Lung Cancer

In its updated cancer prevention guidelines, the American Cancer Society now recommends that “it is best not to drink alcohol.”

Previously, ACS suggested that, for those who consume alcoholic beverages, intake should be no more than one drink per day for women or two per day for men. That recommendation is still in place, but is now accompanied by this new, stronger directive.

The revised guidelines also place more emphasis on reducing the consumption of processed and red meat and highly processed foods, and on increasing physical activity.

But importantly, there is also a call for action from public, private, and community organizations to work to together to increase access to affordable, nutritious foods and physical activity.

“Making healthy choices can be challenging for many, and there are strategies included in the guidelines that communities can undertake to help reduce barriers to eating well and physical activity,” said Laura Makaroff, DO, American Cancer Society senior vice president. “Individual choice is an important part of a healthy lifestyle, but having the right policies and environmental factors to break down these barriers is also important, and that is something that clinicians can support.”

The guidelines were published in CA: A Cancer Journal for Clinicians.

The link between cancer and lifestyle factors has long been established, and for the past 4 decades, both government and leading nonprofit health organizations, including the ACS and the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR), have released cancer prevention guidelines and recommendations that focus on managing weight, diet, physical activity, and alcohol consumption.

In 2012, the ACS issued guidelines on diet and physical activity, and their current guideline is largely based on the WCRF/AICR systematic reviews and Continuous Update Project reports, which were last updated in 2018. The ACS guidelines also incorporated systematic reviews conducted by the International Agency on Cancer Research (IARC) and the U.S. Department of Agriculture and the Department of Health and Human Services (USDA/HHS) and other analyses that were published since the WCRF/AICR recommendations were released.
 

Emphasis on three areas

The differences between the old guidelines and the update do not differ dramatically, but Makaroff highlighted a few areas that have increased emphasis.

Time spent being physically active is critical. The recommendation has changed to encourage adults to engage in 150-300 minutes (2.5-5 hours) of moderate-intensity physical activity, or 75-150 minutes (1.25-2.5 hours) of vigorous-intensity physical activity, or an equivalent combination, per week. Achieving or exceeding the upper limit of 300 minutes is optimal.

“That is more than what we have recommended in the past, along with the continued message that children and adolescents engage in at least 1 hour of moderate- or vigorous-intensity activity each day,” she told Medscape Medical News.

The ACS has also increased emphasis on reducing the consumption of processed and red meat. “This is part of a healthy eating pattern and making sure that people are eating food that is high in nutrients that help achieve and maintain a healthy body weight,” said Makaroff.

A healthy diet should include a variety of dark green, red, and orange vegetables; fiber-rich legumes; and fruits with a variety of colors and whole grains, according to the guidelines. Sugar-sweetened beverages, highly processed foods, and refined grain products should be limited or avoided.

The revised dietary recommendations reflect a shift from a “reductionist or nutrient-centric” approach to one that is more “holistic” and that focuses on dietary patterns. In contrast to a focus on individual nutrients and bioactive compounds, the new approach is more consistent with what and how people actually eat, ACS points out.

The third area that Makaroff highlighted is alcohol, where the recommendation is to avoid or limit consumption. “The current update says not to drink alcohol, which is in line with the scientific evidence, but for those people who choose to drink alcohol, to limit it to one drink per day for women and two drinks per day for men.”

Thus, the change here is that the previous guideline only recommended limiting alcohol consumption, while the update suggests that, optimally, it should be avoided completely.

The ACS has also called for community involvement to help implement these goals: “Public, private, and community organizations should work collaboratively at national, state, and local levels to develop, advocate for, and implement policy and environmental changes that increase access to affordable, nutritious foods; provide safe, enjoyable, and accessible opportunities for physical activity; and limit alcohol for all individuals.”
 

No smoking guns

Commenting on the guidelines, Steven K. Clinton, MD, PhD, associate director of the Center for Advanced Functional Foods Research and Entrepreneurship at the Ohio State University, Columbus, explained that he didn’t view the change in alcohol as that much of an evolution. “It’s been 8 years since they revised their overall guidelines, and during that time frame, there has been an enormous growth in the evidence that has been used by many organizations,” he said.

Clinton noted that the guidelines are consistent with the whole body of current scientific literature. “It’s very easy to go to the document and look for the ‘smoking gun’ – but the smoking gun is really not one thing,” he said. “It’s a pattern, and what dietitians and nutritionists are telling people is that you need to orchestrate a healthy lifestyle and diet, with a diet that has a foundation of fruits, vegetables, whole grains, and modest intake of refined grains and meat. You are orchestrating an entire pattern to get the maximum benefit.”

Makaroff is an employee of the ACS. Clinton has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

In its updated cancer prevention guidelines, the American Cancer Society now recommends that “it is best not to drink alcohol.”

Previously, ACS suggested that, for those who consume alcoholic beverages, intake should be no more than one drink per day for women or two per day for men. That recommendation is still in place, but is now accompanied by this new, stronger directive.

The revised guidelines also place more emphasis on reducing the consumption of processed and red meat and highly processed foods, and on increasing physical activity.

But importantly, there is also a call for action from public, private, and community organizations to work to together to increase access to affordable, nutritious foods and physical activity.

“Making healthy choices can be challenging for many, and there are strategies included in the guidelines that communities can undertake to help reduce barriers to eating well and physical activity,” said Laura Makaroff, DO, American Cancer Society senior vice president. “Individual choice is an important part of a healthy lifestyle, but having the right policies and environmental factors to break down these barriers is also important, and that is something that clinicians can support.”

The guidelines were published in CA: A Cancer Journal for Clinicians.

The link between cancer and lifestyle factors has long been established, and for the past 4 decades, both government and leading nonprofit health organizations, including the ACS and the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR), have released cancer prevention guidelines and recommendations that focus on managing weight, diet, physical activity, and alcohol consumption.

In 2012, the ACS issued guidelines on diet and physical activity, and their current guideline is largely based on the WCRF/AICR systematic reviews and Continuous Update Project reports, which were last updated in 2018. The ACS guidelines also incorporated systematic reviews conducted by the International Agency on Cancer Research (IARC) and the U.S. Department of Agriculture and the Department of Health and Human Services (USDA/HHS) and other analyses that were published since the WCRF/AICR recommendations were released.
 

Emphasis on three areas

The differences between the old guidelines and the update do not differ dramatically, but Makaroff highlighted a few areas that have increased emphasis.

Time spent being physically active is critical. The recommendation has changed to encourage adults to engage in 150-300 minutes (2.5-5 hours) of moderate-intensity physical activity, or 75-150 minutes (1.25-2.5 hours) of vigorous-intensity physical activity, or an equivalent combination, per week. Achieving or exceeding the upper limit of 300 minutes is optimal.

“That is more than what we have recommended in the past, along with the continued message that children and adolescents engage in at least 1 hour of moderate- or vigorous-intensity activity each day,” she told Medscape Medical News.

The ACS has also increased emphasis on reducing the consumption of processed and red meat. “This is part of a healthy eating pattern and making sure that people are eating food that is high in nutrients that help achieve and maintain a healthy body weight,” said Makaroff.

A healthy diet should include a variety of dark green, red, and orange vegetables; fiber-rich legumes; and fruits with a variety of colors and whole grains, according to the guidelines. Sugar-sweetened beverages, highly processed foods, and refined grain products should be limited or avoided.

The revised dietary recommendations reflect a shift from a “reductionist or nutrient-centric” approach to one that is more “holistic” and that focuses on dietary patterns. In contrast to a focus on individual nutrients and bioactive compounds, the new approach is more consistent with what and how people actually eat, ACS points out.

The third area that Makaroff highlighted is alcohol, where the recommendation is to avoid or limit consumption. “The current update says not to drink alcohol, which is in line with the scientific evidence, but for those people who choose to drink alcohol, to limit it to one drink per day for women and two drinks per day for men.”

Thus, the change here is that the previous guideline only recommended limiting alcohol consumption, while the update suggests that, optimally, it should be avoided completely.

The ACS has also called for community involvement to help implement these goals: “Public, private, and community organizations should work collaboratively at national, state, and local levels to develop, advocate for, and implement policy and environmental changes that increase access to affordable, nutritious foods; provide safe, enjoyable, and accessible opportunities for physical activity; and limit alcohol for all individuals.”
 

No smoking guns

Commenting on the guidelines, Steven K. Clinton, MD, PhD, associate director of the Center for Advanced Functional Foods Research and Entrepreneurship at the Ohio State University, Columbus, explained that he didn’t view the change in alcohol as that much of an evolution. “It’s been 8 years since they revised their overall guidelines, and during that time frame, there has been an enormous growth in the evidence that has been used by many organizations,” he said.

Clinton noted that the guidelines are consistent with the whole body of current scientific literature. “It’s very easy to go to the document and look for the ‘smoking gun’ – but the smoking gun is really not one thing,” he said. “It’s a pattern, and what dietitians and nutritionists are telling people is that you need to orchestrate a healthy lifestyle and diet, with a diet that has a foundation of fruits, vegetables, whole grains, and modest intake of refined grains and meat. You are orchestrating an entire pattern to get the maximum benefit.”

Makaroff is an employee of the ACS. Clinton has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

In its updated cancer prevention guidelines, the American Cancer Society now recommends that “it is best not to drink alcohol.”

Previously, ACS suggested that, for those who consume alcoholic beverages, intake should be no more than one drink per day for women or two per day for men. That recommendation is still in place, but is now accompanied by this new, stronger directive.

The revised guidelines also place more emphasis on reducing the consumption of processed and red meat and highly processed foods, and on increasing physical activity.

But importantly, there is also a call for action from public, private, and community organizations to work to together to increase access to affordable, nutritious foods and physical activity.

“Making healthy choices can be challenging for many, and there are strategies included in the guidelines that communities can undertake to help reduce barriers to eating well and physical activity,” said Laura Makaroff, DO, American Cancer Society senior vice president. “Individual choice is an important part of a healthy lifestyle, but having the right policies and environmental factors to break down these barriers is also important, and that is something that clinicians can support.”

The guidelines were published in CA: A Cancer Journal for Clinicians.

The link between cancer and lifestyle factors has long been established, and for the past 4 decades, both government and leading nonprofit health organizations, including the ACS and the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR), have released cancer prevention guidelines and recommendations that focus on managing weight, diet, physical activity, and alcohol consumption.

In 2012, the ACS issued guidelines on diet and physical activity, and their current guideline is largely based on the WCRF/AICR systematic reviews and Continuous Update Project reports, which were last updated in 2018. The ACS guidelines also incorporated systematic reviews conducted by the International Agency on Cancer Research (IARC) and the U.S. Department of Agriculture and the Department of Health and Human Services (USDA/HHS) and other analyses that were published since the WCRF/AICR recommendations were released.
 

Emphasis on three areas

The differences between the old guidelines and the update do not differ dramatically, but Makaroff highlighted a few areas that have increased emphasis.

Time spent being physically active is critical. The recommendation has changed to encourage adults to engage in 150-300 minutes (2.5-5 hours) of moderate-intensity physical activity, or 75-150 minutes (1.25-2.5 hours) of vigorous-intensity physical activity, or an equivalent combination, per week. Achieving or exceeding the upper limit of 300 minutes is optimal.

“That is more than what we have recommended in the past, along with the continued message that children and adolescents engage in at least 1 hour of moderate- or vigorous-intensity activity each day,” she told Medscape Medical News.

The ACS has also increased emphasis on reducing the consumption of processed and red meat. “This is part of a healthy eating pattern and making sure that people are eating food that is high in nutrients that help achieve and maintain a healthy body weight,” said Makaroff.

A healthy diet should include a variety of dark green, red, and orange vegetables; fiber-rich legumes; and fruits with a variety of colors and whole grains, according to the guidelines. Sugar-sweetened beverages, highly processed foods, and refined grain products should be limited or avoided.

The revised dietary recommendations reflect a shift from a “reductionist or nutrient-centric” approach to one that is more “holistic” and that focuses on dietary patterns. In contrast to a focus on individual nutrients and bioactive compounds, the new approach is more consistent with what and how people actually eat, ACS points out.

The third area that Makaroff highlighted is alcohol, where the recommendation is to avoid or limit consumption. “The current update says not to drink alcohol, which is in line with the scientific evidence, but for those people who choose to drink alcohol, to limit it to one drink per day for women and two drinks per day for men.”

Thus, the change here is that the previous guideline only recommended limiting alcohol consumption, while the update suggests that, optimally, it should be avoided completely.

The ACS has also called for community involvement to help implement these goals: “Public, private, and community organizations should work collaboratively at national, state, and local levels to develop, advocate for, and implement policy and environmental changes that increase access to affordable, nutritious foods; provide safe, enjoyable, and accessible opportunities for physical activity; and limit alcohol for all individuals.”
 

No smoking guns

Commenting on the guidelines, Steven K. Clinton, MD, PhD, associate director of the Center for Advanced Functional Foods Research and Entrepreneurship at the Ohio State University, Columbus, explained that he didn’t view the change in alcohol as that much of an evolution. “It’s been 8 years since they revised their overall guidelines, and during that time frame, there has been an enormous growth in the evidence that has been used by many organizations,” he said.

Clinton noted that the guidelines are consistent with the whole body of current scientific literature. “It’s very easy to go to the document and look for the ‘smoking gun’ – but the smoking gun is really not one thing,” he said. “It’s a pattern, and what dietitians and nutritionists are telling people is that you need to orchestrate a healthy lifestyle and diet, with a diet that has a foundation of fruits, vegetables, whole grains, and modest intake of refined grains and meat. You are orchestrating an entire pattern to get the maximum benefit.”

Makaroff is an employee of the ACS. Clinton has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Deciding which cancer patients need immediate treatment and who can safely wait is an uncomfortable assessment for cancer clinicians during the COVID-19 pandemic.

In early April, as the COVID-19 surge was bearing down on New York City, those treatment decisions were “a juggling act every single day,” Jonathan Yang, MD, PhD, a radiation oncologist from New York’s Memorial Sloan Kettering Cancer Center, told Medscape Medical News.

Eventually, a glut of guidelines, recommendations, and expert opinions aimed at helping oncologists emerged. The tools help navigate the complicated risk-benefit analysis of their patient’s risk of infection by SARS-CoV-2 and delaying therapy.

Now, a new tool, which appears to be the first of its kind, quantifies that risk-benefit analysis. But its presence immediately raises the question: can it help?
 

