Head & Neck/Thyroid Cancers

Two months after the first patient with COVID-19 was identified in China, the first case was reported in the United States in the Seattle, Washington, metropolitan area.

Seattle rapidly became the first US epicenter for COVID-19, and local experts are now offering their expertise and advice on how to provide optimal cancer care during the pandemic in a special feature published online March 20 in the Journal of the National Comprehensive Cancer Network.

“We began implementing measures in early March, including infection control and screening of visitors, staff, and patients at the door,” said lead author Masumi Ueda, MD, who holds positions at the Seattle Cancer Care Alliance, the University of Washington, and the Fred Hutchinson Research Center.

“A lot of changes have been implemented, and it changes on a daily basis. We are responding to the growing rate of COVID-19 infection in the community,” she told Medscape Medical News.

Ueda notes that as a result of the quick implementation of new procedures, so far, very few cancer patients at their facilities have been infected by the virus. “It has not hit our cancer population hard, which is a good thing,” she said.

Create “Incident Command Structure”

In sharing their experience, the authors emphasize the importance of keeping channels of communication open between all stakeholders ― administrators and staff, patients, caregivers, and the general public. They also recommend that each facility create an “incident command structure” that can provide early coordination of institution-wide efforts and that can rapidly respond to changing information.

Ueda noted that their command structure was set up very early on, “so we could get communication set up and start building an infrastructure for response.”

Several areas of care that required new strategies were addressed, both to protect patients and to work around staff shortages caused by possible exposure and/or school closings, as well as projected shortages of supplies and hospital resources.

First and foremost was to identify patients and visitors who had respiratory symptoms and to provide them with masks. Although this is always routine practice during the respiratory virus season, screening has now been initiated at entry points throughout the system.

“We were lucky in Seattle and Washington state in that the University of Washington virology lab developed PCR [polymerase chain reaction] testing early on for COVID-19, which subsequently got FDA approval,” said Ueda. “So we were able to have local testing and didn’t have to rely on the state lab. Testing has also been rapidly scaled up.”

Initiating a comprehensive policy for testing staff, tracking results and exposures for persons under investigation, and defining when it is possible to return to work are essential elements for maintaining a stable workforce. In addition, reinforcing a strict “stay at home when ill” policy and providing access to testing for symptomatic staff have been key to limiting exposures.

“What is unique to our region is that we had testing early on, and we are turning it around in 24 hours,” she pointed out. “This is important for staff to be able to return to work.” Currently, staff, patients, and visitors are being tested only if they show the cardinal symptoms associated with COVID-19: fever, shortness of breath, and cough, although muscle aches have recently been added to their testing protocol.

“I think if we had unlimited capacity, we might consider testing people who are asymptomatic,” Ueda noted, “although if you don’t have symptoms, you may not have the viral load needed for an accurate test.”

Educational materials explaining infection control were also needed for patients and families, along with signs and a website to provide COVID-19 education. These were quickly developed.

In addition, a telephone triage line was established for patients with mild symptoms in order to minimize exposures in clinics and to lessen the number of patients presenting at emergency departments.

Outpatient Care

Because theirs is a referral center, many cancer patients come from out of town, and so there is concern about exposing nonlocal patients to COVID-19 as the virus spreads in the Seattle area. In addition, staffing shortages due to factors such as illness, exposure, and school closures are anticipated.

To address these problems, an initial priority was to establish a “multilayer” coverage system for the clinics in the event that practitioners had to be quarantined on short notice, the authors explain.

One decision was to reschedule all wellness visits for current patients or to use telemedicine. Capacity for that option expanded quickly, which was greatly helped by the recent decision by the Centers for Medicare & Medicaid Services to lift Medicare restrictions on the use of certain telemedicine services.

Another approach is to defer all consultations for second opinions for patients who were already undergoing treatment and to increase clinic hours of operations and capabilities for acute evaluations. This helps reserve emergency departments and hospital resources for patients who require higher-level care, the authors comment.

Treatment Decisions

Treatment decisions were more challenging to make, the authors note. One decision was that, despite the risk for COVID-19 for patients with solid tumors, adjuvant therapy with curative intent should proceed, they note. Similarly, patients with metastatic disease might lose the window of opportunity for treatment if it is delayed.

Treatment for aggressive hematologic malignancies is usually urgent, and stem cell transplant and cellular immunotherapies that provide curative treatments cannot be delayed in many cases.

Enrollment in clinical trials will most likely be limited to those trials that are most likely to benefit the patient.

Ueda noted that, because their patients come from all over the country, they are now conducting consultations for stem cell transplant by telephone so that nonlocal patients do not have to travel to Seattle. “If there is some way we can delay the treatment, we have taken that approach,” Ueda told Medscape Medical News. “If we can divert a patient to an area that is not as heavily affected, that’s another option we are taking.”

Although cancer surgery is not considered elective, surgical intervention needs to be prioritized, the authors comment. In the Seattle system, there is currently a 2-week ban on elective surgery in the healthcare system, owing to limited availability of personal protective equipment (PPE), staffing, and beds.

The oncology teams are currently reviewing treatment regimens to determine which treatments might lessen immunosuppression and which treatment options can be moved from the inpatient to the outpatient setting or can be delayed.

Inpatient Care

For hospitalized patients, several issues are being addressed. The priority is to prepare for an upcoming shortage of beds and resources because of the surge of patients with COVID-19 that is predicted. For both clinic and hospitalized patients, shortages of blood products have necessitated stricter adherence to thresholds for transfusion, and consideration is being given to lowering those thresholds.

Another important problem is the need to conserve PPE, which includes masks, gowns, gloves, and other products. The Seattle teams have implemented solutions such as favoring handwashing with soap and water over the use of hand gel for standard-precaution rooms, limiting the number of personnel entering patient rooms (so as to use less PPE), and reducing nursing procedures that require PPE, such as measuring urine output, unless they are necessary.

In addition, a no-visitor policy has been adopted in inpatient units to conserve PPE, with the exception of end-of-life situations.

The Future

The future trajectory of the COVID-19 pandemic is uncertain, Ueda commented. She emphasized that “we must continue to prepare for its widespread impact. The unknown is what we are looking at. We are expecting it to evolve, and the number of infections cannot go down.”

Ueda and coauthors end their article on a positive note. “To many of us, this has become the health care challenge of our generation, one that modern cancer therapy has never had to face. We will prevail, and when the pandemic ends, we will all be proud of what we did for our patients and each other in this critical moment for humanity.”

Two months after the first patient with COVID-19 was identified in China, the first case was reported in the United States in the Seattle, Washington, metropolitan area.

Seattle rapidly became the first US epicenter for COVID-19, and local experts are now offering their expertise and advice on how to provide optimal cancer care during the pandemic in a special feature published online March 20 in the Journal of the National Comprehensive Cancer Network.

“We began implementing measures in early March, including infection control and screening of visitors, staff, and patients at the door,” said lead author Masumi Ueda, MD, who holds positions at the Seattle Cancer Care Alliance, the University of Washington, and the Fred Hutchinson Research Center.

“A lot of changes have been implemented, and it changes on a daily basis. We are responding to the growing rate of COVID-19 infection in the community,” she told Medscape Medical News.

Ueda notes that as a result of the quick implementation of new procedures, so far, very few cancer patients at their facilities have been infected by the virus. “It has not hit our cancer population hard, which is a good thing,” she said.

Create “Incident Command Structure”

In sharing their experience, the authors emphasize the importance of keeping channels of communication open between all stakeholders ― administrators and staff, patients, caregivers, and the general public. They also recommend that each facility create an “incident command structure” that can provide early coordination of institution-wide efforts and that can rapidly respond to changing information.

Ueda noted that their command structure was set up very early on, “so we could get communication set up and start building an infrastructure for response.”

Several areas of care that required new strategies were addressed, both to protect patients and to work around staff shortages caused by possible exposure and/or school closings, as well as projected shortages of supplies and hospital resources.

First and foremost was to identify patients and visitors who had respiratory symptoms and to provide them with masks. Although this is always routine practice during the respiratory virus season, screening has now been initiated at entry points throughout the system.

“We were lucky in Seattle and Washington state in that the University of Washington virology lab developed PCR [polymerase chain reaction] testing early on for COVID-19, which subsequently got FDA approval,” said Ueda. “So we were able to have local testing and didn’t have to rely on the state lab. Testing has also been rapidly scaled up.”

Initiating a comprehensive policy for testing staff, tracking results and exposures for persons under investigation, and defining when it is possible to return to work are essential elements for maintaining a stable workforce. In addition, reinforcing a strict “stay at home when ill” policy and providing access to testing for symptomatic staff have been key to limiting exposures.

“What is unique to our region is that we had testing early on, and we are turning it around in 24 hours,” she pointed out. “This is important for staff to be able to return to work.” Currently, staff, patients, and visitors are being tested only if they show the cardinal symptoms associated with COVID-19: fever, shortness of breath, and cough, although muscle aches have recently been added to their testing protocol.

“I think if we had unlimited capacity, we might consider testing people who are asymptomatic,” Ueda noted, “although if you don’t have symptoms, you may not have the viral load needed for an accurate test.”

Educational materials explaining infection control were also needed for patients and families, along with signs and a website to provide COVID-19 education. These were quickly developed.

In addition, a telephone triage line was established for patients with mild symptoms in order to minimize exposures in clinics and to lessen the number of patients presenting at emergency departments.

Outpatient Care

Because theirs is a referral center, many cancer patients come from out of town, and so there is concern about exposing nonlocal patients to COVID-19 as the virus spreads in the Seattle area. In addition, staffing shortages due to factors such as illness, exposure, and school closures are anticipated.

To address these problems, an initial priority was to establish a “multilayer” coverage system for the clinics in the event that practitioners had to be quarantined on short notice, the authors explain.

One decision was to reschedule all wellness visits for current patients or to use telemedicine. Capacity for that option expanded quickly, which was greatly helped by the recent decision by the Centers for Medicare & Medicaid Services to lift Medicare restrictions on the use of certain telemedicine services.

Another approach is to defer all consultations for second opinions for patients who were already undergoing treatment and to increase clinic hours of operations and capabilities for acute evaluations. This helps reserve emergency departments and hospital resources for patients who require higher-level care, the authors comment.

Treatment Decisions

Treatment decisions were more challenging to make, the authors note. One decision was that, despite the risk for COVID-19 for patients with solid tumors, adjuvant therapy with curative intent should proceed, they note. Similarly, patients with metastatic disease might lose the window of opportunity for treatment if it is delayed.

Treatment for aggressive hematologic malignancies is usually urgent, and stem cell transplant and cellular immunotherapies that provide curative treatments cannot be delayed in many cases.

Enrollment in clinical trials will most likely be limited to those trials that are most likely to benefit the patient.

Ueda noted that, because their patients come from all over the country, they are now conducting consultations for stem cell transplant by telephone so that nonlocal patients do not have to travel to Seattle. “If there is some way we can delay the treatment, we have taken that approach,” Ueda told Medscape Medical News. “If we can divert a patient to an area that is not as heavily affected, that’s another option we are taking.”

Although cancer surgery is not considered elective, surgical intervention needs to be prioritized, the authors comment. In the Seattle system, there is currently a 2-week ban on elective surgery in the healthcare system, owing to limited availability of personal protective equipment (PPE), staffing, and beds.

The oncology teams are currently reviewing treatment regimens to determine which treatments might lessen immunosuppression and which treatment options can be moved from the inpatient to the outpatient setting or can be delayed.

Inpatient Care

For hospitalized patients, several issues are being addressed. The priority is to prepare for an upcoming shortage of beds and resources because of the surge of patients with COVID-19 that is predicted. For both clinic and hospitalized patients, shortages of blood products have necessitated stricter adherence to thresholds for transfusion, and consideration is being given to lowering those thresholds.

Another important problem is the need to conserve PPE, which includes masks, gowns, gloves, and other products. The Seattle teams have implemented solutions such as favoring handwashing with soap and water over the use of hand gel for standard-precaution rooms, limiting the number of personnel entering patient rooms (so as to use less PPE), and reducing nursing procedures that require PPE, such as measuring urine output, unless they are necessary.

In addition, a no-visitor policy has been adopted in inpatient units to conserve PPE, with the exception of end-of-life situations.

The Future

The future trajectory of the COVID-19 pandemic is uncertain, Ueda commented. She emphasized that “we must continue to prepare for its widespread impact. The unknown is what we are looking at. We are expecting it to evolve, and the number of infections cannot go down.”

Ueda and coauthors end their article on a positive note. “To many of us, this has become the health care challenge of our generation, one that modern cancer therapy has never had to face. We will prevail, and when the pandemic ends, we will all be proud of what we did for our patients and each other in this critical moment for humanity.”

Two months after the first patient with COVID-19 was identified in China, the first case was reported in the United States in the Seattle, Washington, metropolitan area.

Seattle rapidly became the first US epicenter for COVID-19, and local experts are now offering their expertise and advice on how to provide optimal cancer care during the pandemic in a special feature published online March 20 in the Journal of the National Comprehensive Cancer Network.

“We began implementing measures in early March, including infection control and screening of visitors, staff, and patients at the door,” said lead author Masumi Ueda, MD, who holds positions at the Seattle Cancer Care Alliance, the University of Washington, and the Fred Hutchinson Research Center.

“A lot of changes have been implemented, and it changes on a daily basis. We are responding to the growing rate of COVID-19 infection in the community,” she told Medscape Medical News.

Ueda notes that as a result of the quick implementation of new procedures, so far, very few cancer patients at their facilities have been infected by the virus. “It has not hit our cancer population hard, which is a good thing,” she said.

Create “Incident Command Structure”

In sharing their experience, the authors emphasize the importance of keeping channels of communication open between all stakeholders ― administrators and staff, patients, caregivers, and the general public. They also recommend that each facility create an “incident command structure” that can provide early coordination of institution-wide efforts and that can rapidly respond to changing information.

Ueda noted that their command structure was set up very early on, “so we could get communication set up and start building an infrastructure for response.”

Several areas of care that required new strategies were addressed, both to protect patients and to work around staff shortages caused by possible exposure and/or school closings, as well as projected shortages of supplies and hospital resources.

First and foremost was to identify patients and visitors who had respiratory symptoms and to provide them with masks. Although this is always routine practice during the respiratory virus season, screening has now been initiated at entry points throughout the system.

“We were lucky in Seattle and Washington state in that the University of Washington virology lab developed PCR [polymerase chain reaction] testing early on for COVID-19, which subsequently got FDA approval,” said Ueda. “So we were able to have local testing and didn’t have to rely on the state lab. Testing has also been rapidly scaled up.”

Initiating a comprehensive policy for testing staff, tracking results and exposures for persons under investigation, and defining when it is possible to return to work are essential elements for maintaining a stable workforce. In addition, reinforcing a strict “stay at home when ill” policy and providing access to testing for symptomatic staff have been key to limiting exposures.

“What is unique to our region is that we had testing early on, and we are turning it around in 24 hours,” she pointed out. “This is important for staff to be able to return to work.” Currently, staff, patients, and visitors are being tested only if they show the cardinal symptoms associated with COVID-19: fever, shortness of breath, and cough, although muscle aches have recently been added to their testing protocol.

“I think if we had unlimited capacity, we might consider testing people who are asymptomatic,” Ueda noted, “although if you don’t have symptoms, you may not have the viral load needed for an accurate test.”

Educational materials explaining infection control were also needed for patients and families, along with signs and a website to provide COVID-19 education. These were quickly developed.

In addition, a telephone triage line was established for patients with mild symptoms in order to minimize exposures in clinics and to lessen the number of patients presenting at emergency departments.

Outpatient Care

Because theirs is a referral center, many cancer patients come from out of town, and so there is concern about exposing nonlocal patients to COVID-19 as the virus spreads in the Seattle area. In addition, staffing shortages due to factors such as illness, exposure, and school closures are anticipated.

To address these problems, an initial priority was to establish a “multilayer” coverage system for the clinics in the event that practitioners had to be quarantined on short notice, the authors explain.

One decision was to reschedule all wellness visits for current patients or to use telemedicine. Capacity for that option expanded quickly, which was greatly helped by the recent decision by the Centers for Medicare & Medicaid Services to lift Medicare restrictions on the use of certain telemedicine services.

Another approach is to defer all consultations for second opinions for patients who were already undergoing treatment and to increase clinic hours of operations and capabilities for acute evaluations. This helps reserve emergency departments and hospital resources for patients who require higher-level care, the authors comment.

Treatment Decisions

Treatment decisions were more challenging to make, the authors note. One decision was that, despite the risk for COVID-19 for patients with solid tumors, adjuvant therapy with curative intent should proceed, they note. Similarly, patients with metastatic disease might lose the window of opportunity for treatment if it is delayed.

