOURCE: Jerusalem G et al. ESMO 2020, Abstract LBA76.

One year into the implementation of the Mission Act, the US Department of Veterans Affairs (VA) continues to expand a wide-ranging third-party-administered program to boost the access of veterans to the civilian medical system, a VA official told colleagues at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO). “VA has given to the third-party administrators what they do well, which is payment of claims, and VA has taken back what we think we can do better—scheduling, care coordination, and customer service,” said Elizabeth Brill, MD, MBA, chief medical officer and senior adviser to the acting assistant undersecretary for Health for Community Care.

            The 2 third-party contractors that run the Community Care Network (CCN) are Optum and TriWest. Both companies now proces patients at all VA medical facilities in the continental US. Optum serves all the states that are entirely (or mainly) in the Central and Eastern Time Zones—except for Texas—plus Puerto Rico, Washington D.C., and the US Virgin Islands. TriWest serves Texas, Hawaii, and the states that are entirely (or mainly) in the Mountain and Pacific Time Zones. The VA has not yet assigned any contractor for Alaska, Guam, American Samoa, and the Northern Mariana Islands.

“We have tried to consolidate as much as possible into the Community Care Network, pulling in a lot of services that were not previously covered, but it’s still not covering 100% of all services that veterans need outside VA medical centers,” said Brill.

Although the VA continues to rely on Veterans Care Agreements, in which health care providers contract directly with the VA, “the main focus of community care is the Community Care Network.” Said Brill. In a pair of regions—encompassing the Midwest, Northeast, and a few other states—90% of private health services are now provided through the network, she said.

One benefit of the new system is a better experience for the health care providers who work with Optum and TriWest. These administrators are responsible for finding providers and providing them with credentials based on appropriate criteria, Brill said. “In prior days, VA paid community providers directly, and some of you may be familiar with the delays that occurred in the system,” she said. “In the new system, we have third-party administrators who pay the providers quickly, and then VA pays them.”

Urgent care services are now available through CCN in most of the continental US and will be expanded to Texas, the Mountain region and the West by the end of September, she said. “We’ve been very pleased to see the response.” Meanwhile, flu shots for enrolled veterans are now available through the system via 60,000 locations.

There are requirements for private health care providers: They must meet new training requirements and submit claims within 180 days. Patients also must meet standards to get community care. For example, patients are eligible for access if the VA can’t serve them within a 30-minute drive time for primary care and mental health care and a 60-minute drive time for specialty care. Similarly, veterans are eligible if they cannot get an appointment within 20 days for primary and mental health care and 28 days for specialty care.

However, Brill insisted, the Mission Act is “not a move toward privatization. Internal VA care is just as important as external VA care,” she said. “This just gives them more choice.”

Brill also noted that there’s more to the Mission Act than expanded access. For example, an expansion of the Program of Comprehensive Assistance for Family Caregivers Program “will start kicking in this fall and the winter,” she said. It will include families of veterans from all eras of service.

The act also is designed to improve infrastructure, although the coronavirus pandemic may disrupt timing, she said. And, she added, it will strengthen the VA’s ability to recruit and keep health care providers through projects like a new scholarship program and more access to medical education debt reduction. 

One year into the implementation of the Mission Act, the US Department of Veterans Affairs (VA) continues to expand a wide-ranging third-party-administered program to boost the access of veterans to the civilian medical system, a VA official told colleagues at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO). “VA has given to the third-party administrators what they do well, which is payment of claims, and VA has taken back what we think we can do better—scheduling, care coordination, and customer service,” said Elizabeth Brill, MD, MBA, chief medical officer and senior adviser to the acting assistant undersecretary for Health for Community Care.

            The 2 third-party contractors that run the Community Care Network (CCN) are Optum and TriWest. Both companies now proces patients at all VA medical facilities in the continental US. Optum serves all the states that are entirely (or mainly) in the Central and Eastern Time Zones—except for Texas—plus Puerto Rico, Washington D.C., and the US Virgin Islands. TriWest serves Texas, Hawaii, and the states that are entirely (or mainly) in the Mountain and Pacific Time Zones. The VA has not yet assigned any contractor for Alaska, Guam, American Samoa, and the Northern Mariana Islands.

“We have tried to consolidate as much as possible into the Community Care Network, pulling in a lot of services that were not previously covered, but it’s still not covering 100% of all services that veterans need outside VA medical centers,” said Brill.

Although the VA continues to rely on Veterans Care Agreements, in which health care providers contract directly with the VA, “the main focus of community care is the Community Care Network.” Said Brill. In a pair of regions—encompassing the Midwest, Northeast, and a few other states—90% of private health services are now provided through the network, she said.

One benefit of the new system is a better experience for the health care providers who work with Optum and TriWest. These administrators are responsible for finding providers and providing them with credentials based on appropriate criteria, Brill said. “In prior days, VA paid community providers directly, and some of you may be familiar with the delays that occurred in the system,” she said. “In the new system, we have third-party administrators who pay the providers quickly, and then VA pays them.”

Urgent care services are now available through CCN in most of the continental US and will be expanded to Texas, the Mountain region and the West by the end of September, she said. “We’ve been very pleased to see the response.” Meanwhile, flu shots for enrolled veterans are now available through the system via 60,000 locations.

There are requirements for private health care providers: They must meet new training requirements and submit claims within 180 days. Patients also must meet standards to get community care. For example, patients are eligible for access if the VA can’t serve them within a 30-minute drive time for primary care and mental health care and a 60-minute drive time for specialty care. Similarly, veterans are eligible if they cannot get an appointment within 20 days for primary and mental health care and 28 days for specialty care.

However, Brill insisted, the Mission Act is “not a move toward privatization. Internal VA care is just as important as external VA care,” she said. “This just gives them more choice.”

Brill also noted that there’s more to the Mission Act than expanded access. For example, an expansion of the Program of Comprehensive Assistance for Family Caregivers Program “will start kicking in this fall and the winter,” she said. It will include families of veterans from all eras of service.

The act also is designed to improve infrastructure, although the coronavirus pandemic may disrupt timing, she said. And, she added, it will strengthen the VA’s ability to recruit and keep health care providers through projects like a new scholarship program and more access to medical education debt reduction. 

One year into the implementation of the Mission Act, the US Department of Veterans Affairs (VA) continues to expand a wide-ranging third-party-administered program to boost the access of veterans to the civilian medical system, a VA official told colleagues at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO). “VA has given to the third-party administrators what they do well, which is payment of claims, and VA has taken back what we think we can do better—scheduling, care coordination, and customer service,” said Elizabeth Brill, MD, MBA, chief medical officer and senior adviser to the acting assistant undersecretary for Health for Community Care.

            The 2 third-party contractors that run the Community Care Network (CCN) are Optum and TriWest. Both companies now proces patients at all VA medical facilities in the continental US. Optum serves all the states that are entirely (or mainly) in the Central and Eastern Time Zones—except for Texas—plus Puerto Rico, Washington D.C., and the US Virgin Islands. TriWest serves Texas, Hawaii, and the states that are entirely (or mainly) in the Mountain and Pacific Time Zones. The VA has not yet assigned any contractor for Alaska, Guam, American Samoa, and the Northern Mariana Islands.

“We have tried to consolidate as much as possible into the Community Care Network, pulling in a lot of services that were not previously covered, but it’s still not covering 100% of all services that veterans need outside VA medical centers,” said Brill.

Although the VA continues to rely on Veterans Care Agreements, in which health care providers contract directly with the VA, “the main focus of community care is the Community Care Network.” Said Brill. In a pair of regions—encompassing the Midwest, Northeast, and a few other states—90% of private health services are now provided through the network, she said.

One benefit of the new system is a better experience for the health care providers who work with Optum and TriWest. These administrators are responsible for finding providers and providing them with credentials based on appropriate criteria, Brill said. “In prior days, VA paid community providers directly, and some of you may be familiar with the delays that occurred in the system,” she said. “In the new system, we have third-party administrators who pay the providers quickly, and then VA pays them.”

Urgent care services are now available through CCN in most of the continental US and will be expanded to Texas, the Mountain region and the West by the end of September, she said. “We’ve been very pleased to see the response.” Meanwhile, flu shots for enrolled veterans are now available through the system via 60,000 locations.

There are requirements for private health care providers: They must meet new training requirements and submit claims within 180 days. Patients also must meet standards to get community care. For example, patients are eligible for access if the VA can’t serve them within a 30-minute drive time for primary care and mental health care and a 60-minute drive time for specialty care. Similarly, veterans are eligible if they cannot get an appointment within 20 days for primary and mental health care and 28 days for specialty care.

However, Brill insisted, the Mission Act is “not a move toward privatization. Internal VA care is just as important as external VA care,” she said. “This just gives them more choice.”

Brill also noted that there’s more to the Mission Act than expanded access. For example, an expansion of the Program of Comprehensive Assistance for Family Caregivers Program “will start kicking in this fall and the winter,” she said. It will include families of veterans from all eras of service.

The act also is designed to improve infrastructure, although the coronavirus pandemic may disrupt timing, she said. And, she added, it will strengthen the VA’s ability to recruit and keep health care providers through projects like a new scholarship program and more access to medical education debt reduction. 