Three-Tier Systems Are Not Very Sophisticated

OncCOVID, a free tool that was launched May 26 by the University of Michigan, allows physicians to individualize risk estimates for delaying treatment of up to 25 early- to late-stage cancers. It includes more than 45 patient characteristics, such as age, location, cancer type, cancer stage, treatment plan, underlying medical conditions, and proposed length of delay in care.

Combining these personal details with data from the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registry and the National Cancer Database, the Michigan app then estimates a patient’s 5- or 10-year survival with immediate vs delayed treatment and weighs that against their risk for COVID-19 using data from the Johns Hopkins Coronavirus Resource Center.

“We thought, isn’t it better to at least provide some evidence-based quantification, rather than a back-of-the-envelope three-tier system that is just sort of ‘made up’?“ explained one of the developers, Daniel Spratt, MD, associate professor of radiation oncology at Michigan Medicine.

Spratt explained that almost every organization, professional society, and government has created something like a three-tier system. Tier 1 represents urgent cases and patients who need immediate treatment. For tier 2, treatment can be delayed weeks or a month, and with tier 3, it can be delayed until the pandemic is over or it’s deemed safe.

“[This system] sounds good at first glance, but in cancer, we’re always talking about personalized medicine, and it’s mind-blowing that these tier systems are only based on urgency and prognosis,” he told Medscape Medical News.

Spratt offered an example. Consider a patient with a very aggressive brain tumor ― that patient is in tier 1 and should undergo treatment immediately. But will the treatment actually help? And how helpful would the procedure be if, say, the patient is 80 years old and, if infected, would have a 30% to 50% chance of dying from the coronavirus?

“If the model says this guy has a 5% harm and this one has 30% harm, you can use that to help prioritize,” summarized Spratt.

The app can generate risk estimates for patients living anywhere in the world and has already been accessed by people from 37 countries. However, Spratt cautions that it is primarily “designed and calibrated for the US.

“The estimates are based on very large US registries, and though it’s probably somewhat similar across much of the world, there’s probably certain cancer types that are more region specific ― especially something like stomach cancer or certain types of head and neck cancer in parts of Asia, for example,” he said.

Although the app’s COVID-19 data are specific to the county level in the United States, elsewhere in the world, it is only country specific.

“We’re using the best data we have for coronavirus, but everyone knows we still have large data gaps,” he acknowledged.
 

How Accurate?

Asked to comment on the app, Richard Bleicher, MD, leader of the Breast Cancer Program at Fox Chase Cancer Center, Philadelphia, praised the effort and the goal but had some concerns.

“Several questions arise, most important of which is, How accurate is this, and how has this been validated, if at all ― especially as it is too soon to see the outcomes of patients affected in this pandemic?” he told Medscape Medical News.

“We are imposing delays on a broad scale because of the coronavirus, and we are getting continuously changing data as we test more patients. But both situations are novel and may not be accurately represented by the data being pulled, because the datasets use patients from a few years ago, and confounders in these datasets may not apply to this situation,” Bleicher continued.

Although acknowledging the “value in delineating the risk of dying from cancer vs the risk of dying from the SARS-CoV-2 pandemic,” Bleicher urged caution in using the tool to make individual patient decisions.

“We need to remember that the best of modeling ... can be wildly inaccurate and needs to be validated using patients having the circumstances in question. ... This won’t be possible until long after the pandemic is completed, and so the model’s accuracy remains unknown.”

That sentiment was echoed by Giampaolo Bianchini, MD, head of the Breast Cancer Group, Department of Medical Oncology, Ospedale San Raffaele, in Milan, Italy.

“Arbitrarily postponing and modifying treatment strategies including surgery, radiation therapy, and medical therapy without properly balancing the risk/benefit ratio may lead to significantly worse cancer-related outcomes, which largely exceed the actual risks for COVID,” he wrote in an email.

“The OncCOVID app is a remarkable attempt to fill the gap between perception and estimation,” he said. The app provides side by side the COVID-19 risk estimation and the consequences of arbitrary deviation from the standard of care, observed Bianchini.

However, he pointed out weaknesses, including the fact that the “data generated in literature are not always of high quality and do not take into consideration relevant characteristics of the disease and treatment benefit. It should for sure be used, but then also interpreted with caution.”

Another Italian group responded more positively.

“In our opinion, it could be a useful tool for clinicians,” wrote colleagues Alessio Cortelinni and Giampiero Porzio, both medical oncologists at San Salvatore Hospital and the University of L’Aquila, in Italy. “This Web app might assist clinicians in balancing the risk/benefit ratio of being treated and/or access to the outpatient cancer center for each kind of patient (both early and advanced stages), in order to make a more tailored counseling,” they wrote in an email. “Importantly, the Web app might help those clinicians who work ‘alone,’ in peripheral centers, without resources, colleagues, and multidisciplinary tumor boards on whom they can rely.”

Bleicher, who was involved in the COVID-19 Breast Cancer Consortium’s recommendations for prioritizing breast cancer treatment, summarized that the app “may end up being close or accurate, but we won’t know except in hindsight.”
 

This article first appeared on Medscape.com.

Deciding which cancer patients need immediate treatment and who can safely wait is an uncomfortable assessment for cancer clinicians during the COVID-19 pandemic.

In early April, as the COVID-19 surge was bearing down on New York City, those treatment decisions were “a juggling act every single day,” Jonathan Yang, MD, PhD, a radiation oncologist from New York’s Memorial Sloan Kettering Cancer Center, told Medscape Medical News.

Eventually, a glut of guidelines, recommendations, and expert opinions aimed at helping oncologists emerged. The tools help navigate the complicated risk-benefit analysis of their patient’s risk of infection by SARS-CoV-2 and delaying therapy.

Now, a new tool, which appears to be the first of its kind, quantifies that risk-benefit analysis. But its presence immediately raises the question: can it help?
 

Three-Tier Systems Are Not Very Sophisticated

OncCOVID, a free tool that was launched May 26 by the University of Michigan, allows physicians to individualize risk estimates for delaying treatment of up to 25 early- to late-stage cancers. It includes more than 45 patient characteristics, such as age, location, cancer type, cancer stage, treatment plan, underlying medical conditions, and proposed length of delay in care.

Combining these personal details with data from the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registry and the National Cancer Database, the Michigan app then estimates a patient’s 5- or 10-year survival with immediate vs delayed treatment and weighs that against their risk for COVID-19 using data from the Johns Hopkins Coronavirus Resource Center.

“We thought, isn’t it better to at least provide some evidence-based quantification, rather than a back-of-the-envelope three-tier system that is just sort of ‘made up’?“ explained one of the developers, Daniel Spratt, MD, associate professor of radiation oncology at Michigan Medicine.

Spratt explained that almost every organization, professional society, and government has created something like a three-tier system. Tier 1 represents urgent cases and patients who need immediate treatment. For tier 2, treatment can be delayed weeks or a month, and with tier 3, it can be delayed until the pandemic is over or it’s deemed safe.

“[This system] sounds good at first glance, but in cancer, we’re always talking about personalized medicine, and it’s mind-blowing that these tier systems are only based on urgency and prognosis,” he told Medscape Medical News.

Spratt offered an example. Consider a patient with a very aggressive brain tumor ― that patient is in tier 1 and should undergo treatment immediately. But will the treatment actually help? And how helpful would the procedure be if, say, the patient is 80 years old and, if infected, would have a 30% to 50% chance of dying from the coronavirus?

“If the model says this guy has a 5% harm and this one has 30% harm, you can use that to help prioritize,” summarized Spratt.

The app can generate risk estimates for patients living anywhere in the world and has already been accessed by people from 37 countries. However, Spratt cautions that it is primarily “designed and calibrated for the US.

“The estimates are based on very large US registries, and though it’s probably somewhat similar across much of the world, there’s probably certain cancer types that are more region specific ― especially something like stomach cancer or certain types of head and neck cancer in parts of Asia, for example,” he said.

Although the app’s COVID-19 data are specific to the county level in the United States, elsewhere in the world, it is only country specific.

“We’re using the best data we have for coronavirus, but everyone knows we still have large data gaps,” he acknowledged.
 

How Accurate?

Asked to comment on the app, Richard Bleicher, MD, leader of the Breast Cancer Program at Fox Chase Cancer Center, Philadelphia, praised the effort and the goal but had some concerns.

“Several questions arise, most important of which is, How accurate is this, and how has this been validated, if at all ― especially as it is too soon to see the outcomes of patients affected in this pandemic?” he told Medscape Medical News.

“We are imposing delays on a broad scale because of the coronavirus, and we are getting continuously changing data as we test more patients. But both situations are novel and may not be accurately represented by the data being pulled, because the datasets use patients from a few years ago, and confounders in these datasets may not apply to this situation,” Bleicher continued.

Although acknowledging the “value in delineating the risk of dying from cancer vs the risk of dying from the SARS-CoV-2 pandemic,” Bleicher urged caution in using the tool to make individual patient decisions.

“We need to remember that the best of modeling ... can be wildly inaccurate and needs to be validated using patients having the circumstances in question. ... This won’t be possible until long after the pandemic is completed, and so the model’s accuracy remains unknown.”

That sentiment was echoed by Giampaolo Bianchini, MD, head of the Breast Cancer Group, Department of Medical Oncology, Ospedale San Raffaele, in Milan, Italy.

“Arbitrarily postponing and modifying treatment strategies including surgery, radiation therapy, and medical therapy without properly balancing the risk/benefit ratio may lead to significantly worse cancer-related outcomes, which largely exceed the actual risks for COVID,” he wrote in an email.

“The OncCOVID app is a remarkable attempt to fill the gap between perception and estimation,” he said. The app provides side by side the COVID-19 risk estimation and the consequences of arbitrary deviation from the standard of care, observed Bianchini.

However, he pointed out weaknesses, including the fact that the “data generated in literature are not always of high quality and do not take into consideration relevant characteristics of the disease and treatment benefit. It should for sure be used, but then also interpreted with caution.”

Another Italian group responded more positively.

“In our opinion, it could be a useful tool for clinicians,” wrote colleagues Alessio Cortelinni and Giampiero Porzio, both medical oncologists at San Salvatore Hospital and the University of L’Aquila, in Italy. “This Web app might assist clinicians in balancing the risk/benefit ratio of being treated and/or access to the outpatient cancer center for each kind of patient (both early and advanced stages), in order to make a more tailored counseling,” they wrote in an email. “Importantly, the Web app might help those clinicians who work ‘alone,’ in peripheral centers, without resources, colleagues, and multidisciplinary tumor boards on whom they can rely.”

Bleicher, who was involved in the COVID-19 Breast Cancer Consortium’s recommendations for prioritizing breast cancer treatment, summarized that the app “may end up being close or accurate, but we won’t know except in hindsight.”
 

This article first appeared on Medscape.com.

Deciding which cancer patients need immediate treatment and who can safely wait is an uncomfortable assessment for cancer clinicians during the COVID-19 pandemic.

In early April, as the COVID-19 surge was bearing down on New York City, those treatment decisions were “a juggling act every single day,” Jonathan Yang, MD, PhD, a radiation oncologist from New York’s Memorial Sloan Kettering Cancer Center, told Medscape Medical News.

Eventually, a glut of guidelines, recommendations, and expert opinions aimed at helping oncologists emerged. The tools help navigate the complicated risk-benefit analysis of their patient’s risk of infection by SARS-CoV-2 and delaying therapy.

Now, a new tool, which appears to be the first of its kind, quantifies that risk-benefit analysis. But its presence immediately raises the question: can it help?
 

Three-Tier Systems Are Not Very Sophisticated

OncCOVID, a free tool that was launched May 26 by the University of Michigan, allows physicians to individualize risk estimates for delaying treatment of up to 25 early- to late-stage cancers. It includes more than 45 patient characteristics, such as age, location, cancer type, cancer stage, treatment plan, underlying medical conditions, and proposed length of delay in care.

Combining these personal details with data from the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) registry and the National Cancer Database, the Michigan app then estimates a patient’s 5- or 10-year survival with immediate vs delayed treatment and weighs that against their risk for COVID-19 using data from the Johns Hopkins Coronavirus Resource Center.

“We thought, isn’t it better to at least provide some evidence-based quantification, rather than a back-of-the-envelope three-tier system that is just sort of ‘made up’?“ explained one of the developers, Daniel Spratt, MD, associate professor of radiation oncology at Michigan Medicine.

Spratt explained that almost every organization, professional society, and government has created something like a three-tier system. Tier 1 represents urgent cases and patients who need immediate treatment. For tier 2, treatment can be delayed weeks or a month, and with tier 3, it can be delayed until the pandemic is over or it’s deemed safe.

“[This system] sounds good at first glance, but in cancer, we’re always talking about personalized medicine, and it’s mind-blowing that these tier systems are only based on urgency and prognosis,” he told Medscape Medical News.

Spratt offered an example. Consider a patient with a very aggressive brain tumor ― that patient is in tier 1 and should undergo treatment immediately. But will the treatment actually help? And how helpful would the procedure be if, say, the patient is 80 years old and, if infected, would have a 30% to 50% chance of dying from the coronavirus?

“If the model says this guy has a 5% harm and this one has 30% harm, you can use that to help prioritize,” summarized Spratt.

The app can generate risk estimates for patients living anywhere in the world and has already been accessed by people from 37 countries. However, Spratt cautions that it is primarily “designed and calibrated for the US.

“The estimates are based on very large US registries, and though it’s probably somewhat similar across much of the world, there’s probably certain cancer types that are more region specific ― especially something like stomach cancer or certain types of head and neck cancer in parts of Asia, for example,” he said.

Although the app’s COVID-19 data are specific to the county level in the United States, elsewhere in the world, it is only country specific.

“We’re using the best data we have for coronavirus, but everyone knows we still have large data gaps,” he acknowledged.
 

How Accurate?

Asked to comment on the app, Richard Bleicher, MD, leader of the Breast Cancer Program at Fox Chase Cancer Center, Philadelphia, praised the effort and the goal but had some concerns.

“Several questions arise, most important of which is, How accurate is this, and how has this been validated, if at all ― especially as it is too soon to see the outcomes of patients affected in this pandemic?” he told Medscape Medical News.

“We are imposing delays on a broad scale because of the coronavirus, and we are getting continuously changing data as we test more patients. But both situations are novel and may not be accurately represented by the data being pulled, because the datasets use patients from a few years ago, and confounders in these datasets may not apply to this situation,” Bleicher continued.