Treatment for aggressive hematologic malignancies is usually urgent, and stem cell transplant and cellular immunotherapies that provide curative treatments cannot be delayed in many cases.

Enrollment in clinical trials will most likely be limited to those trials that are most likely to benefit the patient.

Ueda noted that, because their patients come from all over the country, they are now conducting consultations for stem cell transplant by telephone so that nonlocal patients do not have to travel to Seattle. “If there is some way we can delay the treatment, we have taken that approach,” Ueda told Medscape Medical News. “If we can divert a patient to an area that is not as heavily affected, that’s another option we are taking.”

Although cancer surgery is not considered elective, surgical intervention needs to be prioritized, the authors comment. In the Seattle system, there is currently a 2-week ban on elective surgery in the healthcare system, owing to limited availability of personal protective equipment (PPE), staffing, and beds.

The oncology teams are currently reviewing treatment regimens to determine which treatments might lessen immunosuppression and which treatment options can be moved from the inpatient to the outpatient setting or can be delayed.

Inpatient Care

For hospitalized patients, several issues are being addressed. The priority is to prepare for an upcoming shortage of beds and resources because of the surge of patients with COVID-19 that is predicted. For both clinic and hospitalized patients, shortages of blood products have necessitated stricter adherence to thresholds for transfusion, and consideration is being given to lowering those thresholds.

Another important problem is the need to conserve PPE, which includes masks, gowns, gloves, and other products. The Seattle teams have implemented solutions such as favoring handwashing with soap and water over the use of hand gel for standard-precaution rooms, limiting the number of personnel entering patient rooms (so as to use less PPE), and reducing nursing procedures that require PPE, such as measuring urine output, unless they are necessary.

In addition, a no-visitor policy has been adopted in inpatient units to conserve PPE, with the exception of end-of-life situations.

The Future

The future trajectory of the COVID-19 pandemic is uncertain, Ueda commented. She emphasized that “we must continue to prepare for its widespread impact. The unknown is what we are looking at. We are expecting it to evolve, and the number of infections cannot go down.”

Ueda and coauthors end their article on a positive note. “To many of us, this has become the health care challenge of our generation, one that modern cancer therapy has never had to face. We will prevail, and when the pandemic ends, we will all be proud of what we did for our patients and each other in this critical moment for humanity.”

As the coronavirus pandemic escalates in the United States, Medscape Oncology reached out to a group of our contributors and asked them to provide their perspective on how their oncology departments and centers are preparing. Here are their responses to a number of issues facing oncologists in the US and around the world.
 

Have you shifted nonurgent follow-up visits to telemedicine, either via video or phone?

Kathy Miller, MD, Associate Director of Indiana University Simon Cancer Center: We are reviewing our clinic schedules and identifying “routine” follow-up patients who can be rescheduled. When patients are contacted to reschedule, they are asked if they have any urgent, immediate concerns that need to be addressed before the new appointment. If yes, they are offered a virtual visit.

Don Dizon, MD, Director of Women’s Cancers, Lifespan Cancer Institute; Director of Medical Oncology, Rhode Island Hospital: We have started to do this in preparation for a surge of people with COVID-19. Patients who are in long-term follow-up (no evidence of disease at 3 years or longer, being seen annually) or those in routine surveillance after curative treatment (that is, seen every 3 months) as well as those being seen for supportive care–type visits, like sexual health or survivorship, are all being contacted and visits are being moved to telehealth.

Jeffrey S. Weber, MD, PhD, Deputy Director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center: Yes. Any follow-up, nontreatment visits are done by phone or video if the patient agrees. (They all have).
 

Have you delayed or canceled cancer surgeries?

Ravi B. Parikh, MD, MPP, Medical oncologist at the University of Pennsylvania and the Philadelphia VA Medical Center: The University of Pennsylvania has taken this seriously. We’ve canceled all elective surgeries, have ramped up our telemedicine (video and phone) capabilities significantly, are limiting our appointments mostly to on-treatment visits, and have been asked to reconsider regular scans and reviews.

Dizon: We have not done this. There are apparently differences in interpretation in what institutions might mean as “elective surgeries.” At our institution, surgery for invasive malignancies is not elective. However, this may (or will) change if resources become an issue.

Lidia Schapira, MD, Associate Professor of Medicine and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute: Delaying elective surgery is something that hospitals here have already implemented, and I imagine that this trend will spread. But it may be difficult to decide in situations that are not exactly “life-saving” but where an earlier intervention could preserve function or improve quality of life.

Mark A. Lewis, MD, Director of Gastrointestinal Oncology at Intermountain Healthcare in Utah: Cancer surgeries have not been deemed elective or delayed.

Have you delayed or altered the delivery of potentially immune-comprising treatments?

David Kerr, MD, Professor of Cancer Medicine at the University of Oxford in England: We are considering delaying initiation of our adjuvant colorectal cancer treatments, as we have data from our own QUASAR trials suggesting that patients who commence chemotherapy between 2 and 6 weeks do equally as well as those who begin 6-12 weeks after surgery.

Parikh: I personally haven’t delayed giving chemotherapy to avoid immune compromise, but I believe some others may have. It’s a delicate balance between wanting to ensure cancer control and making sure we are flattening the curve. As an example, though, I delayed three on-treatment visits for my clinic last Monday, and I converted 70% of my visits to telemedicine. However, I’m a genitourinary cancer specialist and the treatments I give are very different from others.

Lewis: The most difficult calculus is around adjuvant therapy. For metastatic patients, I am trying to use the least immunosuppressive regimen possible that will still control their disease. As you can imagine, it’s an assessment of competing risks.

Schapira: Patients who need essential anticancer therapy should still get it, but attempts to deintensify therapy should continue—for example, holding or postponing treatment without harm (based on evidence, not opinion). This may be possible for patients considering hormonal therapies for breast or prostate cancer.

Patients who need radiation should discuss the timing with their radiation oncologist. In some cases, it may be possible to delay treatment without affecting outcomes, but these decisions should be made carefully. Alternatively, shorter courses of radiation may be appropriate.
 

Have you advised your own patients differently given the high risk to cancer patients?

Kerr: We have factored potential infection with the virus into discussions where the benefits of chemotherapy are very marginal. This could tip the balance toward the patient deciding not to pursue chemotherapy.

Dizon: The data from China are not entirely crystal-clear. While they noted that people with active cancer and those who had a history of cancer are at increased risk for more severe infections and worse outcomes, the Chinese cohort was small, and compared with people without cancer, it tended to be much older and to be smokers (former or current). Having said this, we are counseling everyone about the importance of social distancing, washing hands, and not touching your face.

Lewis: If I have a complete blood count with a differential that includes lymphocytes, I can advise my lymphopenic patients (who are particularly vulnerable to viral infection) to take special precautions regarding social distancing in their own families.
 

Have any of your hospitalized patients been affected by policy changes to prepare beds/departments for the expected increase in COVID-19–positive patients?

Weber: Not yet.

Dizon: No, not at the moment.
 

Have you been asked to assist with other services or COVID-19 task forces?

Dizon: I am keenly involved in the preparations and modifications to procedures, including staffing decisions in outpatient, movement to telehealth, and work-from-home policies.

Lewis: I am engaged in system-wide COVID-19 efforts around oncology.

Kerr: Perhaps oddest of all, I am learning with some of our junior doctors to care for ventilated patients. I still consider myself enough of a general physician that I would hope to be able to contribute to the truly sick, but I accept that I do need an appropriate refresher course.

Bishal Gyawali, MD, PhD, medical oncologist at Queen’s University Cancer Research Institute: Queen’s Hospital medical students are now volunteering to help with daycare, groceries, and other tasks for staff who are working in the hospital.
 

Are you experiencing any shortages in personal protective equipment (PPE) at your center?

Miller: Some supplies are running short, though none are frankly out at this point. However, rationing and controls are in place to stretch the supplies as far as possible, including reusing some PPE.

Dizon: We are rationing face masks and N95 respirators, eye shields, and even surgical scrubs. We are talking about postponing elective surgery to save PPE but are not yet to that point. We’re asking that face masks be reused for at least 2 days, maybe longer. PPEs are one per day. Scrubs are kept secure.

Lewis: We are being very careful not to overuse PPE but currently have an adequate inventory. We have had to move gloves and masks to areas where they are not accessible to the general public, as otherwise they were being stolen (this started weeks ago).

Kerr: Our National Health System has an adequate supply of PPE equipment centrally, but there seems to be a problem with distribution, as some hospitals are reporting shortages.

Weber: Masks are in short supply, so they are being used for several days if not wet. We are short of plastic gowns and are using paper chemo gowns. Similar story at many places.

This article first appeared on Medscape.com.

As the coronavirus pandemic escalates in the United States, Medscape Oncology reached out to a group of our contributors and asked them to provide their perspective on how their oncology departments and centers are preparing. Here are their responses to a number of issues facing oncologists in the US and around the world.
 

Have you shifted nonurgent follow-up visits to telemedicine, either via video or phone?

Kathy Miller, MD, Associate Director of Indiana University Simon Cancer Center: We are reviewing our clinic schedules and identifying “routine” follow-up patients who can be rescheduled. When patients are contacted to reschedule, they are asked if they have any urgent, immediate concerns that need to be addressed before the new appointment. If yes, they are offered a virtual visit.

Don Dizon, MD, Director of Women’s Cancers, Lifespan Cancer Institute; Director of Medical Oncology, Rhode Island Hospital: We have started to do this in preparation for a surge of people with COVID-19. Patients who are in long-term follow-up (no evidence of disease at 3 years or longer, being seen annually) or those in routine surveillance after curative treatment (that is, seen every 3 months) as well as those being seen for supportive care–type visits, like sexual health or survivorship, are all being contacted and visits are being moved to telehealth.

Jeffrey S. Weber, MD, PhD, Deputy Director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center: Yes. Any follow-up, nontreatment visits are done by phone or video if the patient agrees. (They all have).
 

Have you delayed or canceled cancer surgeries?

Ravi B. Parikh, MD, MPP, Medical oncologist at the University of Pennsylvania and the Philadelphia VA Medical Center: The University of Pennsylvania has taken this seriously. We’ve canceled all elective surgeries, have ramped up our telemedicine (video and phone) capabilities significantly, are limiting our appointments mostly to on-treatment visits, and have been asked to reconsider regular scans and reviews.

Dizon: We have not done this. There are apparently differences in interpretation in what institutions might mean as “elective surgeries.” At our institution, surgery for invasive malignancies is not elective. However, this may (or will) change if resources become an issue.

Lidia Schapira, MD, Associate Professor of Medicine and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute: Delaying elective surgery is something that hospitals here have already implemented, and I imagine that this trend will spread. But it may be difficult to decide in situations that are not exactly “life-saving” but where an earlier intervention could preserve function or improve quality of life.

Mark A. Lewis, MD, Director of Gastrointestinal Oncology at Intermountain Healthcare in Utah: Cancer surgeries have not been deemed elective or delayed.

Have you delayed or altered the delivery of potentially immune-comprising treatments?

David Kerr, MD, Professor of Cancer Medicine at the University of Oxford in England: We are considering delaying initiation of our adjuvant colorectal cancer treatments, as we have data from our own QUASAR trials suggesting that patients who commence chemotherapy between 2 and 6 weeks do equally as well as those who begin 6-12 weeks after surgery.

Parikh: I personally haven’t delayed giving chemotherapy to avoid immune compromise, but I believe some others may have. It’s a delicate balance between wanting to ensure cancer control and making sure we are flattening the curve. As an example, though, I delayed three on-treatment visits for my clinic last Monday, and I converted 70% of my visits to telemedicine. However, I’m a genitourinary cancer specialist and the treatments I give are very different from others.

Lewis: The most difficult calculus is around adjuvant therapy. For metastatic patients, I am trying to use the least immunosuppressive regimen possible that will still control their disease. As you can imagine, it’s an assessment of competing risks.

Schapira: Patients who need essential anticancer therapy should still get it, but attempts to deintensify therapy should continue—for example, holding or postponing treatment without harm (based on evidence, not opinion). This may be possible for patients considering hormonal therapies for breast or prostate cancer.

Patients who need radiation should discuss the timing with their radiation oncologist. In some cases, it may be possible to delay treatment without affecting outcomes, but these decisions should be made carefully. Alternatively, shorter courses of radiation may be appropriate.
 

Have you advised your own patients differently given the high risk to cancer patients?

Kerr: We have factored potential infection with the virus into discussions where the benefits of chemotherapy are very marginal. This could tip the balance toward the patient deciding not to pursue chemotherapy.

Dizon: The data from China are not entirely crystal-clear. While they noted that people with active cancer and those who had a history of cancer are at increased risk for more severe infections and worse outcomes, the Chinese cohort was small, and compared with people without cancer, it tended to be much older and to be smokers (former or current). Having said this, we are counseling everyone about the importance of social distancing, washing hands, and not touching your face.

Lewis: If I have a complete blood count with a differential that includes lymphocytes, I can advise my lymphopenic patients (who are particularly vulnerable to viral infection) to take special precautions regarding social distancing in their own families.
 

Have any of your hospitalized patients been affected by policy changes to prepare beds/departments for the expected increase in COVID-19–positive patients?

Weber: Not yet.

Dizon: No, not at the moment.
 

Have you been asked to assist with other services or COVID-19 task forces?

Dizon: I am keenly involved in the preparations and modifications to procedures, including staffing decisions in outpatient, movement to telehealth, and work-from-home policies.

Lewis: I am engaged in system-wide COVID-19 efforts around oncology.

Kerr: Perhaps oddest of all, I am learning with some of our junior doctors to care for ventilated patients. I still consider myself enough of a general physician that I would hope to be able to contribute to the truly sick, but I accept that I do need an appropriate refresher course.

Bishal Gyawali, MD, PhD, medical oncologist at Queen’s University Cancer Research Institute: Queen’s Hospital medical students are now volunteering to help with daycare, groceries, and other tasks for staff who are working in the hospital.
 

Are you experiencing any shortages in personal protective equipment (PPE) at your center?

Miller: Some supplies are running short, though none are frankly out at this point. However, rationing and controls are in place to stretch the supplies as far as possible, including reusing some PPE.

Dizon: We are rationing face masks and N95 respirators, eye shields, and even surgical scrubs. We are talking about postponing elective surgery to save PPE but are not yet to that point. We’re asking that face masks be reused for at least 2 days, maybe longer. PPEs are one per day. Scrubs are kept secure.

Lewis: We are being very careful not to overuse PPE but currently have an adequate inventory. We have had to move gloves and masks to areas where they are not accessible to the general public, as otherwise they were being stolen (this started weeks ago).

Kerr: Our National Health System has an adequate supply of PPE equipment centrally, but there seems to be a problem with distribution, as some hospitals are reporting shortages.

Weber: Masks are in short supply, so they are being used for several days if not wet. We are short of plastic gowns and are using paper chemo gowns. Similar story at many places.

This article first appeared on Medscape.com.

As the coronavirus pandemic escalates in the United States, Medscape Oncology reached out to a group of our contributors and asked them to provide their perspective on how their oncology departments and centers are preparing. Here are their responses to a number of issues facing oncologists in the US and around the world.
 

Have you shifted nonurgent follow-up visits to telemedicine, either via video or phone?

Kathy Miller, MD, Associate Director of Indiana University Simon Cancer Center: We are reviewing our clinic schedules and identifying “routine” follow-up patients who can be rescheduled. When patients are contacted to reschedule, they are asked if they have any urgent, immediate concerns that need to be addressed before the new appointment. If yes, they are offered a virtual visit.

Don Dizon, MD, Director of Women’s Cancers, Lifespan Cancer Institute; Director of Medical Oncology, Rhode Island Hospital: We have started to do this in preparation for a surge of people with COVID-19. Patients who are in long-term follow-up (no evidence of disease at 3 years or longer, being seen annually) or those in routine surveillance after curative treatment (that is, seen every 3 months) as well as those being seen for supportive care–type visits, like sexual health or survivorship, are all being contacted and visits are being moved to telehealth.

Jeffrey S. Weber, MD, PhD, Deputy Director of the Laura and Isaac Perlmutter Cancer Center at NYU Langone Medical Center: Yes. Any follow-up, nontreatment visits are done by phone or video if the patient agrees. (They all have).
 

Have you delayed or canceled cancer surgeries?

Ravi B. Parikh, MD, MPP, Medical oncologist at the University of Pennsylvania and the Philadelphia VA Medical Center: The University of Pennsylvania has taken this seriously. We’ve canceled all elective surgeries, have ramped up our telemedicine (video and phone) capabilities significantly, are limiting our appointments mostly to on-treatment visits, and have been asked to reconsider regular scans and reviews.