Human papilloma virus (HPV)-mediated squamous cell carcinoma of the head and neck is on the rise, and the lack of herd immunity in young people will ensure growth for many years to come. “We’re really looking at another 30 to 40 years of HPV and oropharynx cancer growth,” said head and neck cancer surgeon Joseph Califano, MD, deputy director of the Moores Cancer Center at the University of California at San Diego, at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO).

            Califano highlighted a 2019 study that estimated the number of diagnoses of oropharynx cancer cases in the US will grow by half to 30,000 by 2030, with the wide majority (about 25,000) in men. In 2016, the annual number of oropharynx cancer cases was 20,124. “The exponential increase in oropharynx cancer incidence in young white US men has ebbed, and modest increases are occurring/anticipated in cohorts born after 1955,” the study authors wrote.

            “Currently in the United States, we don't have adequate vaccine efficiency to provide herd immunity, particularly for young boys,” said Califano. He added that although HPV vaccinations may create herd immunity in 5 to 10 years, the cancers associated with HPV can take decades to develop so a dip in rates won’t come for many years.

            HPV-associated head and neck squamous cell cancer (HNSCC) affects people at a younger age when compared with other head and neck cancers—a decade or 2 earlier, according to Califano. Many patients are nonsmokers and nondrinkers, he said, and tumors may be painless and asymptomatic.

            It’s also becoming clear that the HPV-associated HNSCC can strike across a widespread area of the oropharynx, including the palatine and lingual tonsils, the nasal cavity, nasopharynx, and hypopharynx (the lower part of the voice box), he said. “It has an even larger footprint than we originally supposed when we realized HPV was a dominant mechanism for development of oropharyngeal cancer,” said Califano.

            Describing the extent of these cancers as an “epidemic,” Califono said a turning point in the understanding of HPV’s role in oropharynx cancers came in a “definitive” 2001 study that reported that HPV-positive patients were much more likely to develop oropharynx cancer (adjusted odds ratio, 14.4). Later research found that HPV-associated oropharynx cancers were more common than HPV-associated cervical cancer. Higher lifetime numbers of vaginal sex and oral sex partners are linked to higher risk of HPV-mediated HNSCC, he said, as is prolonged daily marijuana use.

            Califano emphasized the importance of counseling patients about sexual behaviors linked to the cancers, although it’s also important to consider that “the majority of patients don’t have these risk factors.”

            “The diagnosis is not an indication of infidelity or promiscuity,” he added, recalling that he saw at least one marriage dissolve because of “misunderstandings” regarding how the cancer is caused.  

            There are multiple treatment options. Early-stage oropharynx cancers can be treated with primary excision and staging neck dissection or radiotherapy. Multimodality therapy is appropriate for late-stage cancer and can include concurrent chemotherapy and radiation, primary excision, and treatment with concurrent cisplatinum, depending on the case. Also, “patients do really benefit if they’re enrolled in clinical trials.”

The good news is that HPV-positivity is associated with improved survival in oropharynx cancer, he said. He highlighted a 2019 study that said radiotherapy and cisplatin improve survival in HPV-positive oropharynx cancer patients. “This has become the de-facto standard of care for locally advanced, low-risk HPV-positive oropharynx cancer,” he said.

Califano reported no relevant disclosures.

Human papilloma virus (HPV)-mediated squamous cell carcinoma of the head and neck is on the rise, and the lack of herd immunity in young people will ensure growth for many years to come. “We’re really looking at another 30 to 40 years of HPV and oropharynx cancer growth,” said head and neck cancer surgeon Joseph Califano, MD, deputy director of the Moores Cancer Center at the University of California at San Diego, at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO).

            Califano highlighted a 2019 study that estimated the number of diagnoses of oropharynx cancer cases in the US will grow by half to 30,000 by 2030, with the wide majority (about 25,000) in men. In 2016, the annual number of oropharynx cancer cases was 20,124. “The exponential increase in oropharynx cancer incidence in young white US men has ebbed, and modest increases are occurring/anticipated in cohorts born after 1955,” the study authors wrote.

            “Currently in the United States, we don't have adequate vaccine efficiency to provide herd immunity, particularly for young boys,” said Califano. He added that although HPV vaccinations may create herd immunity in 5 to 10 years, the cancers associated with HPV can take decades to develop so a dip in rates won’t come for many years.

            HPV-associated head and neck squamous cell cancer (HNSCC) affects people at a younger age when compared with other head and neck cancers—a decade or 2 earlier, according to Califano. Many patients are nonsmokers and nondrinkers, he said, and tumors may be painless and asymptomatic.

            It’s also becoming clear that the HPV-associated HNSCC can strike across a widespread area of the oropharynx, including the palatine and lingual tonsils, the nasal cavity, nasopharynx, and hypopharynx (the lower part of the voice box), he said. “It has an even larger footprint than we originally supposed when we realized HPV was a dominant mechanism for development of oropharyngeal cancer,” said Califano.

            Describing the extent of these cancers as an “epidemic,” Califono said a turning point in the understanding of HPV’s role in oropharynx cancers came in a “definitive” 2001 study that reported that HPV-positive patients were much more likely to develop oropharynx cancer (adjusted odds ratio, 14.4). Later research found that HPV-associated oropharynx cancers were more common than HPV-associated cervical cancer. Higher lifetime numbers of vaginal sex and oral sex partners are linked to higher risk of HPV-mediated HNSCC, he said, as is prolonged daily marijuana use.

            Califano emphasized the importance of counseling patients about sexual behaviors linked to the cancers, although it’s also important to consider that “the majority of patients don’t have these risk factors.”

            “The diagnosis is not an indication of infidelity or promiscuity,” he added, recalling that he saw at least one marriage dissolve because of “misunderstandings” regarding how the cancer is caused.  

            There are multiple treatment options. Early-stage oropharynx cancers can be treated with primary excision and staging neck dissection or radiotherapy. Multimodality therapy is appropriate for late-stage cancer and can include concurrent chemotherapy and radiation, primary excision, and treatment with concurrent cisplatinum, depending on the case. Also, “patients do really benefit if they’re enrolled in clinical trials.”

The good news is that HPV-positivity is associated with improved survival in oropharynx cancer, he said. He highlighted a 2019 study that said radiotherapy and cisplatin improve survival in HPV-positive oropharynx cancer patients. “This has become the de-facto standard of care for locally advanced, low-risk HPV-positive oropharynx cancer,” he said.

Califano reported no relevant disclosures.

Human papilloma virus (HPV)-mediated squamous cell carcinoma of the head and neck is on the rise, and the lack of herd immunity in young people will ensure growth for many years to come. “We’re really looking at another 30 to 40 years of HPV and oropharynx cancer growth,” said head and neck cancer surgeon Joseph Califano, MD, deputy director of the Moores Cancer Center at the University of California at San Diego, at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO).

            Califano highlighted a 2019 study that estimated the number of diagnoses of oropharynx cancer cases in the US will grow by half to 30,000 by 2030, with the wide majority (about 25,000) in men. In 2016, the annual number of oropharynx cancer cases was 20,124. “The exponential increase in oropharynx cancer incidence in young white US men has ebbed, and modest increases are occurring/anticipated in cohorts born after 1955,” the study authors wrote.

            “Currently in the United States, we don't have adequate vaccine efficiency to provide herd immunity, particularly for young boys,” said Califano. He added that although HPV vaccinations may create herd immunity in 5 to 10 years, the cancers associated with HPV can take decades to develop so a dip in rates won’t come for many years.

            HPV-associated head and neck squamous cell cancer (HNSCC) affects people at a younger age when compared with other head and neck cancers—a decade or 2 earlier, according to Califano. Many patients are nonsmokers and nondrinkers, he said, and tumors may be painless and asymptomatic.

            It’s also becoming clear that the HPV-associated HNSCC can strike across a widespread area of the oropharynx, including the palatine and lingual tonsils, the nasal cavity, nasopharynx, and hypopharynx (the lower part of the voice box), he said. “It has an even larger footprint than we originally supposed when we realized HPV was a dominant mechanism for development of oropharyngeal cancer,” said Califano.

            Describing the extent of these cancers as an “epidemic,” Califono said a turning point in the understanding of HPV’s role in oropharynx cancers came in a “definitive” 2001 study that reported that HPV-positive patients were much more likely to develop oropharynx cancer (adjusted odds ratio, 14.4). Later research found that HPV-associated oropharynx cancers were more common than HPV-associated cervical cancer. Higher lifetime numbers of vaginal sex and oral sex partners are linked to higher risk of HPV-mediated HNSCC, he said, as is prolonged daily marijuana use.

            Califano emphasized the importance of counseling patients about sexual behaviors linked to the cancers, although it’s also important to consider that “the majority of patients don’t have these risk factors.”

            “The diagnosis is not an indication of infidelity or promiscuity,” he added, recalling that he saw at least one marriage dissolve because of “misunderstandings” regarding how the cancer is caused.  

            There are multiple treatment options. Early-stage oropharynx cancers can be treated with primary excision and staging neck dissection or radiotherapy. Multimodality therapy is appropriate for late-stage cancer and can include concurrent chemotherapy and radiation, primary excision, and treatment with concurrent cisplatinum, depending on the case. Also, “patients do really benefit if they’re enrolled in clinical trials.”