Although acknowledging the “value in delineating the risk of dying from cancer vs the risk of dying from the SARS-CoV-2 pandemic,” Bleicher urged caution in using the tool to make individual patient decisions.

“We need to remember that the best of modeling ... can be wildly inaccurate and needs to be validated using patients having the circumstances in question. ... This won’t be possible until long after the pandemic is completed, and so the model’s accuracy remains unknown.”

That sentiment was echoed by Giampaolo Bianchini, MD, head of the Breast Cancer Group, Department of Medical Oncology, Ospedale San Raffaele, in Milan, Italy.

“Arbitrarily postponing and modifying treatment strategies including surgery, radiation therapy, and medical therapy without properly balancing the risk/benefit ratio may lead to significantly worse cancer-related outcomes, which largely exceed the actual risks for COVID,” he wrote in an email.

“The OncCOVID app is a remarkable attempt to fill the gap between perception and estimation,” he said. The app provides side by side the COVID-19 risk estimation and the consequences of arbitrary deviation from the standard of care, observed Bianchini.

However, he pointed out weaknesses, including the fact that the “data generated in literature are not always of high quality and do not take into consideration relevant characteristics of the disease and treatment benefit. It should for sure be used, but then also interpreted with caution.”

Another Italian group responded more positively.

“In our opinion, it could be a useful tool for clinicians,” wrote colleagues Alessio Cortelinni and Giampiero Porzio, both medical oncologists at San Salvatore Hospital and the University of L’Aquila, in Italy. “This Web app might assist clinicians in balancing the risk/benefit ratio of being treated and/or access to the outpatient cancer center for each kind of patient (both early and advanced stages), in order to make a more tailored counseling,” they wrote in an email. “Importantly, the Web app might help those clinicians who work ‘alone,’ in peripheral centers, without resources, colleagues, and multidisciplinary tumor boards on whom they can rely.”

Bleicher, who was involved in the COVID-19 Breast Cancer Consortium’s recommendations for prioritizing breast cancer treatment, summarized that the app “may end up being close or accurate, but we won’t know except in hindsight.”
 

This article first appeared on Medscape.com.

Adding aggressive local radiotherapy to treatment with tyrosine kinase inhibitor (TKI) significantly improved progression-free and overall survival in patients with previously untreated, EGFR-mutated, oligometastatic non–small cell lung cancer (NSCLC) in a phase 3 trial presented as part of the American Society of Clinical Oncology virtual scientific program.

Sixty-eight patients were randomized at diagnosis to receive a first-generation TKI plus stereotactic body radiation therapy (SBRT) to all disease sites. The other 68 patients were randomized to receive a TKI alone, but 3 patients were lost follow-up and not included in the analysis. The TKIs used were gefitinib, erlotinib, and icotinib.

At baseline, patients had a maximum of two lesions in any one organ and no more than five metastases overall. Patients with brain metastases were excluded.

The median progression-free survival was 20.2 months in the SBRT arm and 12.5 months in the TKI-only arm (hazard ratio, 0.618; P < .001). The median overall survival was 25.5 months and 17.4 months, respectively (HR, 0.682; P < .001).

There were no grade 4/5 adverse events nor any statistically significant between-group differences in grade 3 events.
 

‘Compelling’ data with caveats

The study results suggest that “aggressive local therapy to sites at diagnosis should be explored further in large cohort phase 3 trials as a standard treatment option in this clinical scenario,” said investigator Xiao-shan Wang, MD, PhD, of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital in Chengdu.

“The data are compelling,” Dr. Wang added. “As we attempt to maximize the benefits of EGFR-directed targeted therapies, we are likely going to be moving away from a sequentially administered approach to treatment and considering combinations.”

The new findings, combined with prior phase 2 results, support “incorporation of upfront SBRT with TKI into practice for selected patients with oligometastatic disease, with the open question remaining of how many metastases are too many,” said study discussant Rachel Sanborn, MD, of Providence Cancer Institute Franz Clinic in Portland, Ore.

However, “it’s important to make note of the baseline characteristics of the patients enrolled,” she said.

Twelve percent of patients in the control arm and 4% of those in the SBRT group had EGFR exon 20 insertions. This “imbalance could have negatively impacted the outcomes in the TKI-alone arm,” Dr. Sanborn said.

Also, a higher proportion of patients in the TKI-alone arm received gefitinib, and “there was no information offered on second-line therapies in the study, which might have also affected outcomes,” Dr. Sanborn added.
 

Additional details

The study (NCT02893332) enrolled NSCLC patients with a life expectancy of at least 6 months and an Eastern Cooperative Oncology Group performance status score of 0-2. NSCLC was confirmed by pathology and EGFR mutations by gene sequencing.

The radiation dose was 25-40 Gy in five fractions. Gefitinib was used in 47% of patients in the SBRT arm and 58% of the control group. Erlotinib was used in 44% of the SBRT arm and 35% of controls. Icotinib was used by less than 10% of patients in each group.

Grade 3 skin rash occurred in 50% of patients in the SBRT arm and 62% of those in the TKI-alone arm. Grade 3 pneumonitis occurred in 30% and 15%, respectively. Grade 3 esophagitis occurred in 15% of patients in both arms.

One patient in the TKI arm had severe liver injury. One patient in the SBRT arm fractured a rib, which was considered probably related to the radiation.

Multivariate analysis revealed that, in addition to SBRT, lower baseline performance status score (0 vs. 1-2) and fewer metastases (<2 vs. ≥3) were protective for progression-free survival. Lower performance scores, fewer metastases, lower T stage (T1-2 vs. T3-4), and exon 19 versus exon 20 and 21 mutations were protective for overall survival.

The study arms were well balanced at baseline. The mean patient age was 66.9 years in the SBRT arm and 63.32 years in the TKI-only arm. In both arms, most patients were women (63% and 60%, respectively).

The study was sponsored by Sichuan Provincial People’s Hospital. The investigators and Dr. Sanborn have no relevant disclosures.

aotto@mdedge.com

SOURCE: Wang X et al. ASCO 2020, Abstract 9508.

Adding aggressive local radiotherapy to treatment with tyrosine kinase inhibitor (TKI) significantly improved progression-free and overall survival in patients with previously untreated, EGFR-mutated, oligometastatic non–small cell lung cancer (NSCLC) in a phase 3 trial presented as part of the American Society of Clinical Oncology virtual scientific program.

Sixty-eight patients were randomized at diagnosis to receive a first-generation TKI plus stereotactic body radiation therapy (SBRT) to all disease sites. The other 68 patients were randomized to receive a TKI alone, but 3 patients were lost follow-up and not included in the analysis. The TKIs used were gefitinib, erlotinib, and icotinib.

At baseline, patients had a maximum of two lesions in any one organ and no more than five metastases overall. Patients with brain metastases were excluded.

The median progression-free survival was 20.2 months in the SBRT arm and 12.5 months in the TKI-only arm (hazard ratio, 0.618; P < .001). The median overall survival was 25.5 months and 17.4 months, respectively (HR, 0.682; P < .001).

There were no grade 4/5 adverse events nor any statistically significant between-group differences in grade 3 events.
 

‘Compelling’ data with caveats

The study results suggest that “aggressive local therapy to sites at diagnosis should be explored further in large cohort phase 3 trials as a standard treatment option in this clinical scenario,” said investigator Xiao-shan Wang, MD, PhD, of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital in Chengdu.

“The data are compelling,” Dr. Wang added. “As we attempt to maximize the benefits of EGFR-directed targeted therapies, we are likely going to be moving away from a sequentially administered approach to treatment and considering combinations.”

The new findings, combined with prior phase 2 results, support “incorporation of upfront SBRT with TKI into practice for selected patients with oligometastatic disease, with the open question remaining of how many metastases are too many,” said study discussant Rachel Sanborn, MD, of Providence Cancer Institute Franz Clinic in Portland, Ore.

However, “it’s important to make note of the baseline characteristics of the patients enrolled,” she said.

Twelve percent of patients in the control arm and 4% of those in the SBRT group had EGFR exon 20 insertions. This “imbalance could have negatively impacted the outcomes in the TKI-alone arm,” Dr. Sanborn said.

Also, a higher proportion of patients in the TKI-alone arm received gefitinib, and “there was no information offered on second-line therapies in the study, which might have also affected outcomes,” Dr. Sanborn added.
 

Additional details

The study (NCT02893332) enrolled NSCLC patients with a life expectancy of at least 6 months and an Eastern Cooperative Oncology Group performance status score of 0-2. NSCLC was confirmed by pathology and EGFR mutations by gene sequencing.

The radiation dose was 25-40 Gy in five fractions. Gefitinib was used in 47% of patients in the SBRT arm and 58% of the control group. Erlotinib was used in 44% of the SBRT arm and 35% of controls. Icotinib was used by less than 10% of patients in each group.

Grade 3 skin rash occurred in 50% of patients in the SBRT arm and 62% of those in the TKI-alone arm. Grade 3 pneumonitis occurred in 30% and 15%, respectively. Grade 3 esophagitis occurred in 15% of patients in both arms.

One patient in the TKI arm had severe liver injury. One patient in the SBRT arm fractured a rib, which was considered probably related to the radiation.

Multivariate analysis revealed that, in addition to SBRT, lower baseline performance status score (0 vs. 1-2) and fewer metastases (<2 vs. ≥3) were protective for progression-free survival. Lower performance scores, fewer metastases, lower T stage (T1-2 vs. T3-4), and exon 19 versus exon 20 and 21 mutations were protective for overall survival.

The study arms were well balanced at baseline. The mean patient age was 66.9 years in the SBRT arm and 63.32 years in the TKI-only arm. In both arms, most patients were women (63% and 60%, respectively).

The study was sponsored by Sichuan Provincial People’s Hospital. The investigators and Dr. Sanborn have no relevant disclosures.

aotto@mdedge.com

SOURCE: Wang X et al. ASCO 2020, Abstract 9508.

Adding aggressive local radiotherapy to treatment with tyrosine kinase inhibitor (TKI) significantly improved progression-free and overall survival in patients with previously untreated, EGFR-mutated, oligometastatic non–small cell lung cancer (NSCLC) in a phase 3 trial presented as part of the American Society of Clinical Oncology virtual scientific program.

Sixty-eight patients were randomized at diagnosis to receive a first-generation TKI plus stereotactic body radiation therapy (SBRT) to all disease sites. The other 68 patients were randomized to receive a TKI alone, but 3 patients were lost follow-up and not included in the analysis. The TKIs used were gefitinib, erlotinib, and icotinib.

At baseline, patients had a maximum of two lesions in any one organ and no more than five metastases overall. Patients with brain metastases were excluded.

The median progression-free survival was 20.2 months in the SBRT arm and 12.5 months in the TKI-only arm (hazard ratio, 0.618; P < .001). The median overall survival was 25.5 months and 17.4 months, respectively (HR, 0.682; P < .001).

There were no grade 4/5 adverse events nor any statistically significant between-group differences in grade 3 events.
 

‘Compelling’ data with caveats

The study results suggest that “aggressive local therapy to sites at diagnosis should be explored further in large cohort phase 3 trials as a standard treatment option in this clinical scenario,” said investigator Xiao-shan Wang, MD, PhD, of the University of Electronic Science and Technology of China and Sichuan Provincial People’s Hospital in Chengdu.

“The data are compelling,” Dr. Wang added. “As we attempt to maximize the benefits of EGFR-directed targeted therapies, we are likely going to be moving away from a sequentially administered approach to treatment and considering combinations.”

The new findings, combined with prior phase 2 results, support “incorporation of upfront SBRT with TKI into practice for selected patients with oligometastatic disease, with the open question remaining of how many metastases are too many,” said study discussant Rachel Sanborn, MD, of Providence Cancer Institute Franz Clinic in Portland, Ore.

However, “it’s important to make note of the baseline characteristics of the patients enrolled,” she said.

Twelve percent of patients in the control arm and 4% of those in the SBRT group had EGFR exon 20 insertions. This “imbalance could have negatively impacted the outcomes in the TKI-alone arm,” Dr. Sanborn said.

Also, a higher proportion of patients in the TKI-alone arm received gefitinib, and “there was no information offered on second-line therapies in the study, which might have also affected outcomes,” Dr. Sanborn added.
 

Additional details

The study (NCT02893332) enrolled NSCLC patients with a life expectancy of at least 6 months and an Eastern Cooperative Oncology Group performance status score of 0-2. NSCLC was confirmed by pathology and EGFR mutations by gene sequencing.

The radiation dose was 25-40 Gy in five fractions. Gefitinib was used in 47% of patients in the SBRT arm and 58% of the control group. Erlotinib was used in 44% of the SBRT arm and 35% of controls. Icotinib was used by less than 10% of patients in each group.

Grade 3 skin rash occurred in 50% of patients in the SBRT arm and 62% of those in the TKI-alone arm. Grade 3 pneumonitis occurred in 30% and 15%, respectively. Grade 3 esophagitis occurred in 15% of patients in both arms.

One patient in the TKI arm had severe liver injury. One patient in the SBRT arm fractured a rib, which was considered probably related to the radiation.

Multivariate analysis revealed that, in addition to SBRT, lower baseline performance status score (0 vs. 1-2) and fewer metastases (<2 vs. ≥3) were protective for progression-free survival. Lower performance scores, fewer metastases, lower T stage (T1-2 vs. T3-4), and exon 19 versus exon 20 and 21 mutations were protective for overall survival.

The study arms were well balanced at baseline. The mean patient age was 66.9 years in the SBRT arm and 63.32 years in the TKI-only arm. In both arms, most patients were women (63% and 60%, respectively).

The study was sponsored by Sichuan Provincial People’s Hospital. The investigators and Dr. Sanborn have no relevant disclosures.

aotto@mdedge.com

SOURCE: Wang X et al. ASCO 2020, Abstract 9508.

Lillie Shockney, RN, MAS, a two-time breast cancer survivor and adjunct professor at Johns Hopkins School of Nursing in Baltimore, Maryland, mourns the many losses that her patients with advanced cancer now face in the midst of the COVID-19 pandemic. But in the void of the usual support networks and treatment plans, she sees the resurgence of something that has recently been crowded out: hospice.

The pandemic has forced patients and their physicians to reassess the risk/benefit balance of continuing or embarking on yet another cancer treatment.