Dizon: We have not done this. There are apparently differences in interpretation in what institutions might mean as “elective surgeries.” At our institution, surgery for invasive malignancies is not elective. However, this may (or will) change if resources become an issue.

Lidia Schapira, MD, Associate Professor of Medicine and Director of Cancer Survivorship at the Stanford Comprehensive Cancer Institute: Delaying elective surgery is something that hospitals here have already implemented, and I imagine that this trend will spread. But it may be difficult to decide in situations that are not exactly “life-saving” but where an earlier intervention could preserve function or improve quality of life.

Mark A. Lewis, MD, Director of Gastrointestinal Oncology at Intermountain Healthcare in Utah: Cancer surgeries have not been deemed elective or delayed.

Have you delayed or altered the delivery of potentially immune-comprising treatments?

David Kerr, MD, Professor of Cancer Medicine at the University of Oxford in England: We are considering delaying initiation of our adjuvant colorectal cancer treatments, as we have data from our own QUASAR trials suggesting that patients who commence chemotherapy between 2 and 6 weeks do equally as well as those who begin 6-12 weeks after surgery.

Parikh: I personally haven’t delayed giving chemotherapy to avoid immune compromise, but I believe some others may have. It’s a delicate balance between wanting to ensure cancer control and making sure we are flattening the curve. As an example, though, I delayed three on-treatment visits for my clinic last Monday, and I converted 70% of my visits to telemedicine. However, I’m a genitourinary cancer specialist and the treatments I give are very different from others.

Lewis: The most difficult calculus is around adjuvant therapy. For metastatic patients, I am trying to use the least immunosuppressive regimen possible that will still control their disease. As you can imagine, it’s an assessment of competing risks.

Schapira: Patients who need essential anticancer therapy should still get it, but attempts to deintensify therapy should continue—for example, holding or postponing treatment without harm (based on evidence, not opinion). This may be possible for patients considering hormonal therapies for breast or prostate cancer.

Patients who need radiation should discuss the timing with their radiation oncologist. In some cases, it may be possible to delay treatment without affecting outcomes, but these decisions should be made carefully. Alternatively, shorter courses of radiation may be appropriate.
 

Have you advised your own patients differently given the high risk to cancer patients?

Kerr: We have factored potential infection with the virus into discussions where the benefits of chemotherapy are very marginal. This could tip the balance toward the patient deciding not to pursue chemotherapy.

Dizon: The data from China are not entirely crystal-clear. While they noted that people with active cancer and those who had a history of cancer are at increased risk for more severe infections and worse outcomes, the Chinese cohort was small, and compared with people without cancer, it tended to be much older and to be smokers (former or current). Having said this, we are counseling everyone about the importance of social distancing, washing hands, and not touching your face.

Lewis: If I have a complete blood count with a differential that includes lymphocytes, I can advise my lymphopenic patients (who are particularly vulnerable to viral infection) to take special precautions regarding social distancing in their own families.
 

Have any of your hospitalized patients been affected by policy changes to prepare beds/departments for the expected increase in COVID-19–positive patients?

Weber: Not yet.

Dizon: No, not at the moment.
 

Have you been asked to assist with other services or COVID-19 task forces?

Dizon: I am keenly involved in the preparations and modifications to procedures, including staffing decisions in outpatient, movement to telehealth, and work-from-home policies.

Lewis: I am engaged in system-wide COVID-19 efforts around oncology.

Kerr: Perhaps oddest of all, I am learning with some of our junior doctors to care for ventilated patients. I still consider myself enough of a general physician that I would hope to be able to contribute to the truly sick, but I accept that I do need an appropriate refresher course.

Bishal Gyawali, MD, PhD, medical oncologist at Queen’s University Cancer Research Institute: Queen’s Hospital medical students are now volunteering to help with daycare, groceries, and other tasks for staff who are working in the hospital.
 

Are you experiencing any shortages in personal protective equipment (PPE) at your center?

Miller: Some supplies are running short, though none are frankly out at this point. However, rationing and controls are in place to stretch the supplies as far as possible, including reusing some PPE.

Dizon: We are rationing face masks and N95 respirators, eye shields, and even surgical scrubs. We are talking about postponing elective surgery to save PPE but are not yet to that point. We’re asking that face masks be reused for at least 2 days, maybe longer. PPEs are one per day. Scrubs are kept secure.

Lewis: We are being very careful not to overuse PPE but currently have an adequate inventory. We have had to move gloves and masks to areas where they are not accessible to the general public, as otherwise they were being stolen (this started weeks ago).

Kerr: Our National Health System has an adequate supply of PPE equipment centrally, but there seems to be a problem with distribution, as some hospitals are reporting shortages.

Weber: Masks are in short supply, so they are being used for several days if not wet. We are short of plastic gowns and are using paper chemo gowns. Similar story at many places.

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
 

Even in the midst of the COVID-19 pandemic, cancer care must go on, but changes may need to be made in the way some care is delivered.

“We’re headed for a time when there will be significant disruptions in the care of patients with cancer,” said Len Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society (ACS), in a statement. “For some it may be as straightforward as a delay in having elective surgery. For others it may be delaying preventive care or adjuvant chemotherapy that’s meant to keep cancer from returning or rescheduling appointments.”

Lichtenfeld emphasized that cancer care teams are going to do the best they can to deliver care to those most in need. However, even in those circumstances, it won’t be life as usual. “It will require patience on everyone’s part as we go through this pandemic,” he said.

“The way we treat cancer over the next few months will change enormously,” writes a British oncologist in an article published in the Guardian.

“As oncologists, we will have to find a tenuous balance between undertreating people with cancer, resulting in more deaths from the disease in the medium to long term, and increasing deaths from COVID-19 in a vulnerable patient population. Alongside our patients we will have to make difficult decisions regarding treatments, with only low-quality evidence to guide us,” writes Lucy Gossage, MD, consultant oncologist at Nottingham University Hospital, UK.

The evidence to date (from reports from China in Lancet Oncology) suggests that people with cancer have a significantly higher risk of severe illness resulting in intensive care admissions or death when infected with COVID-19, particularly if they recently had chemotherapy or surgery.

“Many of the oncology treatments we currently use, especially those given after surgery to reduce risk of cancer recurrence, have relatively small benefits,” she writes.

“In the current climate, the balance of offering these treatments may shift; a small reduction in risk of cancer recurrence over the next 5 years may be outweighed by the potential for a short-term increase in risk of death from COVID-19. In the long term, more people’s cancer will return if we aren’t able to offer these treatments,” she adds.

Postpone Routine Screening

One thing that can go on the back burner for now is routine cancer screening, which can be postponed for now in order to conserve health system resources and reduce contact with healthcare facilities, says the ACS.

“Patients seeking routine cancer screenings should delay those until further notice,” said Lichtenfeld. “While timely screening is important, the need to prevent the spread of coronavirus and to reduce the strain on the medical system is more important right now.”

But as soon as restrictions to slow the spread of COVID-19 are lifted and routine visits to health facilities are safe, regular screening tests should be rescheduled.

Guidance From ASCO

The American Society of Clinical Oncology (ASCO) has issued new guidance on caring for patients with cancer during the COVID-19 outbreak.

First and foremost, ASCO encourages providers, facilities, and anyone caring for patients with cancer to follow the existing guidelines from the Center for Disease Control and Prevention when possible.

ASCO highlights the CDC’s general recommendation for healthcare facilities that suggests “elective surgeries” at inpatient facilities be rescheduled if possible, which has also been recommended by the American College of Surgeons.

However, in many cases, cancer surgery is not elective but essential, it points out. So this is largely an individual determination that clinicians and patients will need to make, taking into account the potential harms of delaying needed cancer-related surgery.

Systemic treatments, including chemotherapy and immunotherapy, leave cancer patients vulnerable to infection, but ASCO says there is no direct evidence to support changes in regimens during the pandemic. Therefore, routinely stopping anticancer or immunosuppressive therapy is not recommended, as the balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection remains very unclear.

Clinical decisions must be individualized, ASCO emphasized, and suggested the following practice points be considered:

• For patients already in deep remission who are receiving maintenance therapy, stopping treatment may be an option.
• Some patients may be able to switch from IV to oral therapies, which would decrease the frequency of clinic visits.
• Decisions on modifying or withholding chemotherapy need to consider both the indication and goals of care, as well as where the patient is in the treatment regimen and tolerance to the therapy. As an example, the risk–benefit assessment for proceeding with chemotherapy in patients with untreated extensive small-cell lung cancer is quite different than proceeding with maintenance pemetrexed for metastatic non–small cell lung cancer.
• If local coronavirus transmission is an issue at a particular cancer center, reasonable options may include taking a 2-week treatment break or arranging treatment at a different facility.
• Evaluate if home infusion is medically and logistically feasible.
• In some settings, delaying or modifying adjuvant treatment presents a higher risk of compromised disease control and long-term survival than in others, but in cases where the absolute benefit of adjuvant chemotherapy may be quite small and other options are available, the risk of COVID-19 may be considered an additional factor when evaluating care.

Delay Stem Cell Transplants

For patients who are candidates for allogeneic stem cell transplantation, a delay may be reasonable if the patient is currently well controlled with conventional treatment, ASCO comments. It also directs clinicians to follow the recommendations provided by the American Society of Transplantation and Cellular Therapy and from the European Society for Blood and Marrow Transplantation regarding this issue.

Finally, there is also the question of prophylactic antiviral therapy: Should it be considered for cancer patients undergoing active therapy?

The answer to that question is currently unknown, says ASCO, but “this is an active area of research and evidence may be available at any time.”

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
 

Even in the midst of the COVID-19 pandemic, cancer care must go on, but changes may need to be made in the way some care is delivered.

“We’re headed for a time when there will be significant disruptions in the care of patients with cancer,” said Len Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society (ACS), in a statement. “For some it may be as straightforward as a delay in having elective surgery. For others it may be delaying preventive care or adjuvant chemotherapy that’s meant to keep cancer from returning or rescheduling appointments.”

Lichtenfeld emphasized that cancer care teams are going to do the best they can to deliver care to those most in need. However, even in those circumstances, it won’t be life as usual. “It will require patience on everyone’s part as we go through this pandemic,” he said.

“The way we treat cancer over the next few months will change enormously,” writes a British oncologist in an article published in the Guardian.

“As oncologists, we will have to find a tenuous balance between undertreating people with cancer, resulting in more deaths from the disease in the medium to long term, and increasing deaths from COVID-19 in a vulnerable patient population. Alongside our patients we will have to make difficult decisions regarding treatments, with only low-quality evidence to guide us,” writes Lucy Gossage, MD, consultant oncologist at Nottingham University Hospital, UK.

The evidence to date (from reports from China in Lancet Oncology) suggests that people with cancer have a significantly higher risk of severe illness resulting in intensive care admissions or death when infected with COVID-19, particularly if they recently had chemotherapy or surgery.

“Many of the oncology treatments we currently use, especially those given after surgery to reduce risk of cancer recurrence, have relatively small benefits,” she writes.

“In the current climate, the balance of offering these treatments may shift; a small reduction in risk of cancer recurrence over the next 5 years may be outweighed by the potential for a short-term increase in risk of death from COVID-19. In the long term, more people’s cancer will return if we aren’t able to offer these treatments,” she adds.

Postpone Routine Screening

One thing that can go on the back burner for now is routine cancer screening, which can be postponed for now in order to conserve health system resources and reduce contact with healthcare facilities, says the ACS.

“Patients seeking routine cancer screenings should delay those until further notice,” said Lichtenfeld. “While timely screening is important, the need to prevent the spread of coronavirus and to reduce the strain on the medical system is more important right now.”

But as soon as restrictions to slow the spread of COVID-19 are lifted and routine visits to health facilities are safe, regular screening tests should be rescheduled.

Guidance From ASCO

The American Society of Clinical Oncology (ASCO) has issued new guidance on caring for patients with cancer during the COVID-19 outbreak.

First and foremost, ASCO encourages providers, facilities, and anyone caring for patients with cancer to follow the existing guidelines from the Center for Disease Control and Prevention when possible.

ASCO highlights the CDC’s general recommendation for healthcare facilities that suggests “elective surgeries” at inpatient facilities be rescheduled if possible, which has also been recommended by the American College of Surgeons.

However, in many cases, cancer surgery is not elective but essential, it points out. So this is largely an individual determination that clinicians and patients will need to make, taking into account the potential harms of delaying needed cancer-related surgery.

Systemic treatments, including chemotherapy and immunotherapy, leave cancer patients vulnerable to infection, but ASCO says there is no direct evidence to support changes in regimens during the pandemic. Therefore, routinely stopping anticancer or immunosuppressive therapy is not recommended, as the balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection remains very unclear.

Clinical decisions must be individualized, ASCO emphasized, and suggested the following practice points be considered:

• For patients already in deep remission who are receiving maintenance therapy, stopping treatment may be an option.
• Some patients may be able to switch from IV to oral therapies, which would decrease the frequency of clinic visits.
• Decisions on modifying or withholding chemotherapy need to consider both the indication and goals of care, as well as where the patient is in the treatment regimen and tolerance to the therapy. As an example, the risk–benefit assessment for proceeding with chemotherapy in patients with untreated extensive small-cell lung cancer is quite different than proceeding with maintenance pemetrexed for metastatic non–small cell lung cancer.
• If local coronavirus transmission is an issue at a particular cancer center, reasonable options may include taking a 2-week treatment break or arranging treatment at a different facility.
• Evaluate if home infusion is medically and logistically feasible.
• In some settings, delaying or modifying adjuvant treatment presents a higher risk of compromised disease control and long-term survival than in others, but in cases where the absolute benefit of adjuvant chemotherapy may be quite small and other options are available, the risk of COVID-19 may be considered an additional factor when evaluating care.

Delay Stem Cell Transplants

For patients who are candidates for allogeneic stem cell transplantation, a delay may be reasonable if the patient is currently well controlled with conventional treatment, ASCO comments. It also directs clinicians to follow the recommendations provided by the American Society of Transplantation and Cellular Therapy and from the European Society for Blood and Marrow Transplantation regarding this issue.

Finally, there is also the question of prophylactic antiviral therapy: Should it be considered for cancer patients undergoing active therapy?

The answer to that question is currently unknown, says ASCO, but “this is an active area of research and evidence may be available at any time.”

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s Coronavirus Resource Center.
 

Even in the midst of the COVID-19 pandemic, cancer care must go on, but changes may need to be made in the way some care is delivered.

“We’re headed for a time when there will be significant disruptions in the care of patients with cancer,” said Len Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society (ACS), in a statement. “For some it may be as straightforward as a delay in having elective surgery. For others it may be delaying preventive care or adjuvant chemotherapy that’s meant to keep cancer from returning or rescheduling appointments.”

Lichtenfeld emphasized that cancer care teams are going to do the best they can to deliver care to those most in need. However, even in those circumstances, it won’t be life as usual. “It will require patience on everyone’s part as we go through this pandemic,” he said.

“The way we treat cancer over the next few months will change enormously,” writes a British oncologist in an article published in the Guardian.

“As oncologists, we will have to find a tenuous balance between undertreating people with cancer, resulting in more deaths from the disease in the medium to long term, and increasing deaths from COVID-19 in a vulnerable patient population. Alongside our patients we will have to make difficult decisions regarding treatments, with only low-quality evidence to guide us,” writes Lucy Gossage, MD, consultant oncologist at Nottingham University Hospital, UK.

The evidence to date (from reports from China in Lancet Oncology) suggests that people with cancer have a significantly higher risk of severe illness resulting in intensive care admissions or death when infected with COVID-19, particularly if they recently had chemotherapy or surgery.

“Many of the oncology treatments we currently use, especially those given after surgery to reduce risk of cancer recurrence, have relatively small benefits,” she writes.

“In the current climate, the balance of offering these treatments may shift; a small reduction in risk of cancer recurrence over the next 5 years may be outweighed by the potential for a short-term increase in risk of death from COVID-19. In the long term, more people’s cancer will return if we aren’t able to offer these treatments,” she adds.

Postpone Routine Screening

One thing that can go on the back burner for now is routine cancer screening, which can be postponed for now in order to conserve health system resources and reduce contact with healthcare facilities, says the ACS.

“Patients seeking routine cancer screenings should delay those until further notice,” said Lichtenfeld. “While timely screening is important, the need to prevent the spread of coronavirus and to reduce the strain on the medical system is more important right now.”

But as soon as restrictions to slow the spread of COVID-19 are lifted and routine visits to health facilities are safe, regular screening tests should be rescheduled.

Guidance From ASCO

The American Society of Clinical Oncology (ASCO) has issued new guidance on caring for patients with cancer during the COVID-19 outbreak.