The good news is that HPV-positivity is associated with improved survival in oropharynx cancer, he said. He highlighted a 2019 study that said radiotherapy and cisplatin improve survival in HPV-positive oropharynx cancer patients. “This has become the de-facto standard of care for locally advanced, low-risk HPV-positive oropharynx cancer,” he said.

Califano reported no relevant disclosures.

Proton pump inhibitors may short-circuit the benefits of atezolizumab (Tecentriq) in patients with advanced/metastatic urothelial cancer, according to a post hoc analysis of 1,360 subjects from two atezolizumab trials.

Proton pump inhibitor (PPI) use was associated with worse overall and progression-free survival among patients on atezolizumab, but there was no such association in a matched cohort receiving chemotherapy alone. In short, concomitant “PPI users had no atezolizumab benefit,” wrote the investigators led by Ashley Hopkins, PhD, a research fellow at Flinders University in Adelaide, Australia.

This is the first time that PPI use has been shown to be an independent prognostic factor for worse survival in this setting with atezolizumab use – but not with chemotherapy, wrote the authors of the study, published online in Clinical Cancer Research.

“PPIs are overused, or inappropriately used, in patients with cancer by up to 50%, seemingly from a perspective that they will cause no harm. The findings from this study suggest that noncritical PPI use needs to be approached very cautiously, particularly when an immune checkpoint inhibitor is being used to treat urothelial cancer,” Hopkins said in a press release.

Although about one third of cancer patients use PPIs, there has been growing evidence that the changes they induce in the gut microbiome impact immune checkpoint inhibitor (ICI) effectiveness. A similar study of pooled trial data recently found that PPIs, as well as antibiotics, were associated with worse survival in advanced non–small cell lung cancer treated with atezolizumab, while no such tie was found with chemotherapy (Ann Oncol. 2020;31:525-31. doi: 10.1016/j.annonc.2020.01.006).

The mechanism is uncertain. PPIs have been associated with T-cell tolerance, pharmacokinetic changes, and decreased gut microbiota diversity. High diversity, the investigators noted, has been associated with stronger ICI responses in melanoma. Antibiotics have been associated with similar gut dysbiosis.

“It is increasingly evident that altered gut microbiota impacts homeostasis, immune response, cancer prognosis, and ICI efficacy. The hypothetical basis of [our] research is that PPIs are associated with marked changes to the gut microbiota, driven by both altered stomach acidity and direct compound effects, and these changes may impact immunotherapy,” Hopkins said in an email to Medscape.

The associations with urothelial cancer hadn’t been investigated before, so Hopkins and his team pooled patient-level data from the single-arm IMvigor210 trial of atezolizumab for urothelial cancer and the randomized IMvigor211 trial, which pitted atezolizumab against chemotherapy for the indication.

The investigators compared the outcomes of the 471 subjects who were on a PPI from 30 days before to 30 days after starting atezolizumab with the outcomes of 889 subjects who were not on a PPI. Findings were adjusted for tumor histology and the number of prior treatments and metastases sites, as well as age, body mass index, performance status, and other potential confounders.

PPI use was associated with markedly worse overall survival (hazard ratio, 1.52; 95% confidence interval, 1.27-1.83; P < .001) and progression-free survival (HR, 1.38; 95% CI, 1.18-1.62; P < .001) in patients on atezolizumab but not chemotherapy. PPI use was also associated with worse objective response to the ICI (HR, 0.51; 95% CI, 0.32-0.82; P = .006).

In the randomized trial, atezolizumab seemed to offer no overall survival benefit versus chemotherapy when PPIs were onboard (HR, 1.04; 95% CI, 0.81-1.34), but atezolizumab offered a substantial benefit when PPIs were not in use (HR, 0.69; 95% CI, 0.56-0.84). Findings were consistent when limited to the PD-L1 IC2/3 population.

It seems that PPIs negate “the magnitude of atezolizumab efficacy,” the investigators wrote.

Concomitant antibiotics made the effect of PPIs on overall survival with atezolizumab even worse (antibiotics plus PPI: HR 2.51; 95% CI, 1.12-5.59; versus no antibiotics with PPI: HR, 1.44; 95% CI, 1.19-1.74).

The investigators cautioned that, although “the conducted analyses have been adjusted, there is the potential that PPI use constitutes a surrogate marker for an unfit or immunodeficient patient.” They called for further investigation with other ICIs, cancer types, and chemotherapy regimens.

The dose and compliance with PPI therapy were unknown, but the team noted that over 90% of the PPI subjects were on PPIs for long-term reasons, most commonly gastric protection and gastroesophageal reflux disease (GERD). Omeprazole, pantoprazole, and esomeprazole were the most frequently used. 

There were no significant associations between PPI use and the first occurrence of atezolizumab-induced adverse events.

The study was funded by the National Breast Cancer Foundation (Australia) and the Cancer Council South Australia. Hopkins has disclosed no relevant financial relationships. Multiple study authors have financial ties to industry, including makers of ICIs. The full list can be found with the original article.

This article first appeared on Medscape.com.

Proton pump inhibitors may short-circuit the benefits of atezolizumab (Tecentriq) in patients with advanced/metastatic urothelial cancer, according to a post hoc analysis of 1,360 subjects from two atezolizumab trials.

Proton pump inhibitor (PPI) use was associated with worse overall and progression-free survival among patients on atezolizumab, but there was no such association in a matched cohort receiving chemotherapy alone. In short, concomitant “PPI users had no atezolizumab benefit,” wrote the investigators led by Ashley Hopkins, PhD, a research fellow at Flinders University in Adelaide, Australia.

This is the first time that PPI use has been shown to be an independent prognostic factor for worse survival in this setting with atezolizumab use – but not with chemotherapy, wrote the authors of the study, published online in Clinical Cancer Research.

“PPIs are overused, or inappropriately used, in patients with cancer by up to 50%, seemingly from a perspective that they will cause no harm. The findings from this study suggest that noncritical PPI use needs to be approached very cautiously, particularly when an immune checkpoint inhibitor is being used to treat urothelial cancer,” Hopkins said in a press release.

Although about one third of cancer patients use PPIs, there has been growing evidence that the changes they induce in the gut microbiome impact immune checkpoint inhibitor (ICI) effectiveness. A similar study of pooled trial data recently found that PPIs, as well as antibiotics, were associated with worse survival in advanced non–small cell lung cancer treated with atezolizumab, while no such tie was found with chemotherapy (Ann Oncol. 2020;31:525-31. doi: 10.1016/j.annonc.2020.01.006).

The mechanism is uncertain. PPIs have been associated with T-cell tolerance, pharmacokinetic changes, and decreased gut microbiota diversity. High diversity, the investigators noted, has been associated with stronger ICI responses in melanoma. Antibiotics have been associated with similar gut dysbiosis.

“It is increasingly evident that altered gut microbiota impacts homeostasis, immune response, cancer prognosis, and ICI efficacy. The hypothetical basis of [our] research is that PPIs are associated with marked changes to the gut microbiota, driven by both altered stomach acidity and direct compound effects, and these changes may impact immunotherapy,” Hopkins said in an email to Medscape.

The associations with urothelial cancer hadn’t been investigated before, so Hopkins and his team pooled patient-level data from the single-arm IMvigor210 trial of atezolizumab for urothelial cancer and the randomized IMvigor211 trial, which pitted atezolizumab against chemotherapy for the indication.

The investigators compared the outcomes of the 471 subjects who were on a PPI from 30 days before to 30 days after starting atezolizumab with the outcomes of 889 subjects who were not on a PPI. Findings were adjusted for tumor histology and the number of prior treatments and metastases sites, as well as age, body mass index, performance status, and other potential confounders.

PPI use was associated with markedly worse overall survival (hazard ratio, 1.52; 95% confidence interval, 1.27-1.83; P < .001) and progression-free survival (HR, 1.38; 95% CI, 1.18-1.62; P < .001) in patients on atezolizumab but not chemotherapy. PPI use was also associated with worse objective response to the ICI (HR, 0.51; 95% CI, 0.32-0.82; P = .006).

In the randomized trial, atezolizumab seemed to offer no overall survival benefit versus chemotherapy when PPIs were onboard (HR, 1.04; 95% CI, 0.81-1.34), but atezolizumab offered a substantial benefit when PPIs were not in use (HR, 0.69; 95% CI, 0.56-0.84). Findings were consistent when limited to the PD-L1 IC2/3 population.

It seems that PPIs negate “the magnitude of atezolizumab efficacy,” the investigators wrote.

Concomitant antibiotics made the effect of PPIs on overall survival with atezolizumab even worse (antibiotics plus PPI: HR 2.51; 95% CI, 1.12-5.59; versus no antibiotics with PPI: HR, 1.44; 95% CI, 1.19-1.74).

The investigators cautioned that, although “the conducted analyses have been adjusted, there is the potential that PPI use constitutes a surrogate marker for an unfit or immunodeficient patient.” They called for further investigation with other ICIs, cancer types, and chemotherapy regimens.