“It’s one of the pearls that we will get out of this nightmare,” said Ms. Shockney, who recently retired as administrative director of the cancer survivorship programs at the Sidney Kimmel Comprehensive Cancer Center.

“Physicians have been taught to treat the disease – so as long as there’s a treatment they give another treatment,” she told Medscape Medical News during a Zoom call from her home. “But for some patients with advanced disease, those treatments were making them very sick, so they were trading longevity over quality of life.”

Of course, longevity has never been a guarantee with cancer treatment, and even less so now, with the risk of COVID-19.

“This is going to bring them to some hard discussions,” says Brenda Nevidjon, RN, MSN, chief executive officer at the Oncology Nursing Society.

“We’ve known for a long time that there are patients who are on third- and fourth-round treatment options that have very little evidence of prolonging life or quality of life,” she told Medscape Medical News. “Do we bring these people out of their home to a setting where there could be a fair number of COVID-positive patients? Do we expose them to that?”

Across the world, these dilemmas are pushing cancer specialists to initiate discussions of hospice sooner with patients who have advanced disease, and with more clarity than before.

One of the reasons such conversations have often been avoided is that the concept of hospice is generally misunderstood, said Ms. Shockney.

“Patients think ‘you’re giving up on me, you’ve abandoned me’, but hospice is all about preserving the remainder of their quality of life and letting them have time with family and time to fulfill those elements of experiencing a good and peaceful death,” she said.

Indeed, hospice is “a benefit meant for somebody with at least a 6-month horizon,” agrees Ms. Nevidjon. Yet the average length of hospice in the United States is just 5 days. “It’s at the very, very end, and yet for some of these patients the 6 months they could get in hospice might be a better quality of life than the 4 months on another whole plan of chemotherapy. I can’t imagine that on the backside of this pandemic we will not have learned and we won’t start to change practices around initiating more of these conversations.”
 

Silver lining of this pandemic?

It’s too early into the pandemic to have hard data on whether hospice uptake has increased, but “it’s encouraging to hear that hospice is being discussed and offered sooner as an alternative to that third- or fourth-round chemo,” said Lori Bishop, MHA, RN, vice president of palliative and advanced care at the National Hospice and Palliative Care Organization.

“I agree that improving informed-decision discussions and timely access to hospice is a silver lining of the pandemic,” she told Medscape Medical News.

But she points out that today’s hospice looks quite different than it did before the pandemic, with the immediate and very obvious difference being telehealth, which was not widely utilized previously.

In March, the Centers for Medicare & Medicaid Services expanded telehealth options for hospice providers, something that Ms. Bishop and other hospice providers hope will remain in place after the pandemic passes.

“Telehealth visits are offered to replace some in-home visits both to minimize risk of exposure to COVID-19 and reduce the drain on personal protective equipment,” Bishop explained.

“In-patient hospice programs are also finding unique ways to provide support and connect patients to their loved ones: visitors are allowed but limited to one or two. Music and pet therapy are being provided through the window or virtually and devices such as iPads are being used to help patients connect with loved ones,” she said.

Telehealth links patients out of loneliness, but the one thing it cannot do is provide the comfort of touch – an important part of any hospice program.

“Hand-holding ... I miss that a lot,” says Ms. Shockney, her eyes filling with tears. “When you take somebody’s hand, you don’t even have to speak; that connection, and eye contact, is all you need to help that person emotionally heal.”

This article first appeared on Medscape.com.

Lillie Shockney, RN, MAS, a two-time breast cancer survivor and adjunct professor at Johns Hopkins School of Nursing in Baltimore, Maryland, mourns the many losses that her patients with advanced cancer now face in the midst of the COVID-19 pandemic. But in the void of the usual support networks and treatment plans, she sees the resurgence of something that has recently been crowded out: hospice.

The pandemic has forced patients and their physicians to reassess the risk/benefit balance of continuing or embarking on yet another cancer treatment.

“It’s one of the pearls that we will get out of this nightmare,” said Ms. Shockney, who recently retired as administrative director of the cancer survivorship programs at the Sidney Kimmel Comprehensive Cancer Center.

“Physicians have been taught to treat the disease – so as long as there’s a treatment they give another treatment,” she told Medscape Medical News during a Zoom call from her home. “But for some patients with advanced disease, those treatments were making them very sick, so they were trading longevity over quality of life.”

Of course, longevity has never been a guarantee with cancer treatment, and even less so now, with the risk of COVID-19.

“This is going to bring them to some hard discussions,” says Brenda Nevidjon, RN, MSN, chief executive officer at the Oncology Nursing Society.

“We’ve known for a long time that there are patients who are on third- and fourth-round treatment options that have very little evidence of prolonging life or quality of life,” she told Medscape Medical News. “Do we bring these people out of their home to a setting where there could be a fair number of COVID-positive patients? Do we expose them to that?”

Across the world, these dilemmas are pushing cancer specialists to initiate discussions of hospice sooner with patients who have advanced disease, and with more clarity than before.

One of the reasons such conversations have often been avoided is that the concept of hospice is generally misunderstood, said Ms. Shockney.

“Patients think ‘you’re giving up on me, you’ve abandoned me’, but hospice is all about preserving the remainder of their quality of life and letting them have time with family and time to fulfill those elements of experiencing a good and peaceful death,” she said.

Indeed, hospice is “a benefit meant for somebody with at least a 6-month horizon,” agrees Ms. Nevidjon. Yet the average length of hospice in the United States is just 5 days. “It’s at the very, very end, and yet for some of these patients the 6 months they could get in hospice might be a better quality of life than the 4 months on another whole plan of chemotherapy. I can’t imagine that on the backside of this pandemic we will not have learned and we won’t start to change practices around initiating more of these conversations.”
 

Silver lining of this pandemic?

It’s too early into the pandemic to have hard data on whether hospice uptake has increased, but “it’s encouraging to hear that hospice is being discussed and offered sooner as an alternative to that third- or fourth-round chemo,” said Lori Bishop, MHA, RN, vice president of palliative and advanced care at the National Hospice and Palliative Care Organization.

“I agree that improving informed-decision discussions and timely access to hospice is a silver lining of the pandemic,” she told Medscape Medical News.

But she points out that today’s hospice looks quite different than it did before the pandemic, with the immediate and very obvious difference being telehealth, which was not widely utilized previously.

In March, the Centers for Medicare & Medicaid Services expanded telehealth options for hospice providers, something that Ms. Bishop and other hospice providers hope will remain in place after the pandemic passes.

“Telehealth visits are offered to replace some in-home visits both to minimize risk of exposure to COVID-19 and reduce the drain on personal protective equipment,” Bishop explained.

“In-patient hospice programs are also finding unique ways to provide support and connect patients to their loved ones: visitors are allowed but limited to one or two. Music and pet therapy are being provided through the window or virtually and devices such as iPads are being used to help patients connect with loved ones,” she said.

Telehealth links patients out of loneliness, but the one thing it cannot do is provide the comfort of touch – an important part of any hospice program.

“Hand-holding ... I miss that a lot,” says Ms. Shockney, her eyes filling with tears. “When you take somebody’s hand, you don’t even have to speak; that connection, and eye contact, is all you need to help that person emotionally heal.”

This article first appeared on Medscape.com.

Lillie Shockney, RN, MAS, a two-time breast cancer survivor and adjunct professor at Johns Hopkins School of Nursing in Baltimore, Maryland, mourns the many losses that her patients with advanced cancer now face in the midst of the COVID-19 pandemic. But in the void of the usual support networks and treatment plans, she sees the resurgence of something that has recently been crowded out: hospice.

The pandemic has forced patients and their physicians to reassess the risk/benefit balance of continuing or embarking on yet another cancer treatment.

“It’s one of the pearls that we will get out of this nightmare,” said Ms. Shockney, who recently retired as administrative director of the cancer survivorship programs at the Sidney Kimmel Comprehensive Cancer Center.

“Physicians have been taught to treat the disease – so as long as there’s a treatment they give another treatment,” she told Medscape Medical News during a Zoom call from her home. “But for some patients with advanced disease, those treatments were making them very sick, so they were trading longevity over quality of life.”

Of course, longevity has never been a guarantee with cancer treatment, and even less so now, with the risk of COVID-19.

“This is going to bring them to some hard discussions,” says Brenda Nevidjon, RN, MSN, chief executive officer at the Oncology Nursing Society.

“We’ve known for a long time that there are patients who are on third- and fourth-round treatment options that have very little evidence of prolonging life or quality of life,” she told Medscape Medical News. “Do we bring these people out of their home to a setting where there could be a fair number of COVID-positive patients? Do we expose them to that?”

Across the world, these dilemmas are pushing cancer specialists to initiate discussions of hospice sooner with patients who have advanced disease, and with more clarity than before.

One of the reasons such conversations have often been avoided is that the concept of hospice is generally misunderstood, said Ms. Shockney.

“Patients think ‘you’re giving up on me, you’ve abandoned me’, but hospice is all about preserving the remainder of their quality of life and letting them have time with family and time to fulfill those elements of experiencing a good and peaceful death,” she said.

Indeed, hospice is “a benefit meant for somebody with at least a 6-month horizon,” agrees Ms. Nevidjon. Yet the average length of hospice in the United States is just 5 days. “It’s at the very, very end, and yet for some of these patients the 6 months they could get in hospice might be a better quality of life than the 4 months on another whole plan of chemotherapy. I can’t imagine that on the backside of this pandemic we will not have learned and we won’t start to change practices around initiating more of these conversations.”
 

Silver lining of this pandemic?

It’s too early into the pandemic to have hard data on whether hospice uptake has increased, but “it’s encouraging to hear that hospice is being discussed and offered sooner as an alternative to that third- or fourth-round chemo,” said Lori Bishop, MHA, RN, vice president of palliative and advanced care at the National Hospice and Palliative Care Organization.

“I agree that improving informed-decision discussions and timely access to hospice is a silver lining of the pandemic,” she told Medscape Medical News.

But she points out that today’s hospice looks quite different than it did before the pandemic, with the immediate and very obvious difference being telehealth, which was not widely utilized previously.

In March, the Centers for Medicare & Medicaid Services expanded telehealth options for hospice providers, something that Ms. Bishop and other hospice providers hope will remain in place after the pandemic passes.

“Telehealth visits are offered to replace some in-home visits both to minimize risk of exposure to COVID-19 and reduce the drain on personal protective equipment,” Bishop explained.

“In-patient hospice programs are also finding unique ways to provide support and connect patients to their loved ones: visitors are allowed but limited to one or two. Music and pet therapy are being provided through the window or virtually and devices such as iPads are being used to help patients connect with loved ones,” she said.

Telehealth links patients out of loneliness, but the one thing it cannot do is provide the comfort of touch – an important part of any hospice program.

“Hand-holding ... I miss that a lot,” says Ms. Shockney, her eyes filling with tears. “When you take somebody’s hand, you don’t even have to speak; that connection, and eye contact, is all you need to help that person emotionally heal.”

This article first appeared on Medscape.com.

Adding the immune checkpoint inhibitor pembrolizumab to chemotherapy resulted in a modest improvement in progression-free survival (PFS) but no overall survival (OS) benefit as first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC), results of the KEYNOTE-604 study showed.

Among 453 patients with ES-SCLC randomized to receive pembrolizumab plus etoposide and a platinum agent (EP) or placebo, the median PFS was 4.5 months with pembrolizumab and with 4.3 months with placebo.

This difference, although small, met the prespecified definition for significance, with a hazard ratio favoring pembrolizumab of 0.75 (P = .0023), reported Charles M. Rudin, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

Median OS, the other primary endpoint, was 10.8 months for patients who received pembrolizumab and 9.7 months for those who received placebo. Although this translated to a hazard ratio of 0.80 for pembrolizumab, the P value of .0164 missed the prespecified threshold of .0128 and was therefore not statistically significant.

Dr. Rudin presented these results as part of the American Society of Clinical Oncology virtual scientific program. The study was also published online to coincide with the abstract’s release in the Journal of Clinical Oncology.
 

Beneficial but not practice-changing (yet)

“The addition of pembrolizumab results in durable responses in a subset of patients,” Dr. Rudin said. “I believe additional correlative analyses may help to identify those patients who derive long-term benefit from pembrolizumab.

“The safety profile was manageable with no new or unexpected toxicities. Taken together, these data support the benefit of pembrolizumab in patients with small cell lung cancer and add to the growing body of evidence supporting the value of immune checkpoint inhibitors in a historically difficult-to-treat cancer.”

The results suggest combination pembrolizumab and chemotherapy offers a “viable platform for a novel treatment strategy,” said invited discussant Taofeek K. Owonikoko, MD, PhD, director of thoracic oncology at the Winship Cancer Institute of Emory University in Atlanta.

However, because the trial did not meet the predefined threshold for success, “the immediate impact on practice of this trial is limited at present, and any future impact will have to be supported by regulatory decision,” Dr. Owonikoko said.

“The outcome of this trial also highlights the need for an uncomplicated study design and straightforward analytical plan to ensure accurate results,” he added.
 

Study details

KEYNOTE-604 investigators enrolled 453 patients with ES-SCLC who had no prior systemic therapy, good performance status, and a life expectancy of at least 3 months. Patients were stratified by type of platinum agent (cisplatin vs. carboplatin), Eastern Cooperative Oncology Group performance status 0 or 1, and lactate dehydrogenase levels below or above the upper limit of normal.

Patients were randomized to receive pembrolizumab at 200 mg or normal saline placebo on day 1. Both arms also received etoposide at 100 mg/m² on days 1-3 and investigator’s choice of carboplatin to an area under the curve of 5 on day 1 or cisplatin at 75 mg/m² on day 1 for four cycles every 3 weeks.

The assigned agent (pembrolizumab or placebo) could then be continued as maintenance therapy for up to 31 cycles every 21 days.

Patients with a complete or partial response after cycle 4 could receive up to 25 Gy of prophylactic cranial irradiation delivered over 10 fractions at the investigator’s discretion.
 

Survival and response

As noted, the median PFS was modestly but significantly longer with pembrolizumab plus EP at the second interim analysis, the protocol-specified time for final PFS analysis. The estimated 12-months PFS rates were 13.6% with pembrolizumab plus EP and 3.1% with placebo plus EP.

The final analysis was planned to occur about 31 months after the start of the study or when 284 deaths had occurred, whichever was later. At the final analysis, the median PFS was 4.8 months in the pembrolizumab arm and 4.3 months in the placebo arm. The hazard ratio was 0.73 (95% confidence interval 0.60-0.88).