First and foremost, ASCO encourages providers, facilities, and anyone caring for patients with cancer to follow the existing guidelines from the Center for Disease Control and Prevention when possible.

ASCO highlights the CDC’s general recommendation for healthcare facilities that suggests “elective surgeries” at inpatient facilities be rescheduled if possible, which has also been recommended by the American College of Surgeons.

However, in many cases, cancer surgery is not elective but essential, it points out. So this is largely an individual determination that clinicians and patients will need to make, taking into account the potential harms of delaying needed cancer-related surgery.

Systemic treatments, including chemotherapy and immunotherapy, leave cancer patients vulnerable to infection, but ASCO says there is no direct evidence to support changes in regimens during the pandemic. Therefore, routinely stopping anticancer or immunosuppressive therapy is not recommended, as the balance of potential harms that may result from delaying or interrupting treatment versus the potential benefits of possibly preventing or delaying COVID-19 infection remains very unclear.

Clinical decisions must be individualized, ASCO emphasized, and suggested the following practice points be considered:

• For patients already in deep remission who are receiving maintenance therapy, stopping treatment may be an option.
• Some patients may be able to switch from IV to oral therapies, which would decrease the frequency of clinic visits.
• Decisions on modifying or withholding chemotherapy need to consider both the indication and goals of care, as well as where the patient is in the treatment regimen and tolerance to the therapy. As an example, the risk–benefit assessment for proceeding with chemotherapy in patients with untreated extensive small-cell lung cancer is quite different than proceeding with maintenance pemetrexed for metastatic non–small cell lung cancer.
• If local coronavirus transmission is an issue at a particular cancer center, reasonable options may include taking a 2-week treatment break or arranging treatment at a different facility.
• Evaluate if home infusion is medically and logistically feasible.
• In some settings, delaying or modifying adjuvant treatment presents a higher risk of compromised disease control and long-term survival than in others, but in cases where the absolute benefit of adjuvant chemotherapy may be quite small and other options are available, the risk of COVID-19 may be considered an additional factor when evaluating care.

Delay Stem Cell Transplants

For patients who are candidates for allogeneic stem cell transplantation, a delay may be reasonable if the patient is currently well controlled with conventional treatment, ASCO comments. It also directs clinicians to follow the recommendations provided by the American Society of Transplantation and Cellular Therapy and from the European Society for Blood and Marrow Transplantation regarding this issue.

Finally, there is also the question of prophylactic antiviral therapy: Should it be considered for cancer patients undergoing active therapy?

The answer to that question is currently unknown, says ASCO, but “this is an active area of research and evidence may be available at any time.”

This article first appeared on Medscape.com.

The biggest cancer research meeting of the year has been canceled as a reaction to the novel coronavirus (COVID-19) outbreak, which has also led to many other medical conferences being canceled or postponed.

The annual meeting of the American Association for Cancer Research (AACR) was due to take place April 24-29 in San Diego, California. More than 24,000 delegates from 80 countries and more than 500 exhibitors were expected to attend.

There are plans to reschedule it for later this year.

This has been a “difficult decision,” said the AACR board of directors, but “we believe that the decision to postpone the meeting is absolutely the correct one to safeguard our meeting participants from further potential exposure to the coronavirus.”

The board goes on to explain that “this evidence-based decision was made after a thorough review and discussion of all factors impacting the annual meeting, including the US government’s enforcement of restrictions on international travelers to enter the US; the imposition of travel restrictions issued by US government agencies, cancer centers, academic institutions, and pharmaceutical and biotech companies; and the counsel of infectious disease experts. It is clear that all of these elements significantly affect the ability of delegates, speakers, presenters of proffered papers, and exhibitors to participate fully in the annual meeting.”

Other cancer conferences that were planned for March and that have been canceled include the following:

• European Breast Cancer Conference (EBCC), Barcelona, Spain, which was to have taken place March 18-20. This conference has been postponed and will now take place September 30 to October 2 at the same venue. Abstracts that have been accepted for the initial conference will remain in the program, and organizers will reopen abstract submissions in May.
• National Comprehensive Cancer Network (NCCN), Orlando, Florida, was scheduled for March 19-22. This conference has been postponed. No new dates have been provided, but the society notes that “NCCN staff is working as quickly as possible to notify all conference registrants about the postponement and further information regarding the refund process.”
• European Association of Urology (EAU), Amsterdam, the Netherlands, at which there is always new research presented on prostate, kidney, and bladder cancer, was due to take place March 20-24. This conference has been postponed to July 2020.
• Society of Gynecologic Oncology (SGO), in Toronto, Canada, which was scheduled for March 28-31. SGO is “exploring alternatives for delivering the science and education.”

Overall, the move to cancel medical conferences over the next few months is a good idea, commented F. Perry Wilson, MD, MSCE, associate professor of medicine and director of Yale’s Program of Applied Translational Research, in a Medscape Medical News commentary.

“There’s a pretty straightforward case here,” he argued. “Medical professionals are at higher risk for exposure to coronavirus because we come into contact with lots and lots of patients. Gathering a large group of medical professionals in a single place increases the risk for exposure further. Factor in airplane flights to and from the conferences, and the chance that infection is spread is significant.”

This article first appeared on Medscape.com.

The biggest cancer research meeting of the year has been canceled as a reaction to the novel coronavirus (COVID-19) outbreak, which has also led to many other medical conferences being canceled or postponed.

The annual meeting of the American Association for Cancer Research (AACR) was due to take place April 24-29 in San Diego, California. More than 24,000 delegates from 80 countries and more than 500 exhibitors were expected to attend.

There are plans to reschedule it for later this year.

This has been a “difficult decision,” said the AACR board of directors, but “we believe that the decision to postpone the meeting is absolutely the correct one to safeguard our meeting participants from further potential exposure to the coronavirus.”

The board goes on to explain that “this evidence-based decision was made after a thorough review and discussion of all factors impacting the annual meeting, including the US government’s enforcement of restrictions on international travelers to enter the US; the imposition of travel restrictions issued by US government agencies, cancer centers, academic institutions, and pharmaceutical and biotech companies; and the counsel of infectious disease experts. It is clear that all of these elements significantly affect the ability of delegates, speakers, presenters of proffered papers, and exhibitors to participate fully in the annual meeting.”

Other cancer conferences that were planned for March and that have been canceled include the following:

• European Breast Cancer Conference (EBCC), Barcelona, Spain, which was to have taken place March 18-20. This conference has been postponed and will now take place September 30 to October 2 at the same venue. Abstracts that have been accepted for the initial conference will remain in the program, and organizers will reopen abstract submissions in May.
• National Comprehensive Cancer Network (NCCN), Orlando, Florida, was scheduled for March 19-22. This conference has been postponed. No new dates have been provided, but the society notes that “NCCN staff is working as quickly as possible to notify all conference registrants about the postponement and further information regarding the refund process.”
• European Association of Urology (EAU), Amsterdam, the Netherlands, at which there is always new research presented on prostate, kidney, and bladder cancer, was due to take place March 20-24. This conference has been postponed to July 2020.
• Society of Gynecologic Oncology (SGO), in Toronto, Canada, which was scheduled for March 28-31. SGO is “exploring alternatives for delivering the science and education.”

Overall, the move to cancel medical conferences over the next few months is a good idea, commented F. Perry Wilson, MD, MSCE, associate professor of medicine and director of Yale’s Program of Applied Translational Research, in a Medscape Medical News commentary.

“There’s a pretty straightforward case here,” he argued. “Medical professionals are at higher risk for exposure to coronavirus because we come into contact with lots and lots of patients. Gathering a large group of medical professionals in a single place increases the risk for exposure further. Factor in airplane flights to and from the conferences, and the chance that infection is spread is significant.”

This article first appeared on Medscape.com.

The biggest cancer research meeting of the year has been canceled as a reaction to the novel coronavirus (COVID-19) outbreak, which has also led to many other medical conferences being canceled or postponed.

The annual meeting of the American Association for Cancer Research (AACR) was due to take place April 24-29 in San Diego, California. More than 24,000 delegates from 80 countries and more than 500 exhibitors were expected to attend.

There are plans to reschedule it for later this year.

This has been a “difficult decision,” said the AACR board of directors, but “we believe that the decision to postpone the meeting is absolutely the correct one to safeguard our meeting participants from further potential exposure to the coronavirus.”

The board goes on to explain that “this evidence-based decision was made after a thorough review and discussion of all factors impacting the annual meeting, including the US government’s enforcement of restrictions on international travelers to enter the US; the imposition of travel restrictions issued by US government agencies, cancer centers, academic institutions, and pharmaceutical and biotech companies; and the counsel of infectious disease experts. It is clear that all of these elements significantly affect the ability of delegates, speakers, presenters of proffered papers, and exhibitors to participate fully in the annual meeting.”

Other cancer conferences that were planned for March and that have been canceled include the following:

• European Breast Cancer Conference (EBCC), Barcelona, Spain, which was to have taken place March 18-20. This conference has been postponed and will now take place September 30 to October 2 at the same venue. Abstracts that have been accepted for the initial conference will remain in the program, and organizers will reopen abstract submissions in May.
• National Comprehensive Cancer Network (NCCN), Orlando, Florida, was scheduled for March 19-22. This conference has been postponed. No new dates have been provided, but the society notes that “NCCN staff is working as quickly as possible to notify all conference registrants about the postponement and further information regarding the refund process.”
• European Association of Urology (EAU), Amsterdam, the Netherlands, at which there is always new research presented on prostate, kidney, and bladder cancer, was due to take place March 20-24. This conference has been postponed to July 2020.
• Society of Gynecologic Oncology (SGO), in Toronto, Canada, which was scheduled for March 28-31. SGO is “exploring alternatives for delivering the science and education.”

Overall, the move to cancel medical conferences over the next few months is a good idea, commented F. Perry Wilson, MD, MSCE, associate professor of medicine and director of Yale’s Program of Applied Translational Research, in a Medscape Medical News commentary.

“There’s a pretty straightforward case here,” he argued. “Medical professionals are at higher risk for exposure to coronavirus because we come into contact with lots and lots of patients. Gathering a large group of medical professionals in a single place increases the risk for exposure further. Factor in airplane flights to and from the conferences, and the chance that infection is spread is significant.”

This article first appeared on Medscape.com.

A small molecule can provide a “clinically meaningful reduction” in severe oral mucositis without affecting tumor control in head and neck cancer, according to an investigator from a phase 2 trial.

The molecule, GC4419 (avasopasem manganese), is designed to convert superoxide to hydrogen peroxide and oxygen, thereby protecting normal tissue from damage associated with radiotherapy.

Investigators tested GC4419 in a phase 2 trial of patients with locally advanced oral cavity or oropharynx cancer who received intensity-modulated radiotherapy plus cisplatin. Initial results from this trial were published in December (J Clin Oncol. 2019 Dec 1;37[34]:3256-65).

Carryn M. Anderson, MD, of University of Iowa Hospitals & Clinics in Iowa City, presented updated results at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

The trial (NCT02508389) enrolled 223 patients scheduled to be treated with intensity-modulated radiotherapy (60-72 Gy or greater than 50 Gy to more than two oral sites) plus cisplatin (weekly or every 3 weeks).

The patients were randomized to receive 30 mg of GC4419 (n = 73), 90 mg of GC4419 (n = 76), or placebo (n = 74) intravenously over 60 minutes prior to each radiotherapy fraction. Baseline patient and tumor characteristics were well balanced among the treatment arms.
 

Efficacy and safety

The study’s primary endpoint was the duration of severe oral mucositis. When compared with placebo, the 90-mg dose of GC4419 conferred a 92% reduction in median days of severe oral mucositis (P = .024).

The 90-mg dose of GC4419 also reduced the incidence of severe oral mucositis by 34% (P = .009) and the rate of grade 4 oral mucositis by 47% (P = .045) when compared with placebo.

“GC4419, particularly the 90-mg dosage, provides a clinically meaningful reduction in severe oral mucositis duration, incidence, and severity,” Dr. Anderson noted.

“Safety was comparable across study arms,” she added. “The most frequent adverse events were those already expected with cisplatin and radiation, and those were not worsened in any way by the addition of this drug.”

Adverse events expected with GC4419 were “mild and transient,” according to Dr. Anderson. These events included syncope, hypotension/orthostasis, and oral/facial paresthesia.

Grade 3 syncope occurred in 4% of patients in the placebo arm, 4% in the 30-mg arm, and 6% in the 90-mg arm. Grade 3 hypotension/orthostasis occurred in 6%, 4%, and 4%, respectively. Grade 1 oral/facial paresthesia occurred in 15%, 10%, and 19%, respectively.
 

Long-term outcomes

“The 1- and 2-year tumor control is similar with utilization of [GC4419], and this is consistent with the drug’s known mechanism and previous animal models,” Dr. Anderson said.

At 1 and 2 years, there were no significant differences between the treatment arms with regard to locoregional control, distant metastasis, progression-free survival, or overall survival.

The 1-year progression-free survival was 82% in the placebo arm, 86% in the 30-mg arm, and 80% in the 90-mg arm. The 1-year overall survival was 93%, 91%, and 88%, respectively.

The 2-year progression-free survival was 77% in the placebo arm, 76% in the 30-mg arm, and 77% in the 90-mg arm. The 1-year overall survival was 87%, 85%, and 86%, respectively.
 

From trials to practice

Despite the favorable results of this trial, meeting attendees expressed concerns that the administration of GC4419 may not be feasible in real-life because it is labor- and resource-intensive.

“Methodologically, the study was excellent,” said attendee Shahid Iqbal, MBBS, a consultant clinical oncologist at Newcastle upon Tyne Hospitals NHS Foundation Trust in the United Kingdom, who was not involved in this trial.

Dr. Iqbal noted that this placebo-controlled trial had a “very reasonable number of patients in each arm,” the 90-mg dose of GC4419 was “effective,” and the drug had “no adverse impact on survival.”

“However, in my personal opinion, this intravenous infusion on a daily basis is not feasible in real life,” Dr. Iqbal said. “I cannot see this becoming a standard of care in National Health Service UK. This is simply not cost-effective at all.”

Although she didn’t address costs, Dr. Anderson did acknowledge that administering GC4419 is labor intensive.

“But we are hopeful that, if this drug ultimately makes it to [Food and Drug Administration] approval, the efficacy benefits we are showing will make the work flow changes worthwhile,” she said. “We certainly have shown that, in this study, 44 institutions could make that happen. At the University of Iowa, we found it easiest to institute an infusion space within the department of radiation oncology rather than relying on our medical oncology colleagues to let us borrow a chair.”

GC4419 is now under investigation in a phase 3 trial (NCT03689712) and has received fast track and breakthrough therapy designations from the FDA.

The phase 2 trial was sponsored by Galera Therapeutics. Dr. Anderson is an uncompensated research adviser to the company. Dr. Iqbal has no relevant conflicts of interest.

[email protected]

SOURCE: Anderson CM et al. Head and Neck Cancer Symposium. Abstract LBA 2.

A small molecule can provide a “clinically meaningful reduction” in severe oral mucositis without affecting tumor control in head and neck cancer, according to an investigator from a phase 2 trial.

The molecule, GC4419 (avasopasem manganese), is designed to convert superoxide to hydrogen peroxide and oxygen, thereby protecting normal tissue from damage associated with radiotherapy.

Investigators tested GC4419 in a phase 2 trial of patients with locally advanced oral cavity or oropharynx cancer who received intensity-modulated radiotherapy plus cisplatin. Initial results from this trial were published in December (J Clin Oncol. 2019 Dec 1;37[34]:3256-65).

Carryn M. Anderson, MD, of University of Iowa Hospitals & Clinics in Iowa City, presented updated results at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

The trial (NCT02508389) enrolled 223 patients scheduled to be treated with intensity-modulated radiotherapy (60-72 Gy or greater than 50 Gy to more than two oral sites) plus cisplatin (weekly or every 3 weeks).

The patients were randomized to receive 30 mg of GC4419 (n = 73), 90 mg of GC4419 (n = 76), or placebo (n = 74) intravenously over 60 minutes prior to each radiotherapy fraction. Baseline patient and tumor characteristics were well balanced among the treatment arms.
 

Efficacy and safety

The study’s primary endpoint was the duration of severe oral mucositis. When compared with placebo, the 90-mg dose of GC4419 conferred a 92% reduction in median days of severe oral mucositis (P = .024).

The 90-mg dose of GC4419 also reduced the incidence of severe oral mucositis by 34% (P = .009) and the rate of grade 4 oral mucositis by 47% (P = .045) when compared with placebo.

“GC4419, particularly the 90-mg dosage, provides a clinically meaningful reduction in severe oral mucositis duration, incidence, and severity,” Dr. Anderson noted.