The dose and compliance with PPI therapy were unknown, but the team noted that over 90% of the PPI subjects were on PPIs for long-term reasons, most commonly gastric protection and gastroesophageal reflux disease (GERD). Omeprazole, pantoprazole, and esomeprazole were the most frequently used. 

There were no significant associations between PPI use and the first occurrence of atezolizumab-induced adverse events.

The study was funded by the National Breast Cancer Foundation (Australia) and the Cancer Council South Australia. Hopkins has disclosed no relevant financial relationships. Multiple study authors have financial ties to industry, including makers of ICIs. The full list can be found with the original article.

This article first appeared on Medscape.com.

Proton pump inhibitors may short-circuit the benefits of atezolizumab (Tecentriq) in patients with advanced/metastatic urothelial cancer, according to a post hoc analysis of 1,360 subjects from two atezolizumab trials.

Proton pump inhibitor (PPI) use was associated with worse overall and progression-free survival among patients on atezolizumab, but there was no such association in a matched cohort receiving chemotherapy alone. In short, concomitant “PPI users had no atezolizumab benefit,” wrote the investigators led by Ashley Hopkins, PhD, a research fellow at Flinders University in Adelaide, Australia.

This is the first time that PPI use has been shown to be an independent prognostic factor for worse survival in this setting with atezolizumab use – but not with chemotherapy, wrote the authors of the study, published online in Clinical Cancer Research.

“PPIs are overused, or inappropriately used, in patients with cancer by up to 50%, seemingly from a perspective that they will cause no harm. The findings from this study suggest that noncritical PPI use needs to be approached very cautiously, particularly when an immune checkpoint inhibitor is being used to treat urothelial cancer,” Hopkins said in a press release.

Although about one third of cancer patients use PPIs, there has been growing evidence that the changes they induce in the gut microbiome impact immune checkpoint inhibitor (ICI) effectiveness. A similar study of pooled trial data recently found that PPIs, as well as antibiotics, were associated with worse survival in advanced non–small cell lung cancer treated with atezolizumab, while no such tie was found with chemotherapy (Ann Oncol. 2020;31:525-31. doi: 10.1016/j.annonc.2020.01.006).

The mechanism is uncertain. PPIs have been associated with T-cell tolerance, pharmacokinetic changes, and decreased gut microbiota diversity. High diversity, the investigators noted, has been associated with stronger ICI responses in melanoma. Antibiotics have been associated with similar gut dysbiosis.

“It is increasingly evident that altered gut microbiota impacts homeostasis, immune response, cancer prognosis, and ICI efficacy. The hypothetical basis of [our] research is that PPIs are associated with marked changes to the gut microbiota, driven by both altered stomach acidity and direct compound effects, and these changes may impact immunotherapy,” Hopkins said in an email to Medscape.

The associations with urothelial cancer hadn’t been investigated before, so Hopkins and his team pooled patient-level data from the single-arm IMvigor210 trial of atezolizumab for urothelial cancer and the randomized IMvigor211 trial, which pitted atezolizumab against chemotherapy for the indication.

The investigators compared the outcomes of the 471 subjects who were on a PPI from 30 days before to 30 days after starting atezolizumab with the outcomes of 889 subjects who were not on a PPI. Findings were adjusted for tumor histology and the number of prior treatments and metastases sites, as well as age, body mass index, performance status, and other potential confounders.

PPI use was associated with markedly worse overall survival (hazard ratio, 1.52; 95% confidence interval, 1.27-1.83; P < .001) and progression-free survival (HR, 1.38; 95% CI, 1.18-1.62; P < .001) in patients on atezolizumab but not chemotherapy. PPI use was also associated with worse objective response to the ICI (HR, 0.51; 95% CI, 0.32-0.82; P = .006).

In the randomized trial, atezolizumab seemed to offer no overall survival benefit versus chemotherapy when PPIs were onboard (HR, 1.04; 95% CI, 0.81-1.34), but atezolizumab offered a substantial benefit when PPIs were not in use (HR, 0.69; 95% CI, 0.56-0.84). Findings were consistent when limited to the PD-L1 IC2/3 population.

It seems that PPIs negate “the magnitude of atezolizumab efficacy,” the investigators wrote.

Concomitant antibiotics made the effect of PPIs on overall survival with atezolizumab even worse (antibiotics plus PPI: HR 2.51; 95% CI, 1.12-5.59; versus no antibiotics with PPI: HR, 1.44; 95% CI, 1.19-1.74).

The investigators cautioned that, although “the conducted analyses have been adjusted, there is the potential that PPI use constitutes a surrogate marker for an unfit or immunodeficient patient.” They called for further investigation with other ICIs, cancer types, and chemotherapy regimens.

The dose and compliance with PPI therapy were unknown, but the team noted that over 90% of the PPI subjects were on PPIs for long-term reasons, most commonly gastric protection and gastroesophageal reflux disease (GERD). Omeprazole, pantoprazole, and esomeprazole were the most frequently used. 

There were no significant associations between PPI use and the first occurrence of atezolizumab-induced adverse events.

The study was funded by the National Breast Cancer Foundation (Australia) and the Cancer Council South Australia. Hopkins has disclosed no relevant financial relationships. Multiple study authors have financial ties to industry, including makers of ICIs. The full list can be found with the original article.

This article first appeared on Medscape.com.

Although COVID-19 has had negative effects on cancer research, the pandemic has also led to democratization of clinical trials, according to a panelist who spoke at the AACR virtual meeting: COVID-19 and Cancer.

The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.

Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.

Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
 

Trial, administrative, and patient-care modifications

COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.

Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.

Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.

Modifications prompted by the pandemic include the following:

• On-site auditing was suspended.
• Oral investigational agents were shipped directly to patients.
• “Remote” informed consent (telephone or video consenting) was permitted.
• Local providers could perform study-related services, with oversight by the research site.
• Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.

“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
 

Operational accomplishments and benefits

The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.

However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.

The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.

Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.

Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.

These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.

Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.

“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.

In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
 

Streamlining trial regulatory processes

In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.

One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.

The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.

Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.

The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
 

Future directions and challenges

The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.

With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.

“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”

Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.

Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.

On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.

The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
 

Shared goals and democratization

The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.

Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.

A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.

Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.

Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.

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

SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.

Although COVID-19 has had negative effects on cancer research, the pandemic has also led to democratization of clinical trials, according to a panelist who spoke at the AACR virtual meeting: COVID-19 and Cancer.

The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.

Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.

Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
 

Trial, administrative, and patient-care modifications

COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.

Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.

Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.

Modifications prompted by the pandemic include the following:

• On-site auditing was suspended.
• Oral investigational agents were shipped directly to patients.
• “Remote” informed consent (telephone or video consenting) was permitted.
• Local providers could perform study-related services, with oversight by the research site.
• Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.

“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
 

Operational accomplishments and benefits

The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.

However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.

The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.

Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.

Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.

These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.

Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.

“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.

In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
 

Streamlining trial regulatory processes

In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.

One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.

The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.

Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.

The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
 

Future directions and challenges

The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.

With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.

“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”

Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.

Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.

On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.

The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
 

Shared goals and democratization

The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.

Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.

A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.

Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.

Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.

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

SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.

Although COVID-19 has had negative effects on cancer research, the pandemic has also led to democratization of clinical trials, according to a panelist who spoke at the AACR virtual meeting: COVID-19 and Cancer.

The pandemic has taught researchers how to decentralize trials, which should not only improve patient satisfaction but increase trial accrual by providing access to typically underserved populations, Patricia M. LoRusso, DO, of Yale University, New Haven, Conn., said at the meeting.

Dr. LoRusso was one of six panelists who participated in a forum about changes to cancer trials that were prompted by the pandemic. The forum was moderated by Keith T. Flaherty, MD, of Massachusetts General Hospital in Boston.

Dr. Flaherty asked the panelists to explain adjustments their organizations have made in response to the pandemic, discuss accomplishments, and speculate on future challenges and priorities.
 

Trial, administrative, and patient-care modifications

COVID-19 put some cancer trials on hold. For others, the pandemic forced sponsors and study chairs to reduce trial complexity and identify nonessential aspects of the studies, according to panelist José Baselga, MD, PhD, of AstraZeneca.

Specifically, exploratory objectives were subjugated to patient safety and a focus on the primary endpoints of each trial.

Once the critical data were identified, study chairs were asked to determine whether data could be obtained through technologies that could substitute for face-to-face contact between patients and staff – for example, patient-reported outcome tools and at-home digital monitoring.

Modifications prompted by the pandemic include the following:

• On-site auditing was suspended.
• Oral investigational agents were shipped directly to patients.
• “Remote” informed consent (telephone or video consenting) was permitted.
• Local providers could perform study-related services, with oversight by the research site.
• Minor deviations from the written protocols were allowed, provided the deviations did not affect patient care or data integrity.

“Obviously, the pandemic has been horrible, but what it has allowed us to do, as investigators in the clinical research landscape, … is to change our focus somewhat and realize, first and foremost, the patient is at the center of this,” Dr. LoRusso said.
 

Operational accomplishments and benefits

The pandemic caused a 40% decline in accrual to studies supported by the National Cancer Institute’s (NCI) Clinical Trials Network (NCTN) from mid-March to early April, according to James H. Doroshow, MD, of NCI.