The 12-month OS rate was 45.1% in the pembrolizumab arm and 39.6% in the placebo arm. Respective 24-month OS rates were 22.5% and 11.2%.

Overall responses rates were 70.6% in the pembrolizumab arm and 61.8% in the placebo arm. There were four and two complete responses per arm, respectively.
 

Safety

Approximately 75% of patients in both arms experienced grade 3 or 4 adverse events.

Fatal adverse events occurred in 6.3% of patients in the pembrolizumab arm and 5.4% in the control arm. The rates of death attributed to study treatment were identical, at 2.7% in each arm.

Events leading to discontinuation occurred in 14.8% of patients who received pembrolizumab and 6.3% of patients who received placebo. Adverse events leading to all treatment discontinuation were similar, at 4% and 3.6%, respectively.

The most common adverse events were hematologic, which are common with EP chemotherapy and did not appear to be exacerbated by the addition of pembrolizumab. Aside from hematologic toxicities, most events were of grade 1 or 2 severity.

Immune-mediated adverse events of any kind occurred in 24.7% of patients in the pembrolizumab arm and 10.3% of those in the placebo arm. Grade 3 or 4 immune-mediated events occurred in 7.2% and 1.3%, respectively.

There were no deaths from immune-mediated reactions in the pembrolizumab arm, but one patient on placebo died from pneumonia.

Merck Sharp & Dohme supported the study. Dr. Rudin disclosed institutional research funding from Merck and a consulting or advisory role for other companies. Dr. Owonikoko disclosed a consulting/advisory role and institutional research funding from Merck and others, and he is a cofounder and stock owner in Cambium Oncology.

SOURCE: Rudin CM et al. ASCO 2020. Abstract 9001.

Adding the immune checkpoint inhibitor pembrolizumab to chemotherapy resulted in a modest improvement in progression-free survival (PFS) but no overall survival (OS) benefit as first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC), results of the KEYNOTE-604 study showed.

Among 453 patients with ES-SCLC randomized to receive pembrolizumab plus etoposide and a platinum agent (EP) or placebo, the median PFS was 4.5 months with pembrolizumab and with 4.3 months with placebo.

This difference, although small, met the prespecified definition for significance, with a hazard ratio favoring pembrolizumab of 0.75 (P = .0023), reported Charles M. Rudin, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

Median OS, the other primary endpoint, was 10.8 months for patients who received pembrolizumab and 9.7 months for those who received placebo. Although this translated to a hazard ratio of 0.80 for pembrolizumab, the P value of .0164 missed the prespecified threshold of .0128 and was therefore not statistically significant.

Dr. Rudin presented these results as part of the American Society of Clinical Oncology virtual scientific program. The study was also published online to coincide with the abstract’s release in the Journal of Clinical Oncology.
 

Beneficial but not practice-changing (yet)

“The addition of pembrolizumab results in durable responses in a subset of patients,” Dr. Rudin said. “I believe additional correlative analyses may help to identify those patients who derive long-term benefit from pembrolizumab.

“The safety profile was manageable with no new or unexpected toxicities. Taken together, these data support the benefit of pembrolizumab in patients with small cell lung cancer and add to the growing body of evidence supporting the value of immune checkpoint inhibitors in a historically difficult-to-treat cancer.”

The results suggest combination pembrolizumab and chemotherapy offers a “viable platform for a novel treatment strategy,” said invited discussant Taofeek K. Owonikoko, MD, PhD, director of thoracic oncology at the Winship Cancer Institute of Emory University in Atlanta.

However, because the trial did not meet the predefined threshold for success, “the immediate impact on practice of this trial is limited at present, and any future impact will have to be supported by regulatory decision,” Dr. Owonikoko said.

“The outcome of this trial also highlights the need for an uncomplicated study design and straightforward analytical plan to ensure accurate results,” he added.
 

Study details

KEYNOTE-604 investigators enrolled 453 patients with ES-SCLC who had no prior systemic therapy, good performance status, and a life expectancy of at least 3 months. Patients were stratified by type of platinum agent (cisplatin vs. carboplatin), Eastern Cooperative Oncology Group performance status 0 or 1, and lactate dehydrogenase levels below or above the upper limit of normal.

Patients were randomized to receive pembrolizumab at 200 mg or normal saline placebo on day 1. Both arms also received etoposide at 100 mg/m² on days 1-3 and investigator’s choice of carboplatin to an area under the curve of 5 on day 1 or cisplatin at 75 mg/m² on day 1 for four cycles every 3 weeks.

The assigned agent (pembrolizumab or placebo) could then be continued as maintenance therapy for up to 31 cycles every 21 days.

Patients with a complete or partial response after cycle 4 could receive up to 25 Gy of prophylactic cranial irradiation delivered over 10 fractions at the investigator’s discretion.
 

Survival and response

As noted, the median PFS was modestly but significantly longer with pembrolizumab plus EP at the second interim analysis, the protocol-specified time for final PFS analysis. The estimated 12-months PFS rates were 13.6% with pembrolizumab plus EP and 3.1% with placebo plus EP.

The final analysis was planned to occur about 31 months after the start of the study or when 284 deaths had occurred, whichever was later. At the final analysis, the median PFS was 4.8 months in the pembrolizumab arm and 4.3 months in the placebo arm. The hazard ratio was 0.73 (95% confidence interval 0.60-0.88).

The 12-month OS rate was 45.1% in the pembrolizumab arm and 39.6% in the placebo arm. Respective 24-month OS rates were 22.5% and 11.2%.

Overall responses rates were 70.6% in the pembrolizumab arm and 61.8% in the placebo arm. There were four and two complete responses per arm, respectively.
 

Safety

Approximately 75% of patients in both arms experienced grade 3 or 4 adverse events.

Fatal adverse events occurred in 6.3% of patients in the pembrolizumab arm and 5.4% in the control arm. The rates of death attributed to study treatment were identical, at 2.7% in each arm.

Events leading to discontinuation occurred in 14.8% of patients who received pembrolizumab and 6.3% of patients who received placebo. Adverse events leading to all treatment discontinuation were similar, at 4% and 3.6%, respectively.

The most common adverse events were hematologic, which are common with EP chemotherapy and did not appear to be exacerbated by the addition of pembrolizumab. Aside from hematologic toxicities, most events were of grade 1 or 2 severity.

Immune-mediated adverse events of any kind occurred in 24.7% of patients in the pembrolizumab arm and 10.3% of those in the placebo arm. Grade 3 or 4 immune-mediated events occurred in 7.2% and 1.3%, respectively.

There were no deaths from immune-mediated reactions in the pembrolizumab arm, but one patient on placebo died from pneumonia.

Merck Sharp & Dohme supported the study. Dr. Rudin disclosed institutional research funding from Merck and a consulting or advisory role for other companies. Dr. Owonikoko disclosed a consulting/advisory role and institutional research funding from Merck and others, and he is a cofounder and stock owner in Cambium Oncology.

SOURCE: Rudin CM et al. ASCO 2020. Abstract 9001.

Adding the immune checkpoint inhibitor pembrolizumab to chemotherapy resulted in a modest improvement in progression-free survival (PFS) but no overall survival (OS) benefit as first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC), results of the KEYNOTE-604 study showed.

Among 453 patients with ES-SCLC randomized to receive pembrolizumab plus etoposide and a platinum agent (EP) or placebo, the median PFS was 4.5 months with pembrolizumab and with 4.3 months with placebo.

This difference, although small, met the prespecified definition for significance, with a hazard ratio favoring pembrolizumab of 0.75 (P = .0023), reported Charles M. Rudin, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York.

Median OS, the other primary endpoint, was 10.8 months for patients who received pembrolizumab and 9.7 months for those who received placebo. Although this translated to a hazard ratio of 0.80 for pembrolizumab, the P value of .0164 missed the prespecified threshold of .0128 and was therefore not statistically significant.

Dr. Rudin presented these results as part of the American Society of Clinical Oncology virtual scientific program. The study was also published online to coincide with the abstract’s release in the Journal of Clinical Oncology.
 

Beneficial but not practice-changing (yet)

“The addition of pembrolizumab results in durable responses in a subset of patients,” Dr. Rudin said. “I believe additional correlative analyses may help to identify those patients who derive long-term benefit from pembrolizumab.

“The safety profile was manageable with no new or unexpected toxicities. Taken together, these data support the benefit of pembrolizumab in patients with small cell lung cancer and add to the growing body of evidence supporting the value of immune checkpoint inhibitors in a historically difficult-to-treat cancer.”

The results suggest combination pembrolizumab and chemotherapy offers a “viable platform for a novel treatment strategy,” said invited discussant Taofeek K. Owonikoko, MD, PhD, director of thoracic oncology at the Winship Cancer Institute of Emory University in Atlanta.

However, because the trial did not meet the predefined threshold for success, “the immediate impact on practice of this trial is limited at present, and any future impact will have to be supported by regulatory decision,” Dr. Owonikoko said.

“The outcome of this trial also highlights the need for an uncomplicated study design and straightforward analytical plan to ensure accurate results,” he added.
 

Study details

KEYNOTE-604 investigators enrolled 453 patients with ES-SCLC who had no prior systemic therapy, good performance status, and a life expectancy of at least 3 months. Patients were stratified by type of platinum agent (cisplatin vs. carboplatin), Eastern Cooperative Oncology Group performance status 0 or 1, and lactate dehydrogenase levels below or above the upper limit of normal.

Patients were randomized to receive pembrolizumab at 200 mg or normal saline placebo on day 1. Both arms also received etoposide at 100 mg/m² on days 1-3 and investigator’s choice of carboplatin to an area under the curve of 5 on day 1 or cisplatin at 75 mg/m² on day 1 for four cycles every 3 weeks.

The assigned agent (pembrolizumab or placebo) could then be continued as maintenance therapy for up to 31 cycles every 21 days.

Patients with a complete or partial response after cycle 4 could receive up to 25 Gy of prophylactic cranial irradiation delivered over 10 fractions at the investigator’s discretion.
 

Survival and response

As noted, the median PFS was modestly but significantly longer with pembrolizumab plus EP at the second interim analysis, the protocol-specified time for final PFS analysis. The estimated 12-months PFS rates were 13.6% with pembrolizumab plus EP and 3.1% with placebo plus EP.

The final analysis was planned to occur about 31 months after the start of the study or when 284 deaths had occurred, whichever was later. At the final analysis, the median PFS was 4.8 months in the pembrolizumab arm and 4.3 months in the placebo arm. The hazard ratio was 0.73 (95% confidence interval 0.60-0.88).

The 12-month OS rate was 45.1% in the pembrolizumab arm and 39.6% in the placebo arm. Respective 24-month OS rates were 22.5% and 11.2%.

Overall responses rates were 70.6% in the pembrolizumab arm and 61.8% in the placebo arm. There were four and two complete responses per arm, respectively.
 

Safety

Approximately 75% of patients in both arms experienced grade 3 or 4 adverse events.

Fatal adverse events occurred in 6.3% of patients in the pembrolizumab arm and 5.4% in the control arm. The rates of death attributed to study treatment were identical, at 2.7% in each arm.

Events leading to discontinuation occurred in 14.8% of patients who received pembrolizumab and 6.3% of patients who received placebo. Adverse events leading to all treatment discontinuation were similar, at 4% and 3.6%, respectively.

The most common adverse events were hematologic, which are common with EP chemotherapy and did not appear to be exacerbated by the addition of pembrolizumab. Aside from hematologic toxicities, most events were of grade 1 or 2 severity.

Immune-mediated adverse events of any kind occurred in 24.7% of patients in the pembrolizumab arm and 10.3% of those in the placebo arm. Grade 3 or 4 immune-mediated events occurred in 7.2% and 1.3%, respectively.

There were no deaths from immune-mediated reactions in the pembrolizumab arm, but one patient on placebo died from pneumonia.

Merck Sharp & Dohme supported the study. Dr. Rudin disclosed institutional research funding from Merck and a consulting or advisory role for other companies. Dr. Owonikoko disclosed a consulting/advisory role and institutional research funding from Merck and others, and he is a cofounder and stock owner in Cambium Oncology.

SOURCE: Rudin CM et al. ASCO 2020. Abstract 9001.

Adding durvalumab to first-line pemetrexed and cisplatin improved survival in patients with unresectable malignant pleural mesothelioma (MPM) in a phase 2 trial, compared with historical controls who received only pemetrexed and cisplatin.

The median overall survival was 20.4 months in patients who received durvalumab plus pemetrexed-cisplatin. This is significantly longer than the median overall survival of 12.1 months (P = .0014) observed with pemetrexed-cisplatin in a prior phase 3 study (J Clin Oncol. 2003 Jul 15;21[14]:2636-44).

The new phase 2 results are “promising,” said lead investigator Patrick Forde, MBBCh, director of the thoracic cancer clinical research program at Johns Hopkins University in Baltimore.

He presented the results as part of the American Society of Clinical Oncology virtual scientific program.

Dr. Forde noted that a phase 3 trial directly comparing pemetrexed-cisplatin plus durvalumab to pemetrexed-cisplatin will begin recruiting this year. The trial is a collaboration between U.S. investigators and Australian researchers who reported their own phase 2 results with durvalumab plus pemetrexed-cisplatin in 2018 (J Thorac Oncol. 2018 Oct;13[10]:S338-339).
 

Study details

Dr. Forde’s phase 2 study enrolled 55 patients with treatment-naive, unresectable MPM. Their median age was 68 years (range, 35-83 years), and 45 (82%) were men. All had an Eastern Cooperative Oncology Group performance status of 0-1.

Epithelioid mesothelioma was the histologic subtype in three-quarters of patients. “It was a fairly typical mesothelioma population,” Dr. Forde said.

The patients received durvalumab at 1,120 mg plus pemetrexed at 500 mg/m² and cisplatin at 75 mg/m² every 3 weeks for up to six cycles. Carboplatin was substituted when cisplatin was contraindicated or patients developed toxicities.

All but one patient had stable or responding disease on radiography and went on to durvalumab maintenance, also given at 1,120 mg every 3 weeks, for up to 1 year from study entry.
 

Results

Dr. Forde said this study had 90% power to detect a 58% improvement in median overall survival, from the 12.1 months seen in historical controls to 19 months, which was the goal of this study.