“Safety was comparable across study arms,” she added. “The most frequent adverse events were those already expected with cisplatin and radiation, and those were not worsened in any way by the addition of this drug.”

Adverse events expected with GC4419 were “mild and transient,” according to Dr. Anderson. These events included syncope, hypotension/orthostasis, and oral/facial paresthesia.

Grade 3 syncope occurred in 4% of patients in the placebo arm, 4% in the 30-mg arm, and 6% in the 90-mg arm. Grade 3 hypotension/orthostasis occurred in 6%, 4%, and 4%, respectively. Grade 1 oral/facial paresthesia occurred in 15%, 10%, and 19%, respectively.
 

Long-term outcomes

“The 1- and 2-year tumor control is similar with utilization of [GC4419], and this is consistent with the drug’s known mechanism and previous animal models,” Dr. Anderson said.

At 1 and 2 years, there were no significant differences between the treatment arms with regard to locoregional control, distant metastasis, progression-free survival, or overall survival.

The 1-year progression-free survival was 82% in the placebo arm, 86% in the 30-mg arm, and 80% in the 90-mg arm. The 1-year overall survival was 93%, 91%, and 88%, respectively.

The 2-year progression-free survival was 77% in the placebo arm, 76% in the 30-mg arm, and 77% in the 90-mg arm. The 1-year overall survival was 87%, 85%, and 86%, respectively.
 

From trials to practice

Despite the favorable results of this trial, meeting attendees expressed concerns that the administration of GC4419 may not be feasible in real-life because it is labor- and resource-intensive.

“Methodologically, the study was excellent,” said attendee Shahid Iqbal, MBBS, a consultant clinical oncologist at Newcastle upon Tyne Hospitals NHS Foundation Trust in the United Kingdom, who was not involved in this trial.

Dr. Iqbal noted that this placebo-controlled trial had a “very reasonable number of patients in each arm,” the 90-mg dose of GC4419 was “effective,” and the drug had “no adverse impact on survival.”

“However, in my personal opinion, this intravenous infusion on a daily basis is not feasible in real life,” Dr. Iqbal said. “I cannot see this becoming a standard of care in National Health Service UK. This is simply not cost-effective at all.”

Although she didn’t address costs, Dr. Anderson did acknowledge that administering GC4419 is labor intensive.

“But we are hopeful that, if this drug ultimately makes it to [Food and Drug Administration] approval, the efficacy benefits we are showing will make the work flow changes worthwhile,” she said. “We certainly have shown that, in this study, 44 institutions could make that happen. At the University of Iowa, we found it easiest to institute an infusion space within the department of radiation oncology rather than relying on our medical oncology colleagues to let us borrow a chair.”

GC4419 is now under investigation in a phase 3 trial (NCT03689712) and has received fast track and breakthrough therapy designations from the FDA.

The phase 2 trial was sponsored by Galera Therapeutics. Dr. Anderson is an uncompensated research adviser to the company. Dr. Iqbal has no relevant conflicts of interest.

[email protected]

SOURCE: Anderson CM et al. Head and Neck Cancer Symposium. Abstract LBA 2.

A small molecule can provide a “clinically meaningful reduction” in severe oral mucositis without affecting tumor control in head and neck cancer, according to an investigator from a phase 2 trial.

The molecule, GC4419 (avasopasem manganese), is designed to convert superoxide to hydrogen peroxide and oxygen, thereby protecting normal tissue from damage associated with radiotherapy.

Investigators tested GC4419 in a phase 2 trial of patients with locally advanced oral cavity or oropharynx cancer who received intensity-modulated radiotherapy plus cisplatin. Initial results from this trial were published in December (J Clin Oncol. 2019 Dec 1;37[34]:3256-65).

Carryn M. Anderson, MD, of University of Iowa Hospitals & Clinics in Iowa City, presented updated results at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

The trial (NCT02508389) enrolled 223 patients scheduled to be treated with intensity-modulated radiotherapy (60-72 Gy or greater than 50 Gy to more than two oral sites) plus cisplatin (weekly or every 3 weeks).

The patients were randomized to receive 30 mg of GC4419 (n = 73), 90 mg of GC4419 (n = 76), or placebo (n = 74) intravenously over 60 minutes prior to each radiotherapy fraction. Baseline patient and tumor characteristics were well balanced among the treatment arms.
 

Efficacy and safety

The study’s primary endpoint was the duration of severe oral mucositis. When compared with placebo, the 90-mg dose of GC4419 conferred a 92% reduction in median days of severe oral mucositis (P = .024).

The 90-mg dose of GC4419 also reduced the incidence of severe oral mucositis by 34% (P = .009) and the rate of grade 4 oral mucositis by 47% (P = .045) when compared with placebo.

“GC4419, particularly the 90-mg dosage, provides a clinically meaningful reduction in severe oral mucositis duration, incidence, and severity,” Dr. Anderson noted.

“Safety was comparable across study arms,” she added. “The most frequent adverse events were those already expected with cisplatin and radiation, and those were not worsened in any way by the addition of this drug.”

Adverse events expected with GC4419 were “mild and transient,” according to Dr. Anderson. These events included syncope, hypotension/orthostasis, and oral/facial paresthesia.

Grade 3 syncope occurred in 4% of patients in the placebo arm, 4% in the 30-mg arm, and 6% in the 90-mg arm. Grade 3 hypotension/orthostasis occurred in 6%, 4%, and 4%, respectively. Grade 1 oral/facial paresthesia occurred in 15%, 10%, and 19%, respectively.
 

Long-term outcomes

“The 1- and 2-year tumor control is similar with utilization of [GC4419], and this is consistent with the drug’s known mechanism and previous animal models,” Dr. Anderson said.

At 1 and 2 years, there were no significant differences between the treatment arms with regard to locoregional control, distant metastasis, progression-free survival, or overall survival.

The 1-year progression-free survival was 82% in the placebo arm, 86% in the 30-mg arm, and 80% in the 90-mg arm. The 1-year overall survival was 93%, 91%, and 88%, respectively.

The 2-year progression-free survival was 77% in the placebo arm, 76% in the 30-mg arm, and 77% in the 90-mg arm. The 1-year overall survival was 87%, 85%, and 86%, respectively.
 

From trials to practice

Despite the favorable results of this trial, meeting attendees expressed concerns that the administration of GC4419 may not be feasible in real-life because it is labor- and resource-intensive.

“Methodologically, the study was excellent,” said attendee Shahid Iqbal, MBBS, a consultant clinical oncologist at Newcastle upon Tyne Hospitals NHS Foundation Trust in the United Kingdom, who was not involved in this trial.

Dr. Iqbal noted that this placebo-controlled trial had a “very reasonable number of patients in each arm,” the 90-mg dose of GC4419 was “effective,” and the drug had “no adverse impact on survival.”

“However, in my personal opinion, this intravenous infusion on a daily basis is not feasible in real life,” Dr. Iqbal said. “I cannot see this becoming a standard of care in National Health Service UK. This is simply not cost-effective at all.”

Although she didn’t address costs, Dr. Anderson did acknowledge that administering GC4419 is labor intensive.

“But we are hopeful that, if this drug ultimately makes it to [Food and Drug Administration] approval, the efficacy benefits we are showing will make the work flow changes worthwhile,” she said. “We certainly have shown that, in this study, 44 institutions could make that happen. At the University of Iowa, we found it easiest to institute an infusion space within the department of radiation oncology rather than relying on our medical oncology colleagues to let us borrow a chair.”

GC4419 is now under investigation in a phase 3 trial (NCT03689712) and has received fast track and breakthrough therapy designations from the FDA.

The phase 2 trial was sponsored by Galera Therapeutics. Dr. Anderson is an uncompensated research adviser to the company. Dr. Iqbal has no relevant conflicts of interest.

[email protected]

SOURCE: Anderson CM et al. Head and Neck Cancer Symposium. Abstract LBA 2.

The combination of radiotherapy plus pembrolizumab (Keytruda, Merck) leads to good disease control in recurrent or metastatic head and neck squamous cell cancer (HNSCC) in patients for whom cisplatin would prove to be too toxic, a phase 2 trial suggests.

“There are convincing arguments that radiation sensitizes patients to immunotherapy and can enhance its effects,” Jared Weiss, MD, associate professor of medicine, UNC Lineberger Comprehensive Cancer, Chapel Hill, North Carolina, said in a statement.

“And the opposite direction also seems to be true – radiation therapy needs a functional immune system to work. Our hope was that pembrolizumab might be a radiation sensitizer for these patients,” he said.

The study was presented at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

Both modalities have had some outstanding results in the past, observed Weiss. “If you look back to the historic studies, radiation alone often cures patients with this disease, while some of the first patients treated with pembrolizumab for recurrent/metastatic cancer are still alive many years out, with no evidence of disease,” he said.

“Our concept was that, in addition to whatever synergy the immunotherapy might provide with radiation, we also conceived of it as a ‘second shot on goal’ towards a cure, because there is durable control with drug alone,” he added.

Single-arm trial

The single-arm trial included 29 patients with locally advanced HNSCC.

Only about 10% of patients were current smokers, but more than half of the study group had a history of smoking. Of those, more than 55% had a history of 10 pack-years or more.

In slightly more than one third of patients, the primary site of the cancer was the base of the tongue. The tonsils were the primary site in slightly more than one third.

Platinum ineligibility was defined by provider and standard measures.

More than two thirds of patients were ineligible to receive cisplatin because of preexisting otopathy, including hearing impairment and tinnitus.

The combination of cisplatin and definitive-dose radiotherapy is standard treatment for locally advanced head and neck cancer, but contraindications to cisplatin are common in everyday clinical practice. Weiss noted that contraindications are present in about one third of his patients.

“We replaced standard, every-3-week cisplatin with pembrolizumab every 3 weeks,” Weiss explained, “and we hypothesized that with the ongoing effects of radiation therapy after completion, that additional adjuvant cycles could further sensitize patients [to the effects of radiation] without impairing recovery, so we added three adjuvant cycles as well,” he added.

With six cycles of an every-3-week drug, patients received 18 weeks of pembrolizumab in total.

Echoing results from the previously reported KEYNOTE-48 trial, pembrolizumab given with radiotherapy instead of chemotherapy led to an overall progression-free survival (PFS) rate of 76% at 1 year and an estimated PFS of 71% at 2 years.

At 1 year, 86% of patients were still alive, and at 2 years, an estimated 75% of patients were still alive, Weiss added.

For patients with human papillomavirus 16–positive cancer, rates of PFS and overall survival were slightly better, at 88% and 94%, respectively.

With regard to toxicities, “For the most part, this [treatment regimen] looks like radiation alone with one very notable exception, which was lymphopenia,” Weiss observed. Grade 3-4 lymphopenia affected 59% of patients.

Lymphocyte count hit bottom at week 4, he added, with only partial recovery at week 20 and no further recovery at 40 weeks. Lymphocyte count alone or any change in it was not predictive of early progression.

However, in comparing patients who experienced early disease progression to patients who did not experience progression, levels of baseline naive B cells in peripheral blood were higher and levels of circulating marginal zone B cells were lower in patients with progressive disease, Weiss reported.

Patient-reported outcomes indicated that common symptoms of treatment peaked at week 10, and there was relative recovery by week 20.

As reflected by Functional Assessment of Cancer Therapy (FACT) scores, which include social, emotional, and functional well-being, as well as the head and neck cancer scale, “we again see a nadir at 10 weeks with relative recovery at 20 weeks,” Weiss noted.

“We found that concurrent pembrolizumab with radiotherapy is a safe and feasible option for locally advanced head and neck cancer patients with cisplatin ineligibility,” Weiss concluded.

More research is being conducted in this area, and multiple ongoing studies will further elucidate the value of PD-1 or PD-L1 checkpoint blockade with definitive radiation therapy, he added.

The study was funded by Merck & Co. Weiss’ institution has received research funding from Celgene, Pfizer, Merck, AZ/Medimmmune, Amgen, Carefusion, G1 Therapeutics, Immunicum, Loxo/Lilly, and the Jimmy V Foundation. Weiss has received honoraria for consulting from AstraZeneca, EMD Serono, Genentech, Inivata, Celgene, G1 Therapeutics, Jounce Therapeutics, Abbvie, Rakuten, Nanobiotix, Azitra, Loxo/Lilly, Pfizer, and Blueprint had has stock in Nektar and Vesselon.

This article first appeared on Medscape.com.

The combination of radiotherapy plus pembrolizumab (Keytruda, Merck) leads to good disease control in recurrent or metastatic head and neck squamous cell cancer (HNSCC) in patients for whom cisplatin would prove to be too toxic, a phase 2 trial suggests.

“There are convincing arguments that radiation sensitizes patients to immunotherapy and can enhance its effects,” Jared Weiss, MD, associate professor of medicine, UNC Lineberger Comprehensive Cancer, Chapel Hill, North Carolina, said in a statement.

“And the opposite direction also seems to be true – radiation therapy needs a functional immune system to work. Our hope was that pembrolizumab might be a radiation sensitizer for these patients,” he said.

The study was presented at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

Both modalities have had some outstanding results in the past, observed Weiss. “If you look back to the historic studies, radiation alone often cures patients with this disease, while some of the first patients treated with pembrolizumab for recurrent/metastatic cancer are still alive many years out, with no evidence of disease,” he said.

“Our concept was that, in addition to whatever synergy the immunotherapy might provide with radiation, we also conceived of it as a ‘second shot on goal’ towards a cure, because there is durable control with drug alone,” he added.

Single-arm trial

The single-arm trial included 29 patients with locally advanced HNSCC.

Only about 10% of patients were current smokers, but more than half of the study group had a history of smoking. Of those, more than 55% had a history of 10 pack-years or more.

In slightly more than one third of patients, the primary site of the cancer was the base of the tongue. The tonsils were the primary site in slightly more than one third.

Platinum ineligibility was defined by provider and standard measures.

More than two thirds of patients were ineligible to receive cisplatin because of preexisting otopathy, including hearing impairment and tinnitus.

The combination of cisplatin and definitive-dose radiotherapy is standard treatment for locally advanced head and neck cancer, but contraindications to cisplatin are common in everyday clinical practice. Weiss noted that contraindications are present in about one third of his patients.

“We replaced standard, every-3-week cisplatin with pembrolizumab every 3 weeks,” Weiss explained, “and we hypothesized that with the ongoing effects of radiation therapy after completion, that additional adjuvant cycles could further sensitize patients [to the effects of radiation] without impairing recovery, so we added three adjuvant cycles as well,” he added.

With six cycles of an every-3-week drug, patients received 18 weeks of pembrolizumab in total.

Echoing results from the previously reported KEYNOTE-48 trial, pembrolizumab given with radiotherapy instead of chemotherapy led to an overall progression-free survival (PFS) rate of 76% at 1 year and an estimated PFS of 71% at 2 years.

At 1 year, 86% of patients were still alive, and at 2 years, an estimated 75% of patients were still alive, Weiss added.

For patients with human papillomavirus 16–positive cancer, rates of PFS and overall survival were slightly better, at 88% and 94%, respectively.

With regard to toxicities, “For the most part, this [treatment regimen] looks like radiation alone with one very notable exception, which was lymphopenia,” Weiss observed. Grade 3-4 lymphopenia affected 59% of patients.

Lymphocyte count hit bottom at week 4, he added, with only partial recovery at week 20 and no further recovery at 40 weeks. Lymphocyte count alone or any change in it was not predictive of early progression.

However, in comparing patients who experienced early disease progression to patients who did not experience progression, levels of baseline naive B cells in peripheral blood were higher and levels of circulating marginal zone B cells were lower in patients with progressive disease, Weiss reported.

Patient-reported outcomes indicated that common symptoms of treatment peaked at week 10, and there was relative recovery by week 20.

As reflected by Functional Assessment of Cancer Therapy (FACT) scores, which include social, emotional, and functional well-being, as well as the head and neck cancer scale, “we again see a nadir at 10 weeks with relative recovery at 20 weeks,” Weiss noted.

“We found that concurrent pembrolizumab with radiotherapy is a safe and feasible option for locally advanced head and neck cancer patients with cisplatin ineligibility,” Weiss concluded.

More research is being conducted in this area, and multiple ongoing studies will further elucidate the value of PD-1 or PD-L1 checkpoint blockade with definitive radiation therapy, he added.

The study was funded by Merck & Co. Weiss’ institution has received research funding from Celgene, Pfizer, Merck, AZ/Medimmmune, Amgen, Carefusion, G1 Therapeutics, Immunicum, Loxo/Lilly, and the Jimmy V Foundation. Weiss has received honoraria for consulting from AstraZeneca, EMD Serono, Genentech, Inivata, Celgene, G1 Therapeutics, Jounce Therapeutics, Abbvie, Rakuten, Nanobiotix, Azitra, Loxo/Lilly, Pfizer, and Blueprint had has stock in Nektar and Vesselon.