However, after modifications to administrative and regulatory procedures, accrual to NCTN trials recovered to approximately 80% of prepandemic levels, Dr. Doroshow said.

The pandemic prompted investigators to leverage tools and technology they had not previously used frequently or at all, the panelists pointed out.

Investigators discovered perforce that telehealth could be used for almost all trial-related assessments. In lieu of physical examination, patients could send pictures of rashes and use electronic devices to monitor blood sugar values and vital signs.

Digital radiographic studies were performed at sites that were most convenient for patients, downloaded, and reinterpreted at the study institution. Visiting nurses and neighborhood laboratories enabled less-frequent in-person visits for assessments.

These adjustments have been particularly important for geographically and/or socioeconomically disadvantaged patients, the panelists said.

Overall, there was agreement among the panelists that shared values and trust among regulatory authorities, sponsors, investigators, and clinicians were impressive in their urgency, sincerity, and patient centricity.

“This pandemic … has forced us to think differently and be nimble and creative to our approach to maintaining our overriding goals while at the same time bringing these innovative therapies forward for patients with cancer and other serious and life-threatening diseases as quickly as possible,” said panelist Kristen M. Hege, MD, of Bristol-Myers Squibb.

In fact, Dr. Hege noted, some cancer-related therapies (e.g., BTK inhibitors, JAK inhibitors, and immunomodulatory agents) were “repurposed” rapidly and tested against COVID-related complications.
 

Streamlining trial regulatory processes

In addition to changing ongoing trials, the pandemic has affected how new research projects are launched.

One new study that came together quickly in response to the pandemic is the NCI COVID-19 in Cancer Patients Study (NCCAPS). NCCAPS is a natural history study with biospecimens and an imaging library. It was approved in just 5 weeks and is active in 650 sites, with “gangbusters” accrual, Dr. Doroshow said.

The rapidness of NCCAPS’ design and implementation should prompt the revision of previously accepted timelines for trial activation and lead to streamlined future processes.

Another project that was launched quickly in response to the pandemic is the COVID-19 evidence accelerator, according to Paul G. Kluetz, MD, of the Food and Drug Administration.

The COVID-19 evidence accelerator integrates real-world evidence into a database to provide investigators and health systems with the ability to gather information, design rapid turnaround queries, and share results. The evidence accelerator can provide study chairs with information that may have relevance to the safety of participants in clinical trials.
 

Future directions and challenges

The panelists agreed that pandemic-related modifications in processes will not only accelerate trial approval and activation but should facilitate higher study accrual, increase the diversity of protocol participants, and decrease the costs associated with clinical trial conduct.

With that in mind, the NCI is planning randomized clinical trials in which “process A” is compared with “process B,” Dr. Doroshow said. The goal is to determine which modifications are most likely to make trials available to patients without compromising data integrity or patient safety.

“How much less data do you need to have an outcome that will be similar?” Dr. Doroshow asked. “How many fewer visits, how many fewer tests, how much can you save? Physicians, clinical trialists, all of us respond to data, and if you get the same outcome at a third of the cost, then everybody benefits.”

Nonetheless, we will need to be vigilant for unintended vulnerabilities from well-intended efforts, according to Dr. Kluetz. Study chairs, sponsors, and regulatory agencies will need to be attentive to whether there are important differences in scan quality or interpretation, missing data that influence trial outcomes, and so on.

Dr. Hege pointed out that differences among data sources may be less important when treatments generate large effects but may be vitally important when the relative differences among treatments are small.

On a practical level, decentralizing clinical research may negatively impact the finances of tertiary care centers, which could threaten the required infrastructure for clinical trials, a few panelists noted.

The relative balance of NCI-, industry-, and investigator-initiated trials may require adjustment so that research income is adequate to maintain the costs associated with cancer clinical trials.
 

Shared goals and democratization

The pandemic has required all stakeholders in clinical research to rely on relationships of trust and shared goals, said Caroline Robert, MD, PhD, of Institut Gustave Roussy in Villejuif, France.

Dr. Kluetz summarized those goals as improving trial efficiencies, decreasing patient burden, decentralizing trials, and maintaining trial integrity.

A decentralized clinical trials operational model could lead to better generalizability of study outcomes, normalization of life for patients on studies, and lower costs of trial conduct. As such, decentralization would promote democratization.

Coupled with ongoing efforts to reduce eligibility criteria in cancer trials, the pandemic has brought operational solutions that should be perpetuated and has reminded us of the interlocking and mutually supportive relationships on which clinical research success depends.

Dr. Doroshow and Dr. Kluetz disclosed no conflicts of interest. All other panelists disclosed financial relationships, including employment, with a range of companies.

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

SOURCE: Flaherty KT et al. AACR: COVID-19 and Cancer, Regulatory and Operational Implications of Cancer Clinical Trial Changes During COVID-19.

Abnormal coagulation is a hallmark of COVID-19. Now, as we’re learning more about the high risk of thrombosis, physicians need to prescribe prophylaxis routinely in the hospital, stay alert, and act immediately when signs of trouble appear. “We must have a low suspicion for diagnosis and treatment of thrombosis,” said hematologist-oncologist Thomas DeLoughery, MD, professor of medicine at Oregon Health & Science University in Portland in a presentation at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO).

Still, research is sparse, and there are disagreements about the best strategies to protect patients, said DeLoughery. Physicians recognized coagulation problems early on during the course of the COVID-19 pandemic, he said, and they’re very common. According to DeLoughery, most patients have abnormal coagulation, very high D-dimer test results, and very high fibrinogen levels—even to the extraordinary level of 1,500 mg/dL, he said. And unlike in typical patients with septic shock, patients with thrombosis have a higher risk than bleeding.

A high D-dimer level is a major prognostic indicator of thrombosis and bad outcomes. “It’s representative of widespread coagulation activation, and it can be a sign of pulmonary thrombosis and local thrombosis happening at the site of the COVID infection,” he said.

DeLoughery highlighted an April 2020 study that found that “patients with D‐dimer levels ≥ 2.0 µg/mL had a higher incidence of mortality when compared with those who with D‐dimer levels < 2.0 µg/mL (12/67 vs 1/267; P < .001; hazard ratio, 51.5; 95% CI, 12.9‐206.7).”

Research also suggests that “there's something about getting COVID and going to the intensive care unit (ICU) that dramatically raises the risk of thrombosis,” he said, and the risk goes up over time in the ICU. Venous thrombosis isn’t the only risk. Relatively young patients with COVID have suffered from arterial thrombosis, even though they have minimal to no respiratory symptoms and no cardiovascular risk factors.

As for treatments, DeLoughery noted that thrombosis can occur despite standard prophylaxis, and patients may show resistance to heparin and, therefore, need massive doses. Still, there’s consensus that every patient with COVID-19 in the hospital should get thromboprophylaxis with low-molecular-weight heparin (LMWH), he said, and unfractionated heparin is appropriate for those with renal failure.

“The problem is everything else is controversial,” he said. For example, hematologists are split evenly on whether heparin dosing should be increased beyond standard protocol for patients in the ICU with 1.5 to 3 times normal D-dimers levels. He agreed with this approach but notes that some centers set their D-dimer triggers higher—at 3 to 6 times the normal level.

“The problem is that there’s limited data,” he said. “We have lots of observational studies suggesting benefits from higher doses, but we have no randomized trial data, and the observational studies are not uniform in their recommendations.”

What about outpatient prophylaxis? It appears that risk of thrombosis is < 1% percent when patients are out of the hospital, he said. “This is very reassuring that once the patient gets better, their prothrombotic drive goes away.”

Dr. DeLoughery highlighted the protocol at Oregon Health & Science University:

• Prophylaxis. Everyone with COVID-19 admitted to the hospital receives enoxaparin 40 mg daily. If the patient’s body mass index > 40, it should be increased to twice daily. For patients with renal failure, use unfractionated heparin 5000 u twice daily or enoxaparin 30 mg daily.
• In the ICU. Screen for deep vein thrombosis at admission and every 4 to 5 days thereafter. Increase enoxaparin to 40 mg twice daily, and to 1 mg/kg twice daily if signs of thrombosis develop, such as sudden deterioration, respiratory failure, the patient is too unstable to get a computed tomography, or with D-dimer > 3.0 µg/mL. “People’s thresholds for initiating empiric therapy differ, but this is an option,” he said.

For outpatient patients who are likely to be immobile for a month, 40 mg enoxaparin or 10 mg rivaroxaban are appropriate. “We’re not as aggressive as we used to be about outpatient prophylaxis,” he said.

Moving forward, he said, “this is an area where we really need clinical trials. There's just so much uncertainty.”

DeLoughery reported no disclosures.

Abnormal coagulation is a hallmark of COVID-19. Now, as we’re learning more about the high risk of thrombosis, physicians need to prescribe prophylaxis routinely in the hospital, stay alert, and act immediately when signs of trouble appear. “We must have a low suspicion for diagnosis and treatment of thrombosis,” said hematologist-oncologist Thomas DeLoughery, MD, professor of medicine at Oregon Health & Science University in Portland in a presentation at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO).