It was a positive study, he said, as the median overall survival was 20.4 months (P = .0014).

The overall survival rate was 87.2% at 6 months, 70.4% at 12 months, and 44.2% at 24 months. The progression-free survival rate was 69.1% at 6 months, 16.4% at 12 months, and 10.9% at 24 months.

The overall response rate was 56.4%, which comprised 31 partial responses. Forty percent of patients (n = 22) had stable disease. One patient had progressive disease, and one was not evaluable (1.8% each).

To help with future patient selection, the researchers looked for baseline biomarkers that predicted response. Tumor PD-L1 expression, tumor mutation burden, and other potential candidates haven’t worked out so far, but the work continues, Dr. Forde said.

He noted that many of the adverse events in this trial are those typically seen with platinum-based chemotherapy.

Grade 3/4 treatment-emergent adverse events included anemia (n = 14), fatigue (n = 4), decreased appetite (n = 1), and hypomagnesemia (n = 1).

The most common grade 1/2 adverse events of special interest were hypothyroidism (n = 7), rash (n = 5), pruritus (n = 3), AST elevation (n = 3), and hyperthyroidism (n = 3).
 

Putting the results in context

Given the role of inflammation in MPM, durvalumab is among several immunotherapies under investigation for the disease.

A phase 3 French trial showed MPM patients had a median overall survival of 18.8 months with pemetrexed-cisplatin plus bevacizumab versus 16.1 months with pemetrexed-cisplatin only (Lancet. 2016 Apr 2;387[10026]:1405-1414).

The higher overall survival in the French study’s pemetrexed-cisplatin arm, compared with the 2003 trial results, is likely due to the use of modern second-line options, said Marjorie Zauderer, MD, codirector of the mesothelioma program at Memorial Sloan Kettering Cancer Center in New York, who was the discussant for Dr. Forde’s presentation.

“I think the improvement in overall survival presented by Dr. Forde is potentially clinically meaningful,” she said, but it was “well within the 95% confidence interval” of the bevacizumab trial. Even so, “I look forward” to the phase 3 results, she said.

Dr. Zauderer also pointed out an April press release from Bristol Myers Squibb that reported improved survival over pemetrexed-cisplatin with two of the company’s immunotherapies, nivolumab and ipilimumab, not as additions but as replacement first-line therapy. However, the randomized trial data haven’t been released yet. “We are all eager to evaluate this option further,” she said.

AstraZeneca, maker of durvalumab, funded the current study. Dr. Forde is an adviser for the company and reported research funding. Dr. Zauderer reported a relationship with Roche, which markets bevacizumab through its subsidiary, Genentech. She also disclosed research funding from Bristol Myers Squibb.

aotto@mdedge.com

SOURCE: Forde PM et al. ASCO 2020, Abstract 9003.

Adding durvalumab to first-line pemetrexed and cisplatin improved survival in patients with unresectable malignant pleural mesothelioma (MPM) in a phase 2 trial, compared with historical controls who received only pemetrexed and cisplatin.

The median overall survival was 20.4 months in patients who received durvalumab plus pemetrexed-cisplatin. This is significantly longer than the median overall survival of 12.1 months (P = .0014) observed with pemetrexed-cisplatin in a prior phase 3 study (J Clin Oncol. 2003 Jul 15;21[14]:2636-44).

The new phase 2 results are “promising,” said lead investigator Patrick Forde, MBBCh, director of the thoracic cancer clinical research program at Johns Hopkins University in Baltimore.

He presented the results as part of the American Society of Clinical Oncology virtual scientific program.

Dr. Forde noted that a phase 3 trial directly comparing pemetrexed-cisplatin plus durvalumab to pemetrexed-cisplatin will begin recruiting this year. The trial is a collaboration between U.S. investigators and Australian researchers who reported their own phase 2 results with durvalumab plus pemetrexed-cisplatin in 2018 (J Thorac Oncol. 2018 Oct;13[10]:S338-339).
 

Study details

Dr. Forde’s phase 2 study enrolled 55 patients with treatment-naive, unresectable MPM. Their median age was 68 years (range, 35-83 years), and 45 (82%) were men. All had an Eastern Cooperative Oncology Group performance status of 0-1.

Epithelioid mesothelioma was the histologic subtype in three-quarters of patients. “It was a fairly typical mesothelioma population,” Dr. Forde said.

The patients received durvalumab at 1,120 mg plus pemetrexed at 500 mg/m² and cisplatin at 75 mg/m² every 3 weeks for up to six cycles. Carboplatin was substituted when cisplatin was contraindicated or patients developed toxicities.

All but one patient had stable or responding disease on radiography and went on to durvalumab maintenance, also given at 1,120 mg every 3 weeks, for up to 1 year from study entry.
 

Results

Dr. Forde said this study had 90% power to detect a 58% improvement in median overall survival, from the 12.1 months seen in historical controls to 19 months, which was the goal of this study.

It was a positive study, he said, as the median overall survival was 20.4 months (P = .0014).

The overall survival rate was 87.2% at 6 months, 70.4% at 12 months, and 44.2% at 24 months. The progression-free survival rate was 69.1% at 6 months, 16.4% at 12 months, and 10.9% at 24 months.

The overall response rate was 56.4%, which comprised 31 partial responses. Forty percent of patients (n = 22) had stable disease. One patient had progressive disease, and one was not evaluable (1.8% each).

To help with future patient selection, the researchers looked for baseline biomarkers that predicted response. Tumor PD-L1 expression, tumor mutation burden, and other potential candidates haven’t worked out so far, but the work continues, Dr. Forde said.

He noted that many of the adverse events in this trial are those typically seen with platinum-based chemotherapy.

Grade 3/4 treatment-emergent adverse events included anemia (n = 14), fatigue (n = 4), decreased appetite (n = 1), and hypomagnesemia (n = 1).

The most common grade 1/2 adverse events of special interest were hypothyroidism (n = 7), rash (n = 5), pruritus (n = 3), AST elevation (n = 3), and hyperthyroidism (n = 3).
 

Putting the results in context

Given the role of inflammation in MPM, durvalumab is among several immunotherapies under investigation for the disease.

A phase 3 French trial showed MPM patients had a median overall survival of 18.8 months with pemetrexed-cisplatin plus bevacizumab versus 16.1 months with pemetrexed-cisplatin only (Lancet. 2016 Apr 2;387[10026]:1405-1414).

The higher overall survival in the French study’s pemetrexed-cisplatin arm, compared with the 2003 trial results, is likely due to the use of modern second-line options, said Marjorie Zauderer, MD, codirector of the mesothelioma program at Memorial Sloan Kettering Cancer Center in New York, who was the discussant for Dr. Forde’s presentation.

“I think the improvement in overall survival presented by Dr. Forde is potentially clinically meaningful,” she said, but it was “well within the 95% confidence interval” of the bevacizumab trial. Even so, “I look forward” to the phase 3 results, she said.

Dr. Zauderer also pointed out an April press release from Bristol Myers Squibb that reported improved survival over pemetrexed-cisplatin with two of the company’s immunotherapies, nivolumab and ipilimumab, not as additions but as replacement first-line therapy. However, the randomized trial data haven’t been released yet. “We are all eager to evaluate this option further,” she said.

AstraZeneca, maker of durvalumab, funded the current study. Dr. Forde is an adviser for the company and reported research funding. Dr. Zauderer reported a relationship with Roche, which markets bevacizumab through its subsidiary, Genentech. She also disclosed research funding from Bristol Myers Squibb.

aotto@mdedge.com

SOURCE: Forde PM et al. ASCO 2020, Abstract 9003.

Adding durvalumab to first-line pemetrexed and cisplatin improved survival in patients with unresectable malignant pleural mesothelioma (MPM) in a phase 2 trial, compared with historical controls who received only pemetrexed and cisplatin.

The median overall survival was 20.4 months in patients who received durvalumab plus pemetrexed-cisplatin. This is significantly longer than the median overall survival of 12.1 months (P = .0014) observed with pemetrexed-cisplatin in a prior phase 3 study (J Clin Oncol. 2003 Jul 15;21[14]:2636-44).

The new phase 2 results are “promising,” said lead investigator Patrick Forde, MBBCh, director of the thoracic cancer clinical research program at Johns Hopkins University in Baltimore.

He presented the results as part of the American Society of Clinical Oncology virtual scientific program.

Dr. Forde noted that a phase 3 trial directly comparing pemetrexed-cisplatin plus durvalumab to pemetrexed-cisplatin will begin recruiting this year. The trial is a collaboration between U.S. investigators and Australian researchers who reported their own phase 2 results with durvalumab plus pemetrexed-cisplatin in 2018 (J Thorac Oncol. 2018 Oct;13[10]:S338-339).
 

Study details

Dr. Forde’s phase 2 study enrolled 55 patients with treatment-naive, unresectable MPM. Their median age was 68 years (range, 35-83 years), and 45 (82%) were men. All had an Eastern Cooperative Oncology Group performance status of 0-1.

Epithelioid mesothelioma was the histologic subtype in three-quarters of patients. “It was a fairly typical mesothelioma population,” Dr. Forde said.

The patients received durvalumab at 1,120 mg plus pemetrexed at 500 mg/m² and cisplatin at 75 mg/m² every 3 weeks for up to six cycles. Carboplatin was substituted when cisplatin was contraindicated or patients developed toxicities.

All but one patient had stable or responding disease on radiography and went on to durvalumab maintenance, also given at 1,120 mg every 3 weeks, for up to 1 year from study entry.
 

Results

Dr. Forde said this study had 90% power to detect a 58% improvement in median overall survival, from the 12.1 months seen in historical controls to 19 months, which was the goal of this study.

It was a positive study, he said, as the median overall survival was 20.4 months (P = .0014).

The overall survival rate was 87.2% at 6 months, 70.4% at 12 months, and 44.2% at 24 months. The progression-free survival rate was 69.1% at 6 months, 16.4% at 12 months, and 10.9% at 24 months.

The overall response rate was 56.4%, which comprised 31 partial responses. Forty percent of patients (n = 22) had stable disease. One patient had progressive disease, and one was not evaluable (1.8% each).

To help with future patient selection, the researchers looked for baseline biomarkers that predicted response. Tumor PD-L1 expression, tumor mutation burden, and other potential candidates haven’t worked out so far, but the work continues, Dr. Forde said.

He noted that many of the adverse events in this trial are those typically seen with platinum-based chemotherapy.

Grade 3/4 treatment-emergent adverse events included anemia (n = 14), fatigue (n = 4), decreased appetite (n = 1), and hypomagnesemia (n = 1).

The most common grade 1/2 adverse events of special interest were hypothyroidism (n = 7), rash (n = 5), pruritus (n = 3), AST elevation (n = 3), and hyperthyroidism (n = 3).
 

Putting the results in context

Given the role of inflammation in MPM, durvalumab is among several immunotherapies under investigation for the disease.

A phase 3 French trial showed MPM patients had a median overall survival of 18.8 months with pemetrexed-cisplatin plus bevacizumab versus 16.1 months with pemetrexed-cisplatin only (Lancet. 2016 Apr 2;387[10026]:1405-1414).

The higher overall survival in the French study’s pemetrexed-cisplatin arm, compared with the 2003 trial results, is likely due to the use of modern second-line options, said Marjorie Zauderer, MD, codirector of the mesothelioma program at Memorial Sloan Kettering Cancer Center in New York, who was the discussant for Dr. Forde’s presentation.

“I think the improvement in overall survival presented by Dr. Forde is potentially clinically meaningful,” she said, but it was “well within the 95% confidence interval” of the bevacizumab trial. Even so, “I look forward” to the phase 3 results, she said.

Dr. Zauderer also pointed out an April press release from Bristol Myers Squibb that reported improved survival over pemetrexed-cisplatin with two of the company’s immunotherapies, nivolumab and ipilimumab, not as additions but as replacement first-line therapy. However, the randomized trial data haven’t been released yet. “We are all eager to evaluate this option further,” she said.

AstraZeneca, maker of durvalumab, funded the current study. Dr. Forde is an adviser for the company and reported research funding. Dr. Zauderer reported a relationship with Roche, which markets bevacizumab through its subsidiary, Genentech. She also disclosed research funding from Bristol Myers Squibb.

aotto@mdedge.com

SOURCE: Forde PM et al. ASCO 2020, Abstract 9003.

From 7% to nearly 9% of patients with advanced cancer were found to harbor a germline variant with targeted therapeutic actionability in the first study of its kind.

The study involved 11,974 patients with various tumor types. All the patients underwent germline genetic testing from 2015 to 2019 at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, using the next-generation sequencing panel MSK-IMPACT.

This testing showed that 17.1% of patients had variants in cancer predisposition genes, and 7.1%-8.6% had variants that could potentially be targeted.

“Of course, these numbers are not static,” commented lead author Zsofia K. Stadler, MD, a medical oncologist at MSKCC. “And with the emergence of novel targeted treatments with new FDA indications, the therapeutic actionability of germline variants is likely to increase over time.

“Our study demonstrates the first comprehensive assessment of the clinical utility of germline alterations for therapeutic actionability in a population of patients with advanced cancer,” she added.

Dr. Stadler presented the study results during a virtual scientific program of the American Society of Clinical Oncology 2020.

Testing for somatic mutations is evolving as the standard of care in many cancer types, and somatic genomic testing is rapidly becoming an integral part of the regimen for patients with advanced disease. Some studies suggest that 9%-11% of patients harbor actionable genetic alterations, as determined on the basis of tumor profiling.

“The take-home message from this is that now, more than ever before, germline testing is indicated for the selection of cancer treatment,” said Erin Wysong Hofstatter, MD, from Yale University, New Haven, Conn., in a Highlights of the Day session.

An emerging indication for germline testing is the selection of treatment in the advanced setting, she noted. “And it is important to know your test. Remember that tumor sequencing is not a substitute for comprehensive germline testing.”
 

Implications in cancer treatment

For their study, Dr. Stadler and colleagues reviewed the medical records of patients with likely pathogenic/pathogenic germline (LP/P) alterations in genes that had known therapeutic targets so as to identify germline-targeted treatment either in a clinical or research setting.

“Since 2015, patients undergoing MSK-IMPACT may also choose to provide additional consent for secondary germline genetic analysis, wherein up to 88 genes known to be associated with cancer predisposition are analyzed,” she said. “Likely pathogenic and pathogenic germline alterations identified are disclosed to the patient and treating physician via the Clinical Genetic Service.”