This article first appeared on Medscape.com.

The combination of radiotherapy plus pembrolizumab (Keytruda, Merck) leads to good disease control in recurrent or metastatic head and neck squamous cell cancer (HNSCC) in patients for whom cisplatin would prove to be too toxic, a phase 2 trial suggests.

“There are convincing arguments that radiation sensitizes patients to immunotherapy and can enhance its effects,” Jared Weiss, MD, associate professor of medicine, UNC Lineberger Comprehensive Cancer, Chapel Hill, North Carolina, said in a statement.

“And the opposite direction also seems to be true – radiation therapy needs a functional immune system to work. Our hope was that pembrolizumab might be a radiation sensitizer for these patients,” he said.

The study was presented at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

Both modalities have had some outstanding results in the past, observed Weiss. “If you look back to the historic studies, radiation alone often cures patients with this disease, while some of the first patients treated with pembrolizumab for recurrent/metastatic cancer are still alive many years out, with no evidence of disease,” he said.

“Our concept was that, in addition to whatever synergy the immunotherapy might provide with radiation, we also conceived of it as a ‘second shot on goal’ towards a cure, because there is durable control with drug alone,” he added.

Single-arm trial

The single-arm trial included 29 patients with locally advanced HNSCC.

Only about 10% of patients were current smokers, but more than half of the study group had a history of smoking. Of those, more than 55% had a history of 10 pack-years or more.

In slightly more than one third of patients, the primary site of the cancer was the base of the tongue. The tonsils were the primary site in slightly more than one third.

Platinum ineligibility was defined by provider and standard measures.

More than two thirds of patients were ineligible to receive cisplatin because of preexisting otopathy, including hearing impairment and tinnitus.

The combination of cisplatin and definitive-dose radiotherapy is standard treatment for locally advanced head and neck cancer, but contraindications to cisplatin are common in everyday clinical practice. Weiss noted that contraindications are present in about one third of his patients.

“We replaced standard, every-3-week cisplatin with pembrolizumab every 3 weeks,” Weiss explained, “and we hypothesized that with the ongoing effects of radiation therapy after completion, that additional adjuvant cycles could further sensitize patients [to the effects of radiation] without impairing recovery, so we added three adjuvant cycles as well,” he added.

With six cycles of an every-3-week drug, patients received 18 weeks of pembrolizumab in total.

Echoing results from the previously reported KEYNOTE-48 trial, pembrolizumab given with radiotherapy instead of chemotherapy led to an overall progression-free survival (PFS) rate of 76% at 1 year and an estimated PFS of 71% at 2 years.

At 1 year, 86% of patients were still alive, and at 2 years, an estimated 75% of patients were still alive, Weiss added.

For patients with human papillomavirus 16–positive cancer, rates of PFS and overall survival were slightly better, at 88% and 94%, respectively.

With regard to toxicities, “For the most part, this [treatment regimen] looks like radiation alone with one very notable exception, which was lymphopenia,” Weiss observed. Grade 3-4 lymphopenia affected 59% of patients.

Lymphocyte count hit bottom at week 4, he added, with only partial recovery at week 20 and no further recovery at 40 weeks. Lymphocyte count alone or any change in it was not predictive of early progression.

However, in comparing patients who experienced early disease progression to patients who did not experience progression, levels of baseline naive B cells in peripheral blood were higher and levels of circulating marginal zone B cells were lower in patients with progressive disease, Weiss reported.

Patient-reported outcomes indicated that common symptoms of treatment peaked at week 10, and there was relative recovery by week 20.

As reflected by Functional Assessment of Cancer Therapy (FACT) scores, which include social, emotional, and functional well-being, as well as the head and neck cancer scale, “we again see a nadir at 10 weeks with relative recovery at 20 weeks,” Weiss noted.

“We found that concurrent pembrolizumab with radiotherapy is a safe and feasible option for locally advanced head and neck cancer patients with cisplatin ineligibility,” Weiss concluded.

More research is being conducted in this area, and multiple ongoing studies will further elucidate the value of PD-1 or PD-L1 checkpoint blockade with definitive radiation therapy, he added.

The study was funded by Merck & Co. Weiss’ institution has received research funding from Celgene, Pfizer, Merck, AZ/Medimmmune, Amgen, Carefusion, G1 Therapeutics, Immunicum, Loxo/Lilly, and the Jimmy V Foundation. Weiss has received honoraria for consulting from AstraZeneca, EMD Serono, Genentech, Inivata, Celgene, G1 Therapeutics, Jounce Therapeutics, Abbvie, Rakuten, Nanobiotix, Azitra, Loxo/Lilly, Pfizer, and Blueprint had has stock in Nektar and Vesselon.

This article first appeared on Medscape.com.

Everolimus, a safe, cheap and well-tolerated drug, prolonged progression-free survival (PFS) compared with placebo during the year patients with advanced head and neck squamous cell carcinoma (HNSCC) were on it, a phase 2 study indicates.

Advanced HNSCC

The investigator-initiated trial randomly assigned 28 patients with advanced HNSCC to everolimus 10 mg orally once daily or placebo for a maximum of 1 year or until disease progression, whichever came first.

Patients had stage IV HNSCC but had to be disease-free clinically and radiologically following definitive treatment with chemoradiation or surgery followed by chemoradiation. There was no difference in the type of definitive treatment received prior to the intervention between the two groups.

Adjuvant therapy was initiated between 8 and 16 weeks after completing definitive therapy.

If patients had HPV-positive oropharyngeal cancer, they had to have a minimum of 10 pack-years of smoking history.

“The primary endpoint was PFS at 2 years; the secondary endpoint was toxicity,” Nathan observed.

Oral mucositis and leukopenia were common but only 7% of patients developed grade 3 mucositis or leukopenia.

Other grade 3 or greater toxicities were reported in 16 patients and were similar to the adverse events (AEs) noted in other trials with everolimus. Only two patients developed serious AEs possibly related to the drug.

At 1 year, 81% of patients on everolimus were disease-free compared with 57% of patients on placebo (P = .04), Nathan reported.

However, at 2 years, PFS – although continuing to favor those treated with adjuvant therapy – was no longer significant even though it was clear that during the year patients were receiving treatment, “there was a consistent, protective effect of everolimus,” Nathan suggested.
 

Special effect among TP53-mutated patients?

Targeted exon sequencing was also carried out, the results from which showed that TP53 was the most commonly mutated gene.

“As expected, HPV-negative tumors were more likely to be mutated for TP53,” Nathan observed. Approximately 80% of HPV-negative smoking-related HNSCC tumors carry the TP53 mutation.

Interestingly, survival rates were significantly higher in TP53-mutated patients treated with everolimus: 70% of the patients were still alive at 2 years compared with only 22% of placebo controls (P = .026), she said.

This is a surprising finding, Nathan suggested, as patients with TP53 mutations traditionally have worse survival than those without, suggesting that these patients in particular appear to benefit from adjuvant everolimus.

“Everolimus is used for patients with breast cancer or renal cell cancer for extended periods without major side effects and there is potential for patients with TP53-mutated head and neck disease to see a survival benefit as well,” Nathan speculated.

However, additional trials are needed to confirm the link between the TP53 mutation and survival and to assess the safety of keeping patients with HNSCC on an mTOR inhibitor for longer than 1 year.

The study was funded by Novartis. Nathan has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Everolimus, a safe, cheap and well-tolerated drug, prolonged progression-free survival (PFS) compared with placebo during the year patients with advanced head and neck squamous cell carcinoma (HNSCC) were on it, a phase 2 study indicates.

Advanced HNSCC

The investigator-initiated trial randomly assigned 28 patients with advanced HNSCC to everolimus 10 mg orally once daily or placebo for a maximum of 1 year or until disease progression, whichever came first.

Patients had stage IV HNSCC but had to be disease-free clinically and radiologically following definitive treatment with chemoradiation or surgery followed by chemoradiation. There was no difference in the type of definitive treatment received prior to the intervention between the two groups.

Adjuvant therapy was initiated between 8 and 16 weeks after completing definitive therapy.

If patients had HPV-positive oropharyngeal cancer, they had to have a minimum of 10 pack-years of smoking history.

“The primary endpoint was PFS at 2 years; the secondary endpoint was toxicity,” Nathan observed.

Oral mucositis and leukopenia were common but only 7% of patients developed grade 3 mucositis or leukopenia.

Other grade 3 or greater toxicities were reported in 16 patients and were similar to the adverse events (AEs) noted in other trials with everolimus. Only two patients developed serious AEs possibly related to the drug.

At 1 year, 81% of patients on everolimus were disease-free compared with 57% of patients on placebo (P = .04), Nathan reported.

However, at 2 years, PFS – although continuing to favor those treated with adjuvant therapy – was no longer significant even though it was clear that during the year patients were receiving treatment, “there was a consistent, protective effect of everolimus,” Nathan suggested.
 

Special effect among TP53-mutated patients?

Targeted exon sequencing was also carried out, the results from which showed that TP53 was the most commonly mutated gene.

“As expected, HPV-negative tumors were more likely to be mutated for TP53,” Nathan observed. Approximately 80% of HPV-negative smoking-related HNSCC tumors carry the TP53 mutation.

Interestingly, survival rates were significantly higher in TP53-mutated patients treated with everolimus: 70% of the patients were still alive at 2 years compared with only 22% of placebo controls (P = .026), she said.

This is a surprising finding, Nathan suggested, as patients with TP53 mutations traditionally have worse survival than those without, suggesting that these patients in particular appear to benefit from adjuvant everolimus.

“Everolimus is used for patients with breast cancer or renal cell cancer for extended periods without major side effects and there is potential for patients with TP53-mutated head and neck disease to see a survival benefit as well,” Nathan speculated.

However, additional trials are needed to confirm the link between the TP53 mutation and survival and to assess the safety of keeping patients with HNSCC on an mTOR inhibitor for longer than 1 year.

The study was funded by Novartis. Nathan has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Everolimus, a safe, cheap and well-tolerated drug, prolonged progression-free survival (PFS) compared with placebo during the year patients with advanced head and neck squamous cell carcinoma (HNSCC) were on it, a phase 2 study indicates.

Advanced HNSCC

The investigator-initiated trial randomly assigned 28 patients with advanced HNSCC to everolimus 10 mg orally once daily or placebo for a maximum of 1 year or until disease progression, whichever came first.

Patients had stage IV HNSCC but had to be disease-free clinically and radiologically following definitive treatment with chemoradiation or surgery followed by chemoradiation. There was no difference in the type of definitive treatment received prior to the intervention between the two groups.

Adjuvant therapy was initiated between 8 and 16 weeks after completing definitive therapy.

If patients had HPV-positive oropharyngeal cancer, they had to have a minimum of 10 pack-years of smoking history.

“The primary endpoint was PFS at 2 years; the secondary endpoint was toxicity,” Nathan observed.

Oral mucositis and leukopenia were common but only 7% of patients developed grade 3 mucositis or leukopenia.

Other grade 3 or greater toxicities were reported in 16 patients and were similar to the adverse events (AEs) noted in other trials with everolimus. Only two patients developed serious AEs possibly related to the drug.

At 1 year, 81% of patients on everolimus were disease-free compared with 57% of patients on placebo (P = .04), Nathan reported.

However, at 2 years, PFS – although continuing to favor those treated with adjuvant therapy – was no longer significant even though it was clear that during the year patients were receiving treatment, “there was a consistent, protective effect of everolimus,” Nathan suggested.
 

Special effect among TP53-mutated patients?

Targeted exon sequencing was also carried out, the results from which showed that TP53 was the most commonly mutated gene.

“As expected, HPV-negative tumors were more likely to be mutated for TP53,” Nathan observed. Approximately 80% of HPV-negative smoking-related HNSCC tumors carry the TP53 mutation.

Interestingly, survival rates were significantly higher in TP53-mutated patients treated with everolimus: 70% of the patients were still alive at 2 years compared with only 22% of placebo controls (P = .026), she said.

This is a surprising finding, Nathan suggested, as patients with TP53 mutations traditionally have worse survival than those without, suggesting that these patients in particular appear to benefit from adjuvant everolimus.

“Everolimus is used for patients with breast cancer or renal cell cancer for extended periods without major side effects and there is potential for patients with TP53-mutated head and neck disease to see a survival benefit as well,” Nathan speculated.

However, additional trials are needed to confirm the link between the TP53 mutation and survival and to assess the safety of keeping patients with HNSCC on an mTOR inhibitor for longer than 1 year.

The study was funded by Novartis. Nathan has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Adding cetuximab to radiotherapy and cisplatin does not improve outcomes in patients with locoregionally advanced head and neck carcinoma, according to 10-year follow-up from a phase 3 trial.

The addition of cetuximab did not reduce local-regional failure or distant metastasis, and it did not improve progression-free or overall survival.

“With a median follow-up of over 10 years, this updated report confirms the addition of cetuximab to radiation/cisplatin did not improve any measured outcome in the entire cohort or when stratifying by p16 status,” said Jimmy J. Caudell, MD, of Moffitt Cancer Center in Tampa, Fla.

Dr. Caudell presented this update at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

Dr. Caudell noted that cisplatin plus radiotherapy or cetuximab plus radiotherapy have been shown to improve overall survival in patients with locoregionally advanced head and neck carcinoma. Researchers conducted this phase 3 trial, RTOG 0522 (NCT00265941), to determine if adding cetuximab to radiotherapy and cisplatin would improve progression-free survival.

The trial included 891 evaluable patients with stage T2 N2a-3 M0 or T3-4 N0-3 M0 disease. They were randomized to receive radiotherapy and cisplatin without cetuximab (n = 447) or with cetuximab (n = 444). Most patients were assigned to intensity-modulated radiotherapy (86.8% in the radiotherapy/cisplatin arm and 89.2% in the cetuximab arm) rather than 3-D conformal radiotherapy (13.2% and 10.8%, respectively).

Baseline characteristics were balanced between the treatment arms. The median age was 57 years (range, 31-79 years) in the radiotherapy/cisplatin arm and 58 years (range, 34-76 years) in the cetuximab arm. Nearly 90% of patients in both arms were men, and the oropharynx was the primary site of disease in about 70% of patients in both arms.

More patients were p16-positive (35.7% in the radiotherapy/cisplatin arm and 39.4% in the cetuximab arm) than were p16-negative (14.4% and 13.1%, respectively). However, p16 status was unknown for about half of patients in each arm.
 

Long-term efficacy

At a median follow-up of 10.1 years, 452 patients were still alive.

The rate of local-regional failure was 28.5% in the radiotherapy/cisplatin arm and 34.8% in the cetuximab arm (hazard ratio, 1.21; P = .94). The rate of distant metastases was 15% and 11.8%, respectively (HR, 0.79; P = .10).

The 10-year progression-free survival rate was 43.6% in the radiotherapy/cisplatin arm and 40.2% in the cetuximab arm (HR, 1.06; P = .74). The 10-year overall survival rate was 49.9% and 50%, respectively (HR, 0.97; P = .36)

“As might be expected, patients who were p16-positive had a substantially improved progression-free survival as well as overall survival,” Dr. Caudell said. “Patients who had p16-negative oropharyngeal cancer or nonoropharyngeal cancer had equivalent progression-free survival and overall survival.”

However, the addition of cetuximab did not improve progression-free or overall survival in patients with p16-positive, p16-negative oropharyngeal, or nonoropharyngeal cancers.

“[These results] have proven conclusively that the addition of cetuximab to concurrent cisplatin and radiation therapy does not improve outcomes in stage III-IV head and neck cancer, regardless of the primary tumor site and p16 status,” said Kartik Sehgal, MD, of Beth Israel Deaconess Medical Center in Boston, who was not involved in this study.
 

Late toxicity

Dr. Caudell noted that late toxicity was “substantial” in both treatment arms. Late toxicity was defined as adverse events occurring greater than 90 days from the start of radiotherapy.

The incidence of grade 3/4 late toxicity was 57.4% in the radiotherapy/cisplatin arm and 61.3% in the cetuximab arm (P = .26). The most common grade 3/4 late adverse event was dysphagia, occurring in 39.6% of patients in the radiotherapy/cisplatin arm and 38.2% of those in the cetuximab arm.

Other late grade 3/4 events (in the radiotherapy/cisplatin and cetuximab arms, respectively) included dry mouth (3% and 5%), radiation mucositis (5.3% and 7%), weight decrease (7.6% and 8.7%), hearing impairment (6% and 5%), pharynx mucositis/stomatitis (4.9% and 6%), and osteonecrosis (6% and 4.8%).