Still, research is sparse, and there are disagreements about the best strategies to protect patients, said DeLoughery. Physicians recognized coagulation problems early on during the course of the COVID-19 pandemic, he said, and they’re very common. According to DeLoughery, most patients have abnormal coagulation, very high D-dimer test results, and very high fibrinogen levels—even to the extraordinary level of 1,500 mg/dL, he said. And unlike in typical patients with septic shock, patients with thrombosis have a higher risk than bleeding.

A high D-dimer level is a major prognostic indicator of thrombosis and bad outcomes. “It’s representative of widespread coagulation activation, and it can be a sign of pulmonary thrombosis and local thrombosis happening at the site of the COVID infection,” he said.

DeLoughery highlighted an April 2020 study that found that “patients with D‐dimer levels ≥ 2.0 µg/mL had a higher incidence of mortality when compared with those who with D‐dimer levels < 2.0 µg/mL (12/67 vs 1/267; P < .001; hazard ratio, 51.5; 95% CI, 12.9‐206.7).”

Research also suggests that “there's something about getting COVID and going to the intensive care unit (ICU) that dramatically raises the risk of thrombosis,” he said, and the risk goes up over time in the ICU. Venous thrombosis isn’t the only risk. Relatively young patients with COVID have suffered from arterial thrombosis, even though they have minimal to no respiratory symptoms and no cardiovascular risk factors.

As for treatments, DeLoughery noted that thrombosis can occur despite standard prophylaxis, and patients may show resistance to heparin and, therefore, need massive doses. Still, there’s consensus that every patient with COVID-19 in the hospital should get thromboprophylaxis with low-molecular-weight heparin (LMWH), he said, and unfractionated heparin is appropriate for those with renal failure.

“The problem is everything else is controversial,” he said. For example, hematologists are split evenly on whether heparin dosing should be increased beyond standard protocol for patients in the ICU with 1.5 to 3 times normal D-dimers levels. He agreed with this approach but notes that some centers set their D-dimer triggers higher—at 3 to 6 times the normal level.

“The problem is that there’s limited data,” he said. “We have lots of observational studies suggesting benefits from higher doses, but we have no randomized trial data, and the observational studies are not uniform in their recommendations.”

What about outpatient prophylaxis? It appears that risk of thrombosis is < 1% percent when patients are out of the hospital, he said. “This is very reassuring that once the patient gets better, their prothrombotic drive goes away.”

Dr. DeLoughery highlighted the protocol at Oregon Health & Science University:

• Prophylaxis. Everyone with COVID-19 admitted to the hospital receives enoxaparin 40 mg daily. If the patient’s body mass index > 40, it should be increased to twice daily. For patients with renal failure, use unfractionated heparin 5000 u twice daily or enoxaparin 30 mg daily.
• In the ICU. Screen for deep vein thrombosis at admission and every 4 to 5 days thereafter. Increase enoxaparin to 40 mg twice daily, and to 1 mg/kg twice daily if signs of thrombosis develop, such as sudden deterioration, respiratory failure, the patient is too unstable to get a computed tomography, or with D-dimer > 3.0 µg/mL. “People’s thresholds for initiating empiric therapy differ, but this is an option,” he said.

For outpatient patients who are likely to be immobile for a month, 40 mg enoxaparin or 10 mg rivaroxaban are appropriate. “We’re not as aggressive as we used to be about outpatient prophylaxis,” he said.

Moving forward, he said, “this is an area where we really need clinical trials. There's just so much uncertainty.”

DeLoughery reported no disclosures.

Abnormal coagulation is a hallmark of COVID-19. Now, as we’re learning more about the high risk of thrombosis, physicians need to prescribe prophylaxis routinely in the hospital, stay alert, and act immediately when signs of trouble appear. “We must have a low suspicion for diagnosis and treatment of thrombosis,” said hematologist-oncologist Thomas DeLoughery, MD, professor of medicine at Oregon Health & Science University in Portland in a presentation at the virtual 2020 annual meeting of the Association of VA Hematology/Oncology (AVAHO).

Still, research is sparse, and there are disagreements about the best strategies to protect patients, said DeLoughery. Physicians recognized coagulation problems early on during the course of the COVID-19 pandemic, he said, and they’re very common. According to DeLoughery, most patients have abnormal coagulation, very high D-dimer test results, and very high fibrinogen levels—even to the extraordinary level of 1,500 mg/dL, he said. And unlike in typical patients with septic shock, patients with thrombosis have a higher risk than bleeding.

A high D-dimer level is a major prognostic indicator of thrombosis and bad outcomes. “It’s representative of widespread coagulation activation, and it can be a sign of pulmonary thrombosis and local thrombosis happening at the site of the COVID infection,” he said.

DeLoughery highlighted an April 2020 study that found that “patients with D‐dimer levels ≥ 2.0 µg/mL had a higher incidence of mortality when compared with those who with D‐dimer levels < 2.0 µg/mL (12/67 vs 1/267; P < .001; hazard ratio, 51.5; 95% CI, 12.9‐206.7).”

Research also suggests that “there's something about getting COVID and going to the intensive care unit (ICU) that dramatically raises the risk of thrombosis,” he said, and the risk goes up over time in the ICU. Venous thrombosis isn’t the only risk. Relatively young patients with COVID have suffered from arterial thrombosis, even though they have minimal to no respiratory symptoms and no cardiovascular risk factors.

As for treatments, DeLoughery noted that thrombosis can occur despite standard prophylaxis, and patients may show resistance to heparin and, therefore, need massive doses. Still, there’s consensus that every patient with COVID-19 in the hospital should get thromboprophylaxis with low-molecular-weight heparin (LMWH), he said, and unfractionated heparin is appropriate for those with renal failure.

“The problem is everything else is controversial,” he said. For example, hematologists are split evenly on whether heparin dosing should be increased beyond standard protocol for patients in the ICU with 1.5 to 3 times normal D-dimers levels. He agreed with this approach but notes that some centers set their D-dimer triggers higher—at 3 to 6 times the normal level.

“The problem is that there’s limited data,” he said. “We have lots of observational studies suggesting benefits from higher doses, but we have no randomized trial data, and the observational studies are not uniform in their recommendations.”

What about outpatient prophylaxis? It appears that risk of thrombosis is < 1% percent when patients are out of the hospital, he said. “This is very reassuring that once the patient gets better, their prothrombotic drive goes away.”

Dr. DeLoughery highlighted the protocol at Oregon Health & Science University:

• Prophylaxis. Everyone with COVID-19 admitted to the hospital receives enoxaparin 40 mg daily. If the patient’s body mass index > 40, it should be increased to twice daily. For patients with renal failure, use unfractionated heparin 5000 u twice daily or enoxaparin 30 mg daily.
• In the ICU. Screen for deep vein thrombosis at admission and every 4 to 5 days thereafter. Increase enoxaparin to 40 mg twice daily, and to 1 mg/kg twice daily if signs of thrombosis develop, such as sudden deterioration, respiratory failure, the patient is too unstable to get a computed tomography, or with D-dimer > 3.0 µg/mL. “People’s thresholds for initiating empiric therapy differ, but this is an option,” he said.

For outpatient patients who are likely to be immobile for a month, 40 mg enoxaparin or 10 mg rivaroxaban are appropriate. “We’re not as aggressive as we used to be about outpatient prophylaxis,” he said.

Moving forward, he said, “this is an area where we really need clinical trials. There's just so much uncertainty.”

DeLoughery reported no disclosures.

The US Department of Veterans Affairs (VA) is embracing clinical trials with a focus on oncology, and patients will benefit from new priorities and programs, VA officials reported at the Association of VA Hematology/Oncology (AVAHO) virtual meeting. “The whole model is one that is far more proactive,” said Carolyn Clancy, MD, Under Secretary for Health for Discovery, Education, and Affiliate Networks.

According to Clancy, the department’s top research priority is to increase veteran access to high-quality clinical trials. “Priority number 2 is increasing the real-world impact of VA research,” she said. “Our commitment to veterans and the taxpayers is to reverse and shorten the [research-to-implementation] timeline. And the third priority is to put VA data to work for veterans, not just through people who work in VA and Veterans Health Administration, but through other researchers who can have access to them.”