A total of 2043 (17.1%) patients who harbored LP/P variants in a cancer predisposition gene were identified. Of these, 11% of patients harbored pathogenic alterations in high or moderate penetrance cancer predisposition genes. When the analysis was limited to genes with targeted therapeutic actionability, or what the authors defined as tier 1 and tier 2 genes, 7.1% of patients (n = 849) harbored a targetable pathogenic germline alteration.

BRCA alterations accounted for half (52%) of the findings, and 20% were associated with Lynch syndrome.

The tier 2 genes, which included PALB2, ATM, RAD51C, and RAD51D, accounted for about a quarter of the findings. Dr. Hofstatter noted that, using strict criteria, 7.1% of patients (n = 849) were found to harbor a pathogenic alteration and a targetable gene. Using less stringent criteria, additional tier 3 genes and additional genes associated with DNA homologous recombination repair brought the number up to 8.6% (n = 1,003).

Therapeutic action

For determining therapeutic actionability, the strict criteria were used; 593 patients (4.95%) with recurrent or metastatic disease were identified. For these patients, consideration of a targeted therapy, either as part of standard care or as part of an investigation or research protocol, was important.

Of this group, 44% received therapy targeting the germline alteration. Regarding specific genes, 50% of BRCA1/2 carriers and 58% of Lynch syndrome patients received targeted treatment. With respect to tier 2 genes, 40% of patients with PALB2, 19% with ATM, and 37% with RAD51C or 51D received a poly (ADP-ribose) polymerase (PARP) inhibitor.

Among patients with a BRCA1/2 mutation who received a PARP inhibitor, 55.1% had breast or ovarian cancer, and 44.8% had other tumor types, including pancreas, prostate, bile duct, gastric cancers. These patients received the drug in a research setting.

For patients with PALB2 alterations who received PARP inhibitors, 53.3% had breast or pancreas cancer, and 46.7% had cancer of the prostate, ovary, or an unknown primary.

Looking ahead

The discussant for the paper, Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, Houston, pointed out that most of the BRCA-positive patients had cancers traditionally associated with the mutation. “There were no patients with PTEN mutations treated, and interestingly, no patients with NF1 were treated,” she said. “But actionability is evolving, as the MEK inhibitor selumitinib was recently approved for NF1.”

Some questions remain unanswered, she noted, such as: “What percentage of patients undergoing tumor-normal testing signed a germline protocol?” and “Does the population introduce a bias – such as younger patients, family history, and so on?”

It is also unknown what percentage of germline alterations were known in comparison with those identified through tumor/normal testing. Also of importance is the fact that in this study, the results of germline testing were delivered in an academic setting, she emphasized. “What if they were delivered elsewhere? What would be the impact of identifying these alterations in an environment with less access to trials?

“But to be fair, it is not easy to seek the germline mutations,” Dr. Meric-Bernstam continued. “These studies were done under institutional review board protocols, and it is important to note that most profiling is done as standard of care without consenting and soliciting patient preference on the return of germline results.”

An infrastructure is needed to return/counsel/offer cascade testing, and “analyses need to be facilitated to ensure that findings can be acted upon in a timely fashion,” she added.

The study was supported by MSKCC internal funding. Dr. Stadler reported relationships (institutional) with Adverum, Alimera Sciences, Allergan, Biomarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Meric-Bernstram reported relationships with numerous pharmaceutical companies.

This article first appeared on Medscape.com.

From 7% to nearly 9% of patients with advanced cancer were found to harbor a germline variant with targeted therapeutic actionability in the first study of its kind.

The study involved 11,974 patients with various tumor types. All the patients underwent germline genetic testing from 2015 to 2019 at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, using the next-generation sequencing panel MSK-IMPACT.

This testing showed that 17.1% of patients had variants in cancer predisposition genes, and 7.1%-8.6% had variants that could potentially be targeted.

“Of course, these numbers are not static,” commented lead author Zsofia K. Stadler, MD, a medical oncologist at MSKCC. “And with the emergence of novel targeted treatments with new FDA indications, the therapeutic actionability of germline variants is likely to increase over time.

“Our study demonstrates the first comprehensive assessment of the clinical utility of germline alterations for therapeutic actionability in a population of patients with advanced cancer,” she added.

Dr. Stadler presented the study results during a virtual scientific program of the American Society of Clinical Oncology 2020.

Testing for somatic mutations is evolving as the standard of care in many cancer types, and somatic genomic testing is rapidly becoming an integral part of the regimen for patients with advanced disease. Some studies suggest that 9%-11% of patients harbor actionable genetic alterations, as determined on the basis of tumor profiling.

“The take-home message from this is that now, more than ever before, germline testing is indicated for the selection of cancer treatment,” said Erin Wysong Hofstatter, MD, from Yale University, New Haven, Conn., in a Highlights of the Day session.

An emerging indication for germline testing is the selection of treatment in the advanced setting, she noted. “And it is important to know your test. Remember that tumor sequencing is not a substitute for comprehensive germline testing.”
 

Implications in cancer treatment

For their study, Dr. Stadler and colleagues reviewed the medical records of patients with likely pathogenic/pathogenic germline (LP/P) alterations in genes that had known therapeutic targets so as to identify germline-targeted treatment either in a clinical or research setting.

“Since 2015, patients undergoing MSK-IMPACT may also choose to provide additional consent for secondary germline genetic analysis, wherein up to 88 genes known to be associated with cancer predisposition are analyzed,” she said. “Likely pathogenic and pathogenic germline alterations identified are disclosed to the patient and treating physician via the Clinical Genetic Service.”

A total of 2043 (17.1%) patients who harbored LP/P variants in a cancer predisposition gene were identified. Of these, 11% of patients harbored pathogenic alterations in high or moderate penetrance cancer predisposition genes. When the analysis was limited to genes with targeted therapeutic actionability, or what the authors defined as tier 1 and tier 2 genes, 7.1% of patients (n = 849) harbored a targetable pathogenic germline alteration.

BRCA alterations accounted for half (52%) of the findings, and 20% were associated with Lynch syndrome.

The tier 2 genes, which included PALB2, ATM, RAD51C, and RAD51D, accounted for about a quarter of the findings. Dr. Hofstatter noted that, using strict criteria, 7.1% of patients (n = 849) were found to harbor a pathogenic alteration and a targetable gene. Using less stringent criteria, additional tier 3 genes and additional genes associated with DNA homologous recombination repair brought the number up to 8.6% (n = 1,003).

Therapeutic action

For determining therapeutic actionability, the strict criteria were used; 593 patients (4.95%) with recurrent or metastatic disease were identified. For these patients, consideration of a targeted therapy, either as part of standard care or as part of an investigation or research protocol, was important.

Of this group, 44% received therapy targeting the germline alteration. Regarding specific genes, 50% of BRCA1/2 carriers and 58% of Lynch syndrome patients received targeted treatment. With respect to tier 2 genes, 40% of patients with PALB2, 19% with ATM, and 37% with RAD51C or 51D received a poly (ADP-ribose) polymerase (PARP) inhibitor.

Among patients with a BRCA1/2 mutation who received a PARP inhibitor, 55.1% had breast or ovarian cancer, and 44.8% had other tumor types, including pancreas, prostate, bile duct, gastric cancers. These patients received the drug in a research setting.

For patients with PALB2 alterations who received PARP inhibitors, 53.3% had breast or pancreas cancer, and 46.7% had cancer of the prostate, ovary, or an unknown primary.

Looking ahead

The discussant for the paper, Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, Houston, pointed out that most of the BRCA-positive patients had cancers traditionally associated with the mutation. “There were no patients with PTEN mutations treated, and interestingly, no patients with NF1 were treated,” she said. “But actionability is evolving, as the MEK inhibitor selumitinib was recently approved for NF1.”

Some questions remain unanswered, she noted, such as: “What percentage of patients undergoing tumor-normal testing signed a germline protocol?” and “Does the population introduce a bias – such as younger patients, family history, and so on?”

It is also unknown what percentage of germline alterations were known in comparison with those identified through tumor/normal testing. Also of importance is the fact that in this study, the results of germline testing were delivered in an academic setting, she emphasized. “What if they were delivered elsewhere? What would be the impact of identifying these alterations in an environment with less access to trials?

“But to be fair, it is not easy to seek the germline mutations,” Dr. Meric-Bernstam continued. “These studies were done under institutional review board protocols, and it is important to note that most profiling is done as standard of care without consenting and soliciting patient preference on the return of germline results.”

An infrastructure is needed to return/counsel/offer cascade testing, and “analyses need to be facilitated to ensure that findings can be acted upon in a timely fashion,” she added.

The study was supported by MSKCC internal funding. Dr. Stadler reported relationships (institutional) with Adverum, Alimera Sciences, Allergan, Biomarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Meric-Bernstram reported relationships with numerous pharmaceutical companies.

This article first appeared on Medscape.com.

From 7% to nearly 9% of patients with advanced cancer were found to harbor a germline variant with targeted therapeutic actionability in the first study of its kind.

The study involved 11,974 patients with various tumor types. All the patients underwent germline genetic testing from 2015 to 2019 at the Memorial Sloan Kettering Cancer Center (MSKCC) in New York, using the next-generation sequencing panel MSK-IMPACT.

This testing showed that 17.1% of patients had variants in cancer predisposition genes, and 7.1%-8.6% had variants that could potentially be targeted.

“Of course, these numbers are not static,” commented lead author Zsofia K. Stadler, MD, a medical oncologist at MSKCC. “And with the emergence of novel targeted treatments with new FDA indications, the therapeutic actionability of germline variants is likely to increase over time.

“Our study demonstrates the first comprehensive assessment of the clinical utility of germline alterations for therapeutic actionability in a population of patients with advanced cancer,” she added.

Dr. Stadler presented the study results during a virtual scientific program of the American Society of Clinical Oncology 2020.

Testing for somatic mutations is evolving as the standard of care in many cancer types, and somatic genomic testing is rapidly becoming an integral part of the regimen for patients with advanced disease. Some studies suggest that 9%-11% of patients harbor actionable genetic alterations, as determined on the basis of tumor profiling.

“The take-home message from this is that now, more than ever before, germline testing is indicated for the selection of cancer treatment,” said Erin Wysong Hofstatter, MD, from Yale University, New Haven, Conn., in a Highlights of the Day session.

An emerging indication for germline testing is the selection of treatment in the advanced setting, she noted. “And it is important to know your test. Remember that tumor sequencing is not a substitute for comprehensive germline testing.”
 

Implications in cancer treatment

For their study, Dr. Stadler and colleagues reviewed the medical records of patients with likely pathogenic/pathogenic germline (LP/P) alterations in genes that had known therapeutic targets so as to identify germline-targeted treatment either in a clinical or research setting.

“Since 2015, patients undergoing MSK-IMPACT may also choose to provide additional consent for secondary germline genetic analysis, wherein up to 88 genes known to be associated with cancer predisposition are analyzed,” she said. “Likely pathogenic and pathogenic germline alterations identified are disclosed to the patient and treating physician via the Clinical Genetic Service.”

A total of 2043 (17.1%) patients who harbored LP/P variants in a cancer predisposition gene were identified. Of these, 11% of patients harbored pathogenic alterations in high or moderate penetrance cancer predisposition genes. When the analysis was limited to genes with targeted therapeutic actionability, or what the authors defined as tier 1 and tier 2 genes, 7.1% of patients (n = 849) harbored a targetable pathogenic germline alteration.

BRCA alterations accounted for half (52%) of the findings, and 20% were associated with Lynch syndrome.

The tier 2 genes, which included PALB2, ATM, RAD51C, and RAD51D, accounted for about a quarter of the findings. Dr. Hofstatter noted that, using strict criteria, 7.1% of patients (n = 849) were found to harbor a pathogenic alteration and a targetable gene. Using less stringent criteria, additional tier 3 genes and additional genes associated with DNA homologous recombination repair brought the number up to 8.6% (n = 1,003).

Therapeutic action

For determining therapeutic actionability, the strict criteria were used; 593 patients (4.95%) with recurrent or metastatic disease were identified. For these patients, consideration of a targeted therapy, either as part of standard care or as part of an investigation or research protocol, was important.

Of this group, 44% received therapy targeting the germline alteration. Regarding specific genes, 50% of BRCA1/2 carriers and 58% of Lynch syndrome patients received targeted treatment. With respect to tier 2 genes, 40% of patients with PALB2, 19% with ATM, and 37% with RAD51C or 51D received a poly (ADP-ribose) polymerase (PARP) inhibitor.

Among patients with a BRCA1/2 mutation who received a PARP inhibitor, 55.1% had breast or ovarian cancer, and 44.8% had other tumor types, including pancreas, prostate, bile duct, gastric cancers. These patients received the drug in a research setting.

For patients with PALB2 alterations who received PARP inhibitors, 53.3% had breast or pancreas cancer, and 46.7% had cancer of the prostate, ovary, or an unknown primary.

Looking ahead

The discussant for the paper, Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at the University of Texas MD Anderson Cancer Center, Houston, pointed out that most of the BRCA-positive patients had cancers traditionally associated with the mutation. “There were no patients with PTEN mutations treated, and interestingly, no patients with NF1 were treated,” she said. “But actionability is evolving, as the MEK inhibitor selumitinib was recently approved for NF1.”

Some questions remain unanswered, she noted, such as: “What percentage of patients undergoing tumor-normal testing signed a germline protocol?” and “Does the population introduce a bias – such as younger patients, family history, and so on?”

It is also unknown what percentage of germline alterations were known in comparison with those identified through tumor/normal testing. Also of importance is the fact that in this study, the results of germline testing were delivered in an academic setting, she emphasized. “What if they were delivered elsewhere? What would be the impact of identifying these alterations in an environment with less access to trials?

“But to be fair, it is not easy to seek the germline mutations,” Dr. Meric-Bernstam continued. “These studies were done under institutional review board protocols, and it is important to note that most profiling is done as standard of care without consenting and soliciting patient preference on the return of germline results.”

An infrastructure is needed to return/counsel/offer cascade testing, and “analyses need to be facilitated to ensure that findings can be acted upon in a timely fashion,” she added.

The study was supported by MSKCC internal funding. Dr. Stadler reported relationships (institutional) with Adverum, Alimera Sciences, Allergan, Biomarin, Fortress Biotech, Genentech/Roche, Novartis, Optos, Regeneron, Regenxbio, and Spark Therapeutics. Dr. Meric-Bernstram reported relationships with numerous pharmaceutical companies.