Feeding tube use was similar in both treatment arms over time. At 10 years, 14.3% of patients in the radiotherapy/cisplatin arm and 11% of those in the cetuximab arm used a feeding tube (P = .53).

“Despite the use of intensity-modulated radiotherapy, there was a high incidence of late grade 3 and higher toxicities, primarily related to dysphagia, which have substantial effects on the quality of life of our patients,” Dr. Sehgal noted. “These findings need to be considered carefully while designing future studies.

“Future directions for the management of locoregionally advanced head and neck cancer include evaluation of benefits from the addition of immune checkpoint inhibitors to cisplatin with concurrent radiation therapy (e.g., JAVELIN with avelumab [NCT01772004], KEYNOTE-412 with pembrolizumab [NCT03040999], and NCT03349710 with nivolumab) and whether immune checkpoint inhibitors can substitute for cisplatin in those being treated concurrently with radiation therapy (e.g., REACH trial comparing avelumab, cetuximab, and radiation therapy versus cisplatin plus radiation therapy [NCT02999087]).”

The current study was sponsored by the Radiation Therapy Oncology Group, the National Cancer Institute, NRG Oncology, and Eli Lilly. Dr. Caudell disclosed grants and fees from Varian Medical Systems. Dr. Sehgal had no conflicts of interest to disclose.

[email protected]

SOURCE: Caudell J et al. Head and Neck Cancers Symposium 2020, Abstract 6.

Adding cetuximab to radiotherapy and cisplatin does not improve outcomes in patients with locoregionally advanced head and neck carcinoma, according to 10-year follow-up from a phase 3 trial.

The addition of cetuximab did not reduce local-regional failure or distant metastasis, and it did not improve progression-free or overall survival.

“With a median follow-up of over 10 years, this updated report confirms the addition of cetuximab to radiation/cisplatin did not improve any measured outcome in the entire cohort or when stratifying by p16 status,” said Jimmy J. Caudell, MD, of Moffitt Cancer Center in Tampa, Fla.

Dr. Caudell presented this update at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

Dr. Caudell noted that cisplatin plus radiotherapy or cetuximab plus radiotherapy have been shown to improve overall survival in patients with locoregionally advanced head and neck carcinoma. Researchers conducted this phase 3 trial, RTOG 0522 (NCT00265941), to determine if adding cetuximab to radiotherapy and cisplatin would improve progression-free survival.

The trial included 891 evaluable patients with stage T2 N2a-3 M0 or T3-4 N0-3 M0 disease. They were randomized to receive radiotherapy and cisplatin without cetuximab (n = 447) or with cetuximab (n = 444). Most patients were assigned to intensity-modulated radiotherapy (86.8% in the radiotherapy/cisplatin arm and 89.2% in the cetuximab arm) rather than 3-D conformal radiotherapy (13.2% and 10.8%, respectively).

Baseline characteristics were balanced between the treatment arms. The median age was 57 years (range, 31-79 years) in the radiotherapy/cisplatin arm and 58 years (range, 34-76 years) in the cetuximab arm. Nearly 90% of patients in both arms were men, and the oropharynx was the primary site of disease in about 70% of patients in both arms.

More patients were p16-positive (35.7% in the radiotherapy/cisplatin arm and 39.4% in the cetuximab arm) than were p16-negative (14.4% and 13.1%, respectively). However, p16 status was unknown for about half of patients in each arm.
 

Long-term efficacy

At a median follow-up of 10.1 years, 452 patients were still alive.

The rate of local-regional failure was 28.5% in the radiotherapy/cisplatin arm and 34.8% in the cetuximab arm (hazard ratio, 1.21; P = .94). The rate of distant metastases was 15% and 11.8%, respectively (HR, 0.79; P = .10).

The 10-year progression-free survival rate was 43.6% in the radiotherapy/cisplatin arm and 40.2% in the cetuximab arm (HR, 1.06; P = .74). The 10-year overall survival rate was 49.9% and 50%, respectively (HR, 0.97; P = .36)

“As might be expected, patients who were p16-positive had a substantially improved progression-free survival as well as overall survival,” Dr. Caudell said. “Patients who had p16-negative oropharyngeal cancer or nonoropharyngeal cancer had equivalent progression-free survival and overall survival.”

However, the addition of cetuximab did not improve progression-free or overall survival in patients with p16-positive, p16-negative oropharyngeal, or nonoropharyngeal cancers.

“[These results] have proven conclusively that the addition of cetuximab to concurrent cisplatin and radiation therapy does not improve outcomes in stage III-IV head and neck cancer, regardless of the primary tumor site and p16 status,” said Kartik Sehgal, MD, of Beth Israel Deaconess Medical Center in Boston, who was not involved in this study.
 

Late toxicity

Dr. Caudell noted that late toxicity was “substantial” in both treatment arms. Late toxicity was defined as adverse events occurring greater than 90 days from the start of radiotherapy.

The incidence of grade 3/4 late toxicity was 57.4% in the radiotherapy/cisplatin arm and 61.3% in the cetuximab arm (P = .26). The most common grade 3/4 late adverse event was dysphagia, occurring in 39.6% of patients in the radiotherapy/cisplatin arm and 38.2% of those in the cetuximab arm.

Other late grade 3/4 events (in the radiotherapy/cisplatin and cetuximab arms, respectively) included dry mouth (3% and 5%), radiation mucositis (5.3% and 7%), weight decrease (7.6% and 8.7%), hearing impairment (6% and 5%), pharynx mucositis/stomatitis (4.9% and 6%), and osteonecrosis (6% and 4.8%).

Feeding tube use was similar in both treatment arms over time. At 10 years, 14.3% of patients in the radiotherapy/cisplatin arm and 11% of those in the cetuximab arm used a feeding tube (P = .53).

“Despite the use of intensity-modulated radiotherapy, there was a high incidence of late grade 3 and higher toxicities, primarily related to dysphagia, which have substantial effects on the quality of life of our patients,” Dr. Sehgal noted. “These findings need to be considered carefully while designing future studies.

“Future directions for the management of locoregionally advanced head and neck cancer include evaluation of benefits from the addition of immune checkpoint inhibitors to cisplatin with concurrent radiation therapy (e.g., JAVELIN with avelumab [NCT01772004], KEYNOTE-412 with pembrolizumab [NCT03040999], and NCT03349710 with nivolumab) and whether immune checkpoint inhibitors can substitute for cisplatin in those being treated concurrently with radiation therapy (e.g., REACH trial comparing avelumab, cetuximab, and radiation therapy versus cisplatin plus radiation therapy [NCT02999087]).”

The current study was sponsored by the Radiation Therapy Oncology Group, the National Cancer Institute, NRG Oncology, and Eli Lilly. Dr. Caudell disclosed grants and fees from Varian Medical Systems. Dr. Sehgal had no conflicts of interest to disclose.

[email protected]

SOURCE: Caudell J et al. Head and Neck Cancers Symposium 2020, Abstract 6.

Adding cetuximab to radiotherapy and cisplatin does not improve outcomes in patients with locoregionally advanced head and neck carcinoma, according to 10-year follow-up from a phase 3 trial.

The addition of cetuximab did not reduce local-regional failure or distant metastasis, and it did not improve progression-free or overall survival.

“With a median follow-up of over 10 years, this updated report confirms the addition of cetuximab to radiation/cisplatin did not improve any measured outcome in the entire cohort or when stratifying by p16 status,” said Jimmy J. Caudell, MD, of Moffitt Cancer Center in Tampa, Fla.

Dr. Caudell presented this update at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

Dr. Caudell noted that cisplatin plus radiotherapy or cetuximab plus radiotherapy have been shown to improve overall survival in patients with locoregionally advanced head and neck carcinoma. Researchers conducted this phase 3 trial, RTOG 0522 (NCT00265941), to determine if adding cetuximab to radiotherapy and cisplatin would improve progression-free survival.

The trial included 891 evaluable patients with stage T2 N2a-3 M0 or T3-4 N0-3 M0 disease. They were randomized to receive radiotherapy and cisplatin without cetuximab (n = 447) or with cetuximab (n = 444). Most patients were assigned to intensity-modulated radiotherapy (86.8% in the radiotherapy/cisplatin arm and 89.2% in the cetuximab arm) rather than 3-D conformal radiotherapy (13.2% and 10.8%, respectively).

Baseline characteristics were balanced between the treatment arms. The median age was 57 years (range, 31-79 years) in the radiotherapy/cisplatin arm and 58 years (range, 34-76 years) in the cetuximab arm. Nearly 90% of patients in both arms were men, and the oropharynx was the primary site of disease in about 70% of patients in both arms.

More patients were p16-positive (35.7% in the radiotherapy/cisplatin arm and 39.4% in the cetuximab arm) than were p16-negative (14.4% and 13.1%, respectively). However, p16 status was unknown for about half of patients in each arm.
 

Long-term efficacy

At a median follow-up of 10.1 years, 452 patients were still alive.

The rate of local-regional failure was 28.5% in the radiotherapy/cisplatin arm and 34.8% in the cetuximab arm (hazard ratio, 1.21; P = .94). The rate of distant metastases was 15% and 11.8%, respectively (HR, 0.79; P = .10).

The 10-year progression-free survival rate was 43.6% in the radiotherapy/cisplatin arm and 40.2% in the cetuximab arm (HR, 1.06; P = .74). The 10-year overall survival rate was 49.9% and 50%, respectively (HR, 0.97; P = .36)

“As might be expected, patients who were p16-positive had a substantially improved progression-free survival as well as overall survival,” Dr. Caudell said. “Patients who had p16-negative oropharyngeal cancer or nonoropharyngeal cancer had equivalent progression-free survival and overall survival.”

However, the addition of cetuximab did not improve progression-free or overall survival in patients with p16-positive, p16-negative oropharyngeal, or nonoropharyngeal cancers.

“[These results] have proven conclusively that the addition of cetuximab to concurrent cisplatin and radiation therapy does not improve outcomes in stage III-IV head and neck cancer, regardless of the primary tumor site and p16 status,” said Kartik Sehgal, MD, of Beth Israel Deaconess Medical Center in Boston, who was not involved in this study.
 

Late toxicity

Dr. Caudell noted that late toxicity was “substantial” in both treatment arms. Late toxicity was defined as adverse events occurring greater than 90 days from the start of radiotherapy.

The incidence of grade 3/4 late toxicity was 57.4% in the radiotherapy/cisplatin arm and 61.3% in the cetuximab arm (P = .26). The most common grade 3/4 late adverse event was dysphagia, occurring in 39.6% of patients in the radiotherapy/cisplatin arm and 38.2% of those in the cetuximab arm.

Other late grade 3/4 events (in the radiotherapy/cisplatin and cetuximab arms, respectively) included dry mouth (3% and 5%), radiation mucositis (5.3% and 7%), weight decrease (7.6% and 8.7%), hearing impairment (6% and 5%), pharynx mucositis/stomatitis (4.9% and 6%), and osteonecrosis (6% and 4.8%).

Feeding tube use was similar in both treatment arms over time. At 10 years, 14.3% of patients in the radiotherapy/cisplatin arm and 11% of those in the cetuximab arm used a feeding tube (P = .53).

“Despite the use of intensity-modulated radiotherapy, there was a high incidence of late grade 3 and higher toxicities, primarily related to dysphagia, which have substantial effects on the quality of life of our patients,” Dr. Sehgal noted. “These findings need to be considered carefully while designing future studies.

“Future directions for the management of locoregionally advanced head and neck cancer include evaluation of benefits from the addition of immune checkpoint inhibitors to cisplatin with concurrent radiation therapy (e.g., JAVELIN with avelumab [NCT01772004], KEYNOTE-412 with pembrolizumab [NCT03040999], and NCT03349710 with nivolumab) and whether immune checkpoint inhibitors can substitute for cisplatin in those being treated concurrently with radiation therapy (e.g., REACH trial comparing avelumab, cetuximab, and radiation therapy versus cisplatin plus radiation therapy [NCT02999087]).”

The current study was sponsored by the Radiation Therapy Oncology Group, the National Cancer Institute, NRG Oncology, and Eli Lilly. Dr. Caudell disclosed grants and fees from Varian Medical Systems. Dr. Sehgal had no conflicts of interest to disclose.

[email protected]

SOURCE: Caudell J et al. Head and Neck Cancers Symposium 2020, Abstract 6.

Preoperative nivolumab, with or without ipilimumab, appeared safe and effective in a phase 2 trial of patients with oral cavity squamous cell carcinoma (OCSCC).

“We found that nivolumab, with or without ipilimumab, was feasible prior to surgery in patients with oral cavity cancers, with no delays in surgery observed,” said Jonathan D. Schoenfeld, MD, of the Dana-Farber/Brigham and Women’s Cancer Center in Boston.

“We did observe promising rates of volumetric and pathologic response, with near-complete and complete responses observed, particularly in the nivo-ipi arm.”

Dr. Schoenfeld presented these results at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

“The rationale behind evaluation of neoadjuvant immunotherapy is the potential of tumor downstaging, converting unresectable disease to resectable and inducing durable immunological memory as a result of exposure to the full breadth of tumor antigens preoperatively,” said Kartik Sehgal, MD, of Beth Israel Deaconess Medical Center in Boston, who was not involved in this study.

“This randomized, phase 2 window study ... found that treatment with two neoadjuvant cycles of nivolumab alone or along with ipilimumab during the first cycle was feasible from an adverse events perspective and led to volumetric responses in approximately 50% of patients.”
 

Patients and treatment

The trial (NCT02919683) enrolled 30 patients with OCSCC, but 1 patient was excluded due to metastases at baseline. Patients had T2 (n = 20) or greater (n = 9) disease at baseline, and 58% of patients (n = 17) had node-positive disease.

The patients were randomized to two cycles of nivolumab (3 mg/kg) or nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg with the first cycle). Patients underwent surgery 3-7 days after completing cycle 2.

In the nivolumab monotherapy arm (n = 14), the median age was 64.4 years (range, 39.1-81 years), and 71.4% of patients were men. Oral tongue was the primary tumor site in 50% of patients, and 50% of patients had stage IV disease.

In the nivolumab-ipilimumab arm (n = 15), the median age was 65.2 years (range, 32.5-78.4 years), and 53.3% of patients were men. Oral tongue was the primary tumor site in 60% of patients, and 73.3% of patients had stage IV disease.
 

Safety and tolerability

Six patients did not receive the full cycle 2 dose of immunotherapy, two in the nivolumab arm and four in the nivolumab-ipilimumab arm. This was most commonly due to an infusion reaction during cycle 2, Dr. Schoenfeld said.

There were no cases in which surgery was delayed. However, one patient did have surgery moved to an earlier date after cycle 1 because of concerns about progression.

There were three severe immune-related adverse events. In the nivolumab-ipilimumab arm, there was a case of grade 3 pneumonitis and a case of grade 3 colitis. Both of these events were reversible with treatment.

In the nivolumab monotherapy arm, one patient had grade 4 new-onset diabetes with diabetic ketoacidosis. This patient is still insulin dependent.

Perioperative adverse events in both arms included pulmonary embolism, postoperative hematoma, and flap failures (n = 2). One patient with flap failure also had a perioperative stroke, experienced progressive clinical decline, and ultimately died.
 

Response and survival

In the nivolumab monotherapy arm, 50% of patients (n = 7) had a volumetric response, and 8% (n = 1) had a pathologic complete response.

In the nivolumab-ipilimumab arm, 53% of patients (n = 8) had a volumetric response, and 20% (n = 3) had a pathologic complete response.

“In general, we found that our response metrics were concordant; that is, patients with volumetric responses tended more frequently to have pathologic responses,” Dr. Schoenfeld said. “There were a couple notable cases where there were volumetric increases and significant pathologic responses.”

To identify factors associated with response, Dr. Schoenfeld and colleagues performed correlative multiplex immunofluorescence on 21 patient specimens prior to treatment.

“We did not identify any differences in baseline levels of PD-L1 expression in tumor cells between the two arms,” Dr. Schoenfeld noted. “We found that CD4-positive T cells in the pretreatment specimens correlated with pathologic response [P = .016]. Interestingly, this association was only significant in patients treated with nivo-ipi [P = .008] but not nivolumab alone [P = .83].”

Ten patients went on to receive radiation, and nine received chemoradiation. One patient presented to the operating room but did not undergo surgery because he was thought to require total glossectomy. This patient received chemoradiotherapy, achieved a complete response, and is still disease free after more than 3 years of follow-up.

The median follow-up for the entire cohort was 14 months. At 12 months, the progression-free survival rate was 85%, and the overall survival rate was 89%.

Dr. Schoenfeld noted that this study was not powered to assess survival or to directly compare nivolumab monotherapy and nivolumab plus ipilimumab.
 

‘Encouraging’ results, but what’s next?