To meet these goals, VA is engaging in multiple research programs and collaborations. Rachel B. Ramoni, DMD, ScD, the VA chief research and development officer, highlighted a number of the projects in a separate AVAHO meeting presentation, including:

• The National Cancer Institute and VA Interagency Group to Accelerate Trials Enrollment (NAVIGATE), an interagency collaboration between the VA and the National Cancer Institute (NCI). This program established a network of sites to help enrolled veterans take part in NCI-supported clinical trials. “It really got up and running in 2018, and I’m proud to say that over 250 veterans have been enrolled, and enrollment exceeds that at non-NAVIGATE sites,” Ramoni reported. “Clearly, the additional support that these sites are getting is really helping to achieve the outcome of getting more veterans access to these trials.” However, she said, some areas of the nation aren’t yet covered by the program.
• The Precision Oncology Program for Cancer of the Prostate (POPCaP), established through a partnership with the Prostate Cancer Foundation. The foundation provided a $50 million investment. “This program ensures that veterans, no matter where they are, get best-in-class prostate cancer care,” Ramoni explained. “The initial focus was ensuring that men get sequencing if they have metastatic prostate cancer, and that they get access to clinical trials. The really distinguishing factor about POPCaP is that it has built a vibrant community of clinicians, researchers and program offices. The whole is much greater than the sum of its parts.” More POPCaP hubs are in development, she said.
• PATCH (Prostate Cancer Analysis for Therapy Choice), a program funded by the VA and the Prostate Cancer Foundation. “The whole purpose of PATCH is to create this network of sites to systematically go through different clinical trials that are biomarker-driven,” Ramoni said. “One of the great things about PATCH is that it’s leveraging the genetics databases to help proactively identify men who might qualify for these trials and to find them wherever they might be across the system so they have access to these trials.” She also praised the program’s commitment to collaboration and mentorship. “If you’re new to putting together clinical trials concepts or to submitting merit proposals to VA for funding, PATCH is a great place to get into a community that’s supportive and wants to help you succeed.”
• The VA Phenomics Library. This library, based at the Boston VA Medical Center, focuses on improving the analysis of “messy” electronic health record data, Ramoni noted. “There are automated algorithms that go through and help you clean up that data to make sense of it,” she said. “The problem is that it’s really been an every-person-for-himself-or-herself system. Each researcher who needed these phenotypes was creating his or her own.” The Phenomics Library will promote sharing “so there’s not going to be as much wasted time duplicating effort,” she said. “By the end of fiscal year 2021, we will have over 1,000 curated phenotypes in there. We hope that will be a great resource for the oncology community as well as many other communities.”
• Access to Clinical Trials (ACT) for Veterans. “This program, which began a couple of years ago, has really succeeded,” Ramoni said. “We were focusing on decreasing the time it takes to start up multi-site industry trials. When we got started with ACT, it was taking over 200 days to get started. And now, just a couple years later, we are well under 100 days, which is within industry standards.” Also, she said, the VA established a Partnered Research Program office, “which serves to interact with our industry partners and really guide them through the VA system, which can be complex if you’re approaching it for the first time.”

In a separate presentation, Krissa Caroff, MS, CPC, program manager of the Partnered Research Program, said it had quickened the process of implementing clinical trials by tackling roadblocks such as the need for multiple master agreements to be signed. Central coordination has been key, she said, “and we are working closely to ensure that we when have a multisite trial, all the VA sites are utilizing the same single IRB [institutional review board]. We’ve also identified the critical information that we need to collect from industry in order for us to evaluate a trial.”

What’s next? “We really are going to be focusing on oncology trials,” Ramoni insisted. “This is a high priority for us.” She added: “Please share your feedback and experiences with us. And also please communicate amongst your colleagues within your organization to explain how we’re standardizing things within VA.”

The speakers reported no relevant disclosures.  

The US Department of Veterans Affairs (VA) is embracing clinical trials with a focus on oncology, and patients will benefit from new priorities and programs, VA officials reported at the Association of VA Hematology/Oncology (AVAHO) virtual meeting. “The whole model is one that is far more proactive,” said Carolyn Clancy, MD, Under Secretary for Health for Discovery, Education, and Affiliate Networks.

According to Clancy, the department’s top research priority is to increase veteran access to high-quality clinical trials. “Priority number 2 is increasing the real-world impact of VA research,” she said. “Our commitment to veterans and the taxpayers is to reverse and shorten the [research-to-implementation] timeline. And the third priority is to put VA data to work for veterans, not just through people who work in VA and Veterans Health Administration, but through other researchers who can have access to them.”

To meet these goals, VA is engaging in multiple research programs and collaborations. Rachel B. Ramoni, DMD, ScD, the VA chief research and development officer, highlighted a number of the projects in a separate AVAHO meeting presentation, including:

• The National Cancer Institute and VA Interagency Group to Accelerate Trials Enrollment (NAVIGATE), an interagency collaboration between the VA and the National Cancer Institute (NCI). This program established a network of sites to help enrolled veterans take part in NCI-supported clinical trials. “It really got up and running in 2018, and I’m proud to say that over 250 veterans have been enrolled, and enrollment exceeds that at non-NAVIGATE sites,” Ramoni reported. “Clearly, the additional support that these sites are getting is really helping to achieve the outcome of getting more veterans access to these trials.” However, she said, some areas of the nation aren’t yet covered by the program.
• The Precision Oncology Program for Cancer of the Prostate (POPCaP), established through a partnership with the Prostate Cancer Foundation. The foundation provided a $50 million investment. “This program ensures that veterans, no matter where they are, get best-in-class prostate cancer care,” Ramoni explained. “The initial focus was ensuring that men get sequencing if they have metastatic prostate cancer, and that they get access to clinical trials. The really distinguishing factor about POPCaP is that it has built a vibrant community of clinicians, researchers and program offices. The whole is much greater than the sum of its parts.” More POPCaP hubs are in development, she said.
• PATCH (Prostate Cancer Analysis for Therapy Choice), a program funded by the VA and the Prostate Cancer Foundation. “The whole purpose of PATCH is to create this network of sites to systematically go through different clinical trials that are biomarker-driven,” Ramoni said. “One of the great things about PATCH is that it’s leveraging the genetics databases to help proactively identify men who might qualify for these trials and to find them wherever they might be across the system so they have access to these trials.” She also praised the program’s commitment to collaboration and mentorship. “If you’re new to putting together clinical trials concepts or to submitting merit proposals to VA for funding, PATCH is a great place to get into a community that’s supportive and wants to help you succeed.”
• The VA Phenomics Library. This library, based at the Boston VA Medical Center, focuses on improving the analysis of “messy” electronic health record data, Ramoni noted. “There are automated algorithms that go through and help you clean up that data to make sense of it,” she said. “The problem is that it’s really been an every-person-for-himself-or-herself system. Each researcher who needed these phenotypes was creating his or her own.” The Phenomics Library will promote sharing “so there’s not going to be as much wasted time duplicating effort,” she said. “By the end of fiscal year 2021, we will have over 1,000 curated phenotypes in there. We hope that will be a great resource for the oncology community as well as many other communities.”
• Access to Clinical Trials (ACT) for Veterans. “This program, which began a couple of years ago, has really succeeded,” Ramoni said. “We were focusing on decreasing the time it takes to start up multi-site industry trials. When we got started with ACT, it was taking over 200 days to get started. And now, just a couple years later, we are well under 100 days, which is within industry standards.” Also, she said, the VA established a Partnered Research Program office, “which serves to interact with our industry partners and really guide them through the VA system, which can be complex if you’re approaching it for the first time.”

In a separate presentation, Krissa Caroff, MS, CPC, program manager of the Partnered Research Program, said it had quickened the process of implementing clinical trials by tackling roadblocks such as the need for multiple master agreements to be signed. Central coordination has been key, she said, “and we are working closely to ensure that we when have a multisite trial, all the VA sites are utilizing the same single IRB [institutional review board]. We’ve also identified the critical information that we need to collect from industry in order for us to evaluate a trial.”

What’s next? “We really are going to be focusing on oncology trials,” Ramoni insisted. “This is a high priority for us.” She added: “Please share your feedback and experiences with us. And also please communicate amongst your colleagues within your organization to explain how we’re standardizing things within VA.”

The speakers reported no relevant disclosures.  

The US Department of Veterans Affairs (VA) is embracing clinical trials with a focus on oncology, and patients will benefit from new priorities and programs, VA officials reported at the Association of VA Hematology/Oncology (AVAHO) virtual meeting. “The whole model is one that is far more proactive,” said Carolyn Clancy, MD, Under Secretary for Health for Discovery, Education, and Affiliate Networks.

According to Clancy, the department’s top research priority is to increase veteran access to high-quality clinical trials. “Priority number 2 is increasing the real-world impact of VA research,” she said. “Our commitment to veterans and the taxpayers is to reverse and shorten the [research-to-implementation] timeline. And the third priority is to put VA data to work for veterans, not just through people who work in VA and Veterans Health Administration, but through other researchers who can have access to them.”

To meet these goals, VA is engaging in multiple research programs and collaborations. Rachel B. Ramoni, DMD, ScD, the VA chief research and development officer, highlighted a number of the projects in a separate AVAHO meeting presentation, including:

• The National Cancer Institute and VA Interagency Group to Accelerate Trials Enrollment (NAVIGATE), an interagency collaboration between the VA and the National Cancer Institute (NCI). This program established a network of sites to help enrolled veterans take part in NCI-supported clinical trials. “It really got up and running in 2018, and I’m proud to say that over 250 veterans have been enrolled, and enrollment exceeds that at non-NAVIGATE sites,” Ramoni reported. “Clearly, the additional support that these sites are getting is really helping to achieve the outcome of getting more veterans access to these trials.” However, she said, some areas of the nation aren’t yet covered by the program.
• The Precision Oncology Program for Cancer of the Prostate (POPCaP), established through a partnership with the Prostate Cancer Foundation. The foundation provided a $50 million investment. “This program ensures that veterans, no matter where they are, get best-in-class prostate cancer care,” Ramoni explained. “The initial focus was ensuring that men get sequencing if they have metastatic prostate cancer, and that they get access to clinical trials. The really distinguishing factor about POPCaP is that it has built a vibrant community of clinicians, researchers and program offices. The whole is much greater than the sum of its parts.” More POPCaP hubs are in development, she said.
• PATCH (Prostate Cancer Analysis for Therapy Choice), a program funded by the VA and the Prostate Cancer Foundation. “The whole purpose of PATCH is to create this network of sites to systematically go through different clinical trials that are biomarker-driven,” Ramoni said. “One of the great things about PATCH is that it’s leveraging the genetics databases to help proactively identify men who might qualify for these trials and to find them wherever they might be across the system so they have access to these trials.” She also praised the program’s commitment to collaboration and mentorship. “If you’re new to putting together clinical trials concepts or to submitting merit proposals to VA for funding, PATCH is a great place to get into a community that’s supportive and wants to help you succeed.”
• The VA Phenomics Library. This library, based at the Boston VA Medical Center, focuses on improving the analysis of “messy” electronic health record data, Ramoni noted. “There are automated algorithms that go through and help you clean up that data to make sense of it,” she said. “The problem is that it’s really been an every-person-for-himself-or-herself system. Each researcher who needed these phenotypes was creating his or her own.” The Phenomics Library will promote sharing “so there’s not going to be as much wasted time duplicating effort,” she said. “By the end of fiscal year 2021, we will have over 1,000 curated phenotypes in there. We hope that will be a great resource for the oncology community as well as many other communities.”
• Access to Clinical Trials (ACT) for Veterans. “This program, which began a couple of years ago, has really succeeded,” Ramoni said. “We were focusing on decreasing the time it takes to start up multi-site industry trials. When we got started with ACT, it was taking over 200 days to get started. And now, just a couple years later, we are well under 100 days, which is within industry standards.” Also, she said, the VA established a Partnered Research Program office, “which serves to interact with our industry partners and really guide them through the VA system, which can be complex if you’re approaching it for the first time.”

In a separate presentation, Krissa Caroff, MS, CPC, program manager of the Partnered Research Program, said it had quickened the process of implementing clinical trials by tackling roadblocks such as the need for multiple master agreements to be signed. Central coordination has been key, she said, “and we are working closely to ensure that we when have a multisite trial, all the VA sites are utilizing the same single IRB [institutional review board]. We’ve also identified the critical information that we need to collect from industry in order for us to evaluate a trial.”

What’s next? “We really are going to be focusing on oncology trials,” Ramoni insisted. “This is a high priority for us.” She added: “Please share your feedback and experiences with us. And also please communicate amongst your colleagues within your organization to explain how we’re standardizing things within VA.”

The speakers reported no relevant disclosures.  

Click here to access August 2020 Advances in Precision Oncology

Table of Contents

• Foreword
• Introduction: Precision Oncology Changes the Game for VA Health Care
• VA National Precision Oncology Program
• Prostate Cancer Foundation-Department of Veterans Affairs Partnership: A Model to Advance Treatment and Care of Invasive Cancers
• The Precision Oncology Program for Cancer of the Prostate Network: A VA-Prostate Cancer Foundation Alliance
• Leveraging Veterans Health Administration Clinical and Research Resources to Accelerate Discovery and Testing in Precision Oncology
• Strategic Initiatives for Veterans With Lung Cancer
• Integrating Germline Genetics Into Precision Oncology Practice in the Veterans Health Administration: Challenges and Opportunities

Click here to access August 2020 Advances in Precision Oncology

Table of Contents

• Foreword
• Introduction: Precision Oncology Changes the Game for VA Health Care
• VA National Precision Oncology Program
• Prostate Cancer Foundation-Department of Veterans Affairs Partnership: A Model to Advance Treatment and Care of Invasive Cancers
• The Precision Oncology Program for Cancer of the Prostate Network: A VA-Prostate Cancer Foundation Alliance
• Leveraging Veterans Health Administration Clinical and Research Resources to Accelerate Discovery and Testing in Precision Oncology
• Strategic Initiatives for Veterans With Lung Cancer
• Integrating Germline Genetics Into Precision Oncology Practice in the Veterans Health Administration: Challenges and Opportunities

Click here to access August 2020 Advances in Precision Oncology

Table of Contents

• Foreword
• Introduction: Precision Oncology Changes the Game for VA Health Care
• VA National Precision Oncology Program
• Prostate Cancer Foundation-Department of Veterans Affairs Partnership: A Model to Advance Treatment and Care of Invasive Cancers
• The Precision Oncology Program for Cancer of the Prostate Network: A VA-Prostate Cancer Foundation Alliance
• Leveraging Veterans Health Administration Clinical and Research Resources to Accelerate Discovery and Testing in Precision Oncology
• Strategic Initiatives for Veterans With Lung Cancer
• Integrating Germline Genetics Into Precision Oncology Practice in the Veterans Health Administration: Challenges and Opportunities

Statin use was associated with an overall reduction of the risk of death in multiple myeloma (MM) patients, according to a report published in Clinical Lymphoma, Myeloma & Leukemia.

Statins maintained their benefit in patients with multiple myeloma treated with modern-day chemotherapy regimens based on novel agents, but the benefit is less pronounced, reported Amber Afzal, MD, Washington University, St Louis, and colleagues.

Dr. Afzal and colleagues assessed results from 5,922 patients who were diagnosed with multiple myeloma within the study period between 2007 and 2013. The association of statins with mortality in patients with MM was determined using multivariate Cox proportional hazards regression analysis, and a subanalysis was also performed to investigate the effect of statins on mortality in those patients treated with novel agents.
 

Mortality reduction seen

The study found that the use of statins was associated with a 21% reduction in risk of death (adjusted hazard ratio,] 0.79; 95% confidence interval, 0.74-0.84) among all patients with MM. Among the patents treated with novel agents (n = 3,603), statins reduced mortality by 10% (aHR, 0.90; 95% CI, 0.83-0.98).

“Our current study is the first one to support the survival benefit of statins in patients with myeloma treated with modern-day regimens based on novel agents, although it appears the benefit may not be as pronounced. Therefore, as myeloma regimens become more effective, the benefits of statins may diminish,” the researchers concluded.

The authors reported that they had no relevant disclosures.

[email protected]

SOURCE: Afzal A et al. Clin Lymphoma Myeloma Leuk. 2020 Jul 16. doi: 10.1016/j.clml.2020.07.003.

Statin use was associated with an overall reduction of the risk of death in multiple myeloma (MM) patients, according to a report published in Clinical Lymphoma, Myeloma & Leukemia.

Statins maintained their benefit in patients with multiple myeloma treated with modern-day chemotherapy regimens based on novel agents, but the benefit is less pronounced, reported Amber Afzal, MD, Washington University, St Louis, and colleagues.

Dr. Afzal and colleagues assessed results from 5,922 patients who were diagnosed with multiple myeloma within the study period between 2007 and 2013. The association of statins with mortality in patients with MM was determined using multivariate Cox proportional hazards regression analysis, and a subanalysis was also performed to investigate the effect of statins on mortality in those patients treated with novel agents.
 

Mortality reduction seen

The study found that the use of statins was associated with a 21% reduction in risk of death (adjusted hazard ratio,] 0.79; 95% confidence interval, 0.74-0.84) among all patients with MM. Among the patents treated with novel agents (n = 3,603), statins reduced mortality by 10% (aHR, 0.90; 95% CI, 0.83-0.98).

“Our current study is the first one to support the survival benefit of statins in patients with myeloma treated with modern-day regimens based on novel agents, although it appears the benefit may not be as pronounced. Therefore, as myeloma regimens become more effective, the benefits of statins may diminish,” the researchers concluded.

The authors reported that they had no relevant disclosures.

[email protected]

SOURCE: Afzal A et al. Clin Lymphoma Myeloma Leuk. 2020 Jul 16. doi: 10.1016/j.clml.2020.07.003.

Statin use was associated with an overall reduction of the risk of death in multiple myeloma (MM) patients, according to a report published in Clinical Lymphoma, Myeloma & Leukemia.

Statins maintained their benefit in patients with multiple myeloma treated with modern-day chemotherapy regimens based on novel agents, but the benefit is less pronounced, reported Amber Afzal, MD, Washington University, St Louis, and colleagues.

Dr. Afzal and colleagues assessed results from 5,922 patients who were diagnosed with multiple myeloma within the study period between 2007 and 2013. The association of statins with mortality in patients with MM was determined using multivariate Cox proportional hazards regression analysis, and a subanalysis was also performed to investigate the effect of statins on mortality in those patients treated with novel agents.
 

Mortality reduction seen

The study found that the use of statins was associated with a 21% reduction in risk of death (adjusted hazard ratio,] 0.79; 95% confidence interval, 0.74-0.84) among all patients with MM. Among the patents treated with novel agents (n = 3,603), statins reduced mortality by 10% (aHR, 0.90; 95% CI, 0.83-0.98).

“Our current study is the first one to support the survival benefit of statins in patients with myeloma treated with modern-day regimens based on novel agents, although it appears the benefit may not be as pronounced. Therefore, as myeloma regimens become more effective, the benefits of statins may diminish,” the researchers concluded.

The authors reported that they had no relevant disclosures.

[email protected]

SOURCE: Afzal A et al. Clin Lymphoma Myeloma Leuk. 2020 Jul 16. doi: 10.1016/j.clml.2020.07.003.