“We were very encouraged by the toxicity data ... [and] the impressive pathologic responses in both arms, but particularly in the nivo-ipi arm,” Dr. Schoenfeld said. “I think the real question is, ‘Does this translate into a significant progression-free or overall survival advantage?’ So I think that would be something worthy of further study.”

“These results are encouraging for management of patients with oral cavity cancers who remain at high risk for recurrence with the current standard of care but will need validation in larger prospective studies,” Dr. Sehgal noted. “Multiple clinical trials are currently ongoing to evaluate the role of neoadjuvant immunotherapy for disease-specific outcomes, notable being phase 2 NCT02296684 and phase 3 KEYNOTE-689 (NCT03765918) with pembrolizumab and phase 3 IMSTAR-HN (NCT03700905) with nivolumab alone or along with ipilimumab.”

The current study was funded by Bristol-Myers Squibb. Dr. Schoenfeld disclosed relationships with Bristol-Myers Squibb and other companies. Dr. Sehgal had no relevant conflicts to disclose.

[email protected]

SOURCE: Schoenfeld J et al. Head and Neck Cancers Symposium 2020, Abstract 1.

Preoperative nivolumab, with or without ipilimumab, appeared safe and effective in a phase 2 trial of patients with oral cavity squamous cell carcinoma (OCSCC).

“We found that nivolumab, with or without ipilimumab, was feasible prior to surgery in patients with oral cavity cancers, with no delays in surgery observed,” said Jonathan D. Schoenfeld, MD, of the Dana-Farber/Brigham and Women’s Cancer Center in Boston.

“We did observe promising rates of volumetric and pathologic response, with near-complete and complete responses observed, particularly in the nivo-ipi arm.”

Dr. Schoenfeld presented these results at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

“The rationale behind evaluation of neoadjuvant immunotherapy is the potential of tumor downstaging, converting unresectable disease to resectable and inducing durable immunological memory as a result of exposure to the full breadth of tumor antigens preoperatively,” said Kartik Sehgal, MD, of Beth Israel Deaconess Medical Center in Boston, who was not involved in this study.

“This randomized, phase 2 window study ... found that treatment with two neoadjuvant cycles of nivolumab alone or along with ipilimumab during the first cycle was feasible from an adverse events perspective and led to volumetric responses in approximately 50% of patients.”
 

Patients and treatment

The trial (NCT02919683) enrolled 30 patients with OCSCC, but 1 patient was excluded due to metastases at baseline. Patients had T2 (n = 20) or greater (n = 9) disease at baseline, and 58% of patients (n = 17) had node-positive disease.

The patients were randomized to two cycles of nivolumab (3 mg/kg) or nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg with the first cycle). Patients underwent surgery 3-7 days after completing cycle 2.

In the nivolumab monotherapy arm (n = 14), the median age was 64.4 years (range, 39.1-81 years), and 71.4% of patients were men. Oral tongue was the primary tumor site in 50% of patients, and 50% of patients had stage IV disease.

In the nivolumab-ipilimumab arm (n = 15), the median age was 65.2 years (range, 32.5-78.4 years), and 53.3% of patients were men. Oral tongue was the primary tumor site in 60% of patients, and 73.3% of patients had stage IV disease.
 

Safety and tolerability

Six patients did not receive the full cycle 2 dose of immunotherapy, two in the nivolumab arm and four in the nivolumab-ipilimumab arm. This was most commonly due to an infusion reaction during cycle 2, Dr. Schoenfeld said.

There were no cases in which surgery was delayed. However, one patient did have surgery moved to an earlier date after cycle 1 because of concerns about progression.

There were three severe immune-related adverse events. In the nivolumab-ipilimumab arm, there was a case of grade 3 pneumonitis and a case of grade 3 colitis. Both of these events were reversible with treatment.

In the nivolumab monotherapy arm, one patient had grade 4 new-onset diabetes with diabetic ketoacidosis. This patient is still insulin dependent.

Perioperative adverse events in both arms included pulmonary embolism, postoperative hematoma, and flap failures (n = 2). One patient with flap failure also had a perioperative stroke, experienced progressive clinical decline, and ultimately died.
 

Response and survival

In the nivolumab monotherapy arm, 50% of patients (n = 7) had a volumetric response, and 8% (n = 1) had a pathologic complete response.

In the nivolumab-ipilimumab arm, 53% of patients (n = 8) had a volumetric response, and 20% (n = 3) had a pathologic complete response.

“In general, we found that our response metrics were concordant; that is, patients with volumetric responses tended more frequently to have pathologic responses,” Dr. Schoenfeld said. “There were a couple notable cases where there were volumetric increases and significant pathologic responses.”

To identify factors associated with response, Dr. Schoenfeld and colleagues performed correlative multiplex immunofluorescence on 21 patient specimens prior to treatment.

“We did not identify any differences in baseline levels of PD-L1 expression in tumor cells between the two arms,” Dr. Schoenfeld noted. “We found that CD4-positive T cells in the pretreatment specimens correlated with pathologic response [P = .016]. Interestingly, this association was only significant in patients treated with nivo-ipi [P = .008] but not nivolumab alone [P = .83].”

Ten patients went on to receive radiation, and nine received chemoradiation. One patient presented to the operating room but did not undergo surgery because he was thought to require total glossectomy. This patient received chemoradiotherapy, achieved a complete response, and is still disease free after more than 3 years of follow-up.

The median follow-up for the entire cohort was 14 months. At 12 months, the progression-free survival rate was 85%, and the overall survival rate was 89%.

Dr. Schoenfeld noted that this study was not powered to assess survival or to directly compare nivolumab monotherapy and nivolumab plus ipilimumab.
 

‘Encouraging’ results, but what’s next?

“We were very encouraged by the toxicity data ... [and] the impressive pathologic responses in both arms, but particularly in the nivo-ipi arm,” Dr. Schoenfeld said. “I think the real question is, ‘Does this translate into a significant progression-free or overall survival advantage?’ So I think that would be something worthy of further study.”

“These results are encouraging for management of patients with oral cavity cancers who remain at high risk for recurrence with the current standard of care but will need validation in larger prospective studies,” Dr. Sehgal noted. “Multiple clinical trials are currently ongoing to evaluate the role of neoadjuvant immunotherapy for disease-specific outcomes, notable being phase 2 NCT02296684 and phase 3 KEYNOTE-689 (NCT03765918) with pembrolizumab and phase 3 IMSTAR-HN (NCT03700905) with nivolumab alone or along with ipilimumab.”

The current study was funded by Bristol-Myers Squibb. Dr. Schoenfeld disclosed relationships with Bristol-Myers Squibb and other companies. Dr. Sehgal had no relevant conflicts to disclose.

[email protected]

SOURCE: Schoenfeld J et al. Head and Neck Cancers Symposium 2020, Abstract 1.

Preoperative nivolumab, with or without ipilimumab, appeared safe and effective in a phase 2 trial of patients with oral cavity squamous cell carcinoma (OCSCC).

“We found that nivolumab, with or without ipilimumab, was feasible prior to surgery in patients with oral cavity cancers, with no delays in surgery observed,” said Jonathan D. Schoenfeld, MD, of the Dana-Farber/Brigham and Women’s Cancer Center in Boston.

“We did observe promising rates of volumetric and pathologic response, with near-complete and complete responses observed, particularly in the nivo-ipi arm.”

Dr. Schoenfeld presented these results at the Multidisciplinary Head and Neck Cancer Symposium, sponsored by the American Society for Radiation Oncology.

“The rationale behind evaluation of neoadjuvant immunotherapy is the potential of tumor downstaging, converting unresectable disease to resectable and inducing durable immunological memory as a result of exposure to the full breadth of tumor antigens preoperatively,” said Kartik Sehgal, MD, of Beth Israel Deaconess Medical Center in Boston, who was not involved in this study.

“This randomized, phase 2 window study ... found that treatment with two neoadjuvant cycles of nivolumab alone or along with ipilimumab during the first cycle was feasible from an adverse events perspective and led to volumetric responses in approximately 50% of patients.”
 

Patients and treatment

The trial (NCT02919683) enrolled 30 patients with OCSCC, but 1 patient was excluded due to metastases at baseline. Patients had T2 (n = 20) or greater (n = 9) disease at baseline, and 58% of patients (n = 17) had node-positive disease.

The patients were randomized to two cycles of nivolumab (3 mg/kg) or nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg with the first cycle). Patients underwent surgery 3-7 days after completing cycle 2.

In the nivolumab monotherapy arm (n = 14), the median age was 64.4 years (range, 39.1-81 years), and 71.4% of patients were men. Oral tongue was the primary tumor site in 50% of patients, and 50% of patients had stage IV disease.

In the nivolumab-ipilimumab arm (n = 15), the median age was 65.2 years (range, 32.5-78.4 years), and 53.3% of patients were men. Oral tongue was the primary tumor site in 60% of patients, and 73.3% of patients had stage IV disease.
 

Safety and tolerability

Six patients did not receive the full cycle 2 dose of immunotherapy, two in the nivolumab arm and four in the nivolumab-ipilimumab arm. This was most commonly due to an infusion reaction during cycle 2, Dr. Schoenfeld said.

There were no cases in which surgery was delayed. However, one patient did have surgery moved to an earlier date after cycle 1 because of concerns about progression.

There were three severe immune-related adverse events. In the nivolumab-ipilimumab arm, there was a case of grade 3 pneumonitis and a case of grade 3 colitis. Both of these events were reversible with treatment.

In the nivolumab monotherapy arm, one patient had grade 4 new-onset diabetes with diabetic ketoacidosis. This patient is still insulin dependent.

Perioperative adverse events in both arms included pulmonary embolism, postoperative hematoma, and flap failures (n = 2). One patient with flap failure also had a perioperative stroke, experienced progressive clinical decline, and ultimately died.
 

Response and survival

In the nivolumab monotherapy arm, 50% of patients (n = 7) had a volumetric response, and 8% (n = 1) had a pathologic complete response.

In the nivolumab-ipilimumab arm, 53% of patients (n = 8) had a volumetric response, and 20% (n = 3) had a pathologic complete response.

“In general, we found that our response metrics were concordant; that is, patients with volumetric responses tended more frequently to have pathologic responses,” Dr. Schoenfeld said. “There were a couple notable cases where there were volumetric increases and significant pathologic responses.”

To identify factors associated with response, Dr. Schoenfeld and colleagues performed correlative multiplex immunofluorescence on 21 patient specimens prior to treatment.

“We did not identify any differences in baseline levels of PD-L1 expression in tumor cells between the two arms,” Dr. Schoenfeld noted. “We found that CD4-positive T cells in the pretreatment specimens correlated with pathologic response [P = .016]. Interestingly, this association was only significant in patients treated with nivo-ipi [P = .008] but not nivolumab alone [P = .83].”

Ten patients went on to receive radiation, and nine received chemoradiation. One patient presented to the operating room but did not undergo surgery because he was thought to require total glossectomy. This patient received chemoradiotherapy, achieved a complete response, and is still disease free after more than 3 years of follow-up.

The median follow-up for the entire cohort was 14 months. At 12 months, the progression-free survival rate was 85%, and the overall survival rate was 89%.

Dr. Schoenfeld noted that this study was not powered to assess survival or to directly compare nivolumab monotherapy and nivolumab plus ipilimumab.
 

‘Encouraging’ results, but what’s next?

“We were very encouraged by the toxicity data ... [and] the impressive pathologic responses in both arms, but particularly in the nivo-ipi arm,” Dr. Schoenfeld said. “I think the real question is, ‘Does this translate into a significant progression-free or overall survival advantage?’ So I think that would be something worthy of further study.”

“These results are encouraging for management of patients with oral cavity cancers who remain at high risk for recurrence with the current standard of care but will need validation in larger prospective studies,” Dr. Sehgal noted. “Multiple clinical trials are currently ongoing to evaluate the role of neoadjuvant immunotherapy for disease-specific outcomes, notable being phase 2 NCT02296684 and phase 3 KEYNOTE-689 (NCT03765918) with pembrolizumab and phase 3 IMSTAR-HN (NCT03700905) with nivolumab alone or along with ipilimumab.”

The current study was funded by Bristol-Myers Squibb. Dr. Schoenfeld disclosed relationships with Bristol-Myers Squibb and other companies. Dr. Sehgal had no relevant conflicts to disclose.

[email protected]

SOURCE: Schoenfeld J et al. Head and Neck Cancers Symposium 2020, Abstract 1.

There is not enough evidence to suggest that radiofrequency radiation (RFR) associated with cell phone use causes cancer, according to a review by the Food and Drug Administration.

The FDA reviewed the published literature from 2008 to 2018 and concluded that the data don’t support any quantifiable adverse health risks from RFR. However, the evidence is not without limitations.

The FDA’s evaluation included evidence from in vivo animal studies from Jan. 1, 2008, to Aug. 1, 2018, and epidemiologic studies in humans from Jan. 1, 2008, to May 8, 2018. Both kinds of evidence had limitations, but neither produced strong indications of any causal risks from cell phone use.

The FDA noted that in vivo animal studies are limited by variability of methods and RFR exposure, which make comparisons of results difficult. These studies are also impacted by the indirect effects of temperature increases (the only currently established biological effect of RFR) and stress experienced by the animals, which make teasing out the direct effects of RFR difficult.

The FDA noted that strong epidemiologic studies can provide more relevant and accurate information than in vivo studies, but epidemiologic studies are not without limitations. For example, most have participants track and self-report their cell phone use. There’s also no way to directly track certain factors of RFR exposure, such as frequency, duration, or intensity.

Even with those caveats in mind, the FDA wrote that, “based on the studies that are described in detail in this report, there is insufficient evidence to support a causal association between RFR exposure and tumorigenesis. There is a lack of clear dose-response relationship, a lack of consistent findings or specificity, and a lack of biological mechanistic plausibility.”

The full review is available on the FDA website.

[email protected]

There is not enough evidence to suggest that radiofrequency radiation (RFR) associated with cell phone use causes cancer, according to a review by the Food and Drug Administration.

The FDA reviewed the published literature from 2008 to 2018 and concluded that the data don’t support any quantifiable adverse health risks from RFR. However, the evidence is not without limitations.

The FDA’s evaluation included evidence from in vivo animal studies from Jan. 1, 2008, to Aug. 1, 2018, and epidemiologic studies in humans from Jan. 1, 2008, to May 8, 2018. Both kinds of evidence had limitations, but neither produced strong indications of any causal risks from cell phone use.

The FDA noted that in vivo animal studies are limited by variability of methods and RFR exposure, which make comparisons of results difficult. These studies are also impacted by the indirect effects of temperature increases (the only currently established biological effect of RFR) and stress experienced by the animals, which make teasing out the direct effects of RFR difficult.

The FDA noted that strong epidemiologic studies can provide more relevant and accurate information than in vivo studies, but epidemiologic studies are not without limitations. For example, most have participants track and self-report their cell phone use. There’s also no way to directly track certain factors of RFR exposure, such as frequency, duration, or intensity.

Even with those caveats in mind, the FDA wrote that, “based on the studies that are described in detail in this report, there is insufficient evidence to support a causal association between RFR exposure and tumorigenesis. There is a lack of clear dose-response relationship, a lack of consistent findings or specificity, and a lack of biological mechanistic plausibility.”

The full review is available on the FDA website.

[email protected]

There is not enough evidence to suggest that radiofrequency radiation (RFR) associated with cell phone use causes cancer, according to a review by the Food and Drug Administration.

The FDA reviewed the published literature from 2008 to 2018 and concluded that the data don’t support any quantifiable adverse health risks from RFR. However, the evidence is not without limitations.

The FDA’s evaluation included evidence from in vivo animal studies from Jan. 1, 2008, to Aug. 1, 2018, and epidemiologic studies in humans from Jan. 1, 2008, to May 8, 2018. Both kinds of evidence had limitations, but neither produced strong indications of any causal risks from cell phone use.

The FDA noted that in vivo animal studies are limited by variability of methods and RFR exposure, which make comparisons of results difficult. These studies are also impacted by the indirect effects of temperature increases (the only currently established biological effect of RFR) and stress experienced by the animals, which make teasing out the direct effects of RFR difficult.

The FDA noted that strong epidemiologic studies can provide more relevant and accurate information than in vivo studies, but epidemiologic studies are not without limitations. For example, most have participants track and self-report their cell phone use. There’s also no way to directly track certain factors of RFR exposure, such as frequency, duration, or intensity.

Even with those caveats in mind, the FDA wrote that, “based on the studies that are described in detail in this report, there is insufficient evidence to support a causal association between RFR exposure and tumorigenesis. There is a lack of clear dose-response relationship, a lack of consistent findings or specificity, and a lack of biological mechanistic plausibility.”

The full review is available on the FDA website.

[email protected]