This article first appeared on Medscape.com.

Poziotinib, a pan-EGFR inhibitor, shrank tumors in a majority of patients with previously treated non–small cell lung cancer and EGFR exon 20 insertion mutations, but most of these patients did not achieve a response in the ongoing phase 2 ZENITH20 study.

The overall response rate (ORR) in the 115 patients was 14.8%, according to Xiuning Le, MD, PhD, of MD Anderson Cancer Center in Houston, who reported these results at the AACR virtual meeting I.

The ORR fell short of the greater than 17% required to meet the primary endpoint, but 65% of patients experienced tumor shrinkage, Dr. Le noted.

Overall, 17 patients had a confirmed partial response, 5 had an unconfirmed partial response, and 62 had stable disease, for a disease control rate of 68.7%.

Responses occurred early and were durable, Dr. Le said. The median duration of response was 7.4 months.

Responses were also consistent across subgroups based on the number of prior lines of therapy and prior EGFR tyrosine kinase inhibitor (TKI) therapy.

The median progression-free survival was 4.2 months.
 

Patients, treatment, and safety

The patients, who were enrolled in the first cohort of the ZENITH20 study, had a median age of 61 years. They had received a median of two prior therapies, with most having received both chemotherapy and immunotherapy.

Poziotinib was given at a once-daily dose of 16 mg for 28-day cycles, with follow-up of 24 months. Dose reductions were allowed for adverse events (AEs).

AEs were on target and consistent with EGFR TKI class effects. The most common AEs were rash, diarrhea, stomatitis, and paronychia.

Grade 3 AEs included rash (28%) and diarrhea (25%). No grade 5 treatment-related AEs occurred.

Dose reductions were common, occurring in 68% of patients. The median relative poziotinib dose intensity was 72%, suggesting that response can be maintained at lower dose levels, Dr. Le said.

Drug interruptions were also common, occurring in 88% of patients. Ten percent of patients discontinued treatment permanently, Dr. Le said, noting that this is consistent with findings in prior large trials of second-generation TKIs.
 

Implications

The results of this study are of note because EGFR is a known driver of NSCLC, Dr. Le said. She explained that, while effective treatments exist for more common EGFR mutations, such as the classic sensitizing exon 21 mutation L858R and exon 19 deletion, no approved targeted therapies are available for the approximately 10% of lung cancer patients whose tumors harbor EGFR exon 20 insertions.

“Those EGFR exon 20 insertions are not sensitive to most of the approved EGFR inhibitors,” Dr. Le said. She noted that, in one study, the median progression-free survival following treatment with an approved agent was 14 months in patients with classical mutations, compared with 2 months in those with exon 20 insertions.

The difference is attributable to molecular structural differences. Exon 20 insertions create a smaller and more shallow EGFR protein interaction surface, Dr. Le explained. “So some of the approved inhibitors don’t fit well into the oncogenic molecule,” she said.

Poziotinib has a small size and shape that can fit into the binding pocket of exon 20, and that, along with its mechanism of action, made it a promising candidate for this population, Dr. Le said. She referenced a study of 44 patients at MD Anderson Cancer Center in which poziotinib produced an ORR of 43%.

In the current study, “[p]oziotinib has further demonstrated clinical activity in previously treated lung cancer patients with EGFR exon 20 insertions ... with a toxicity profile similar to that of other second-generation TKIs,” she said.

The findings underscore the promise of EGFR exon 20 insertions as targets for therapeutic intervention, said invited discussant Taofeek Owonikoko, MD, PhD, of Winship Cancer Institute of Emory University in Atlanta.

“Poziotinib showed modest but meaningful efficacy,” he said. “However, its safety remains a challenge. It is expected that ongoing modifications in the dosing schedule will make it a more tolerable agent.”

“Future studies to systematically explore differential sensitivity of various exon 20 insertion mutations by location will be informative, as will [elucidation of] mechanisms of resistance to prioritize combinatorial strategies to further enhance the efficacy of this drug,” Dr. Owonikoko added.
 

Next steps

Analyses of other cohorts in the ZENITH20 trial will be reported at upcoming conferences as the data mature, Dr. Le noted. Cohorts 2-4 include patients with previously treated HER2 exon 20 insertions and treatment-naive patients with EGFR and HER2 exon 20 insertions, respectively.

Additionally, three new cohorts are being added, including one with patients who have EGFR or HER2 exon 20 insertions, one with EGFR patients who failed prior osimertinib treatment, and one with patients who have atypical EGFR or HER2 mutations.

Rather than the once-daily dosing used in cohorts 1-4, twice-daily dosing will be evaluated in these cohorts, Dr. Le said, explaining that the half-life of poziotinib is about 8 hours.

“Recent pharmacological modeling showed that a [twice-daily] regimen would reduce the maximal serum concentration and increase trough, which could lead to optimized drug coverage,” she said. “This may potentially reduce toxicity and improve patient compliance and efficacy.”

ZENITH20 is sponsored by Spectrum Pharmaceuticals Inc. Dr. Le disclosed relationships with Spectrum as well as Eli Lilly, AstraZeneca, EMD Serono, and Boehringer Ingelheim. Dr. Owonikoko disclosed relationships with many companies, not including Spectrum.

sworcester@mdedge.com

SOURCE: Le X et al. AACR 2020, Abstract CT081.

Poziotinib, a pan-EGFR inhibitor, shrank tumors in a majority of patients with previously treated non–small cell lung cancer and EGFR exon 20 insertion mutations, but most of these patients did not achieve a response in the ongoing phase 2 ZENITH20 study.

The overall response rate (ORR) in the 115 patients was 14.8%, according to Xiuning Le, MD, PhD, of MD Anderson Cancer Center in Houston, who reported these results at the AACR virtual meeting I.

The ORR fell short of the greater than 17% required to meet the primary endpoint, but 65% of patients experienced tumor shrinkage, Dr. Le noted.

Overall, 17 patients had a confirmed partial response, 5 had an unconfirmed partial response, and 62 had stable disease, for a disease control rate of 68.7%.

Responses occurred early and were durable, Dr. Le said. The median duration of response was 7.4 months.

Responses were also consistent across subgroups based on the number of prior lines of therapy and prior EGFR tyrosine kinase inhibitor (TKI) therapy.

The median progression-free survival was 4.2 months.
 

Patients, treatment, and safety

The patients, who were enrolled in the first cohort of the ZENITH20 study, had a median age of 61 years. They had received a median of two prior therapies, with most having received both chemotherapy and immunotherapy.

Poziotinib was given at a once-daily dose of 16 mg for 28-day cycles, with follow-up of 24 months. Dose reductions were allowed for adverse events (AEs).

AEs were on target and consistent with EGFR TKI class effects. The most common AEs were rash, diarrhea, stomatitis, and paronychia.

Grade 3 AEs included rash (28%) and diarrhea (25%). No grade 5 treatment-related AEs occurred.

Dose reductions were common, occurring in 68% of patients. The median relative poziotinib dose intensity was 72%, suggesting that response can be maintained at lower dose levels, Dr. Le said.

Drug interruptions were also common, occurring in 88% of patients. Ten percent of patients discontinued treatment permanently, Dr. Le said, noting that this is consistent with findings in prior large trials of second-generation TKIs.
 

Implications

The results of this study are of note because EGFR is a known driver of NSCLC, Dr. Le said. She explained that, while effective treatments exist for more common EGFR mutations, such as the classic sensitizing exon 21 mutation L858R and exon 19 deletion, no approved targeted therapies are available for the approximately 10% of lung cancer patients whose tumors harbor EGFR exon 20 insertions.

“Those EGFR exon 20 insertions are not sensitive to most of the approved EGFR inhibitors,” Dr. Le said. She noted that, in one study, the median progression-free survival following treatment with an approved agent was 14 months in patients with classical mutations, compared with 2 months in those with exon 20 insertions.

The difference is attributable to molecular structural differences. Exon 20 insertions create a smaller and more shallow EGFR protein interaction surface, Dr. Le explained. “So some of the approved inhibitors don’t fit well into the oncogenic molecule,” she said.

Poziotinib has a small size and shape that can fit into the binding pocket of exon 20, and that, along with its mechanism of action, made it a promising candidate for this population, Dr. Le said. She referenced a study of 44 patients at MD Anderson Cancer Center in which poziotinib produced an ORR of 43%.

In the current study, “[p]oziotinib has further demonstrated clinical activity in previously treated lung cancer patients with EGFR exon 20 insertions ... with a toxicity profile similar to that of other second-generation TKIs,” she said.

The findings underscore the promise of EGFR exon 20 insertions as targets for therapeutic intervention, said invited discussant Taofeek Owonikoko, MD, PhD, of Winship Cancer Institute of Emory University in Atlanta.

“Poziotinib showed modest but meaningful efficacy,” he said. “However, its safety remains a challenge. It is expected that ongoing modifications in the dosing schedule will make it a more tolerable agent.”

“Future studies to systematically explore differential sensitivity of various exon 20 insertion mutations by location will be informative, as will [elucidation of] mechanisms of resistance to prioritize combinatorial strategies to further enhance the efficacy of this drug,” Dr. Owonikoko added.
 

Next steps

Analyses of other cohorts in the ZENITH20 trial will be reported at upcoming conferences as the data mature, Dr. Le noted. Cohorts 2-4 include patients with previously treated HER2 exon 20 insertions and treatment-naive patients with EGFR and HER2 exon 20 insertions, respectively.

Additionally, three new cohorts are being added, including one with patients who have EGFR or HER2 exon 20 insertions, one with EGFR patients who failed prior osimertinib treatment, and one with patients who have atypical EGFR or HER2 mutations.

Rather than the once-daily dosing used in cohorts 1-4, twice-daily dosing will be evaluated in these cohorts, Dr. Le said, explaining that the half-life of poziotinib is about 8 hours.

“Recent pharmacological modeling showed that a [twice-daily] regimen would reduce the maximal serum concentration and increase trough, which could lead to optimized drug coverage,” she said. “This may potentially reduce toxicity and improve patient compliance and efficacy.”

ZENITH20 is sponsored by Spectrum Pharmaceuticals Inc. Dr. Le disclosed relationships with Spectrum as well as Eli Lilly, AstraZeneca, EMD Serono, and Boehringer Ingelheim. Dr. Owonikoko disclosed relationships with many companies, not including Spectrum.

sworcester@mdedge.com

SOURCE: Le X et al. AACR 2020, Abstract CT081.

Poziotinib, a pan-EGFR inhibitor, shrank tumors in a majority of patients with previously treated non–small cell lung cancer and EGFR exon 20 insertion mutations, but most of these patients did not achieve a response in the ongoing phase 2 ZENITH20 study.

The overall response rate (ORR) in the 115 patients was 14.8%, according to Xiuning Le, MD, PhD, of MD Anderson Cancer Center in Houston, who reported these results at the AACR virtual meeting I.

The ORR fell short of the greater than 17% required to meet the primary endpoint, but 65% of patients experienced tumor shrinkage, Dr. Le noted.

Overall, 17 patients had a confirmed partial response, 5 had an unconfirmed partial response, and 62 had stable disease, for a disease control rate of 68.7%.

Responses occurred early and were durable, Dr. Le said. The median duration of response was 7.4 months.

Responses were also consistent across subgroups based on the number of prior lines of therapy and prior EGFR tyrosine kinase inhibitor (TKI) therapy.

The median progression-free survival was 4.2 months.
 

Patients, treatment, and safety

The patients, who were enrolled in the first cohort of the ZENITH20 study, had a median age of 61 years. They had received a median of two prior therapies, with most having received both chemotherapy and immunotherapy.

Poziotinib was given at a once-daily dose of 16 mg for 28-day cycles, with follow-up of 24 months. Dose reductions were allowed for adverse events (AEs).

AEs were on target and consistent with EGFR TKI class effects. The most common AEs were rash, diarrhea, stomatitis, and paronychia.

Grade 3 AEs included rash (28%) and diarrhea (25%). No grade 5 treatment-related AEs occurred.

Dose reductions were common, occurring in 68% of patients. The median relative poziotinib dose intensity was 72%, suggesting that response can be maintained at lower dose levels, Dr. Le said.

Drug interruptions were also common, occurring in 88% of patients. Ten percent of patients discontinued treatment permanently, Dr. Le said, noting that this is consistent with findings in prior large trials of second-generation TKIs.
 

Implications

The results of this study are of note because EGFR is a known driver of NSCLC, Dr. Le said. She explained that, while effective treatments exist for more common EGFR mutations, such as the classic sensitizing exon 21 mutation L858R and exon 19 deletion, no approved targeted therapies are available for the approximately 10% of lung cancer patients whose tumors harbor EGFR exon 20 insertions.

“Those EGFR exon 20 insertions are not sensitive to most of the approved EGFR inhibitors,” Dr. Le said. She noted that, in one study, the median progression-free survival following treatment with an approved agent was 14 months in patients with classical mutations, compared with 2 months in those with exon 20 insertions.

The difference is attributable to molecular structural differences. Exon 20 insertions create a smaller and more shallow EGFR protein interaction surface, Dr. Le explained. “So some of the approved inhibitors don’t fit well into the oncogenic molecule,” she said.

Poziotinib has a small size and shape that can fit into the binding pocket of exon 20, and that, along with its mechanism of action, made it a promising candidate for this population, Dr. Le said. She referenced a study of 44 patients at MD Anderson Cancer Center in which poziotinib produced an ORR of 43%.

In the current study, “[p]oziotinib has further demonstrated clinical activity in previously treated lung cancer patients with EGFR exon 20 insertions ... with a toxicity profile similar to that of other second-generation TKIs,” she said.

The findings underscore the promise of EGFR exon 20 insertions as targets for therapeutic intervention, said invited discussant Taofeek Owonikoko, MD, PhD, of Winship Cancer Institute of Emory University in Atlanta.

“Poziotinib showed modest but meaningful efficacy,” he said. “However, its safety remains a challenge. It is expected that ongoing modifications in the dosing schedule will make it a more tolerable agent.”

“Future studies to systematically explore differential sensitivity of various exon 20 insertion mutations by location will be informative, as will [elucidation of] mechanisms of resistance to prioritize combinatorial strategies to further enhance the efficacy of this drug,” Dr. Owonikoko added.
 

Next steps

Analyses of other cohorts in the ZENITH20 trial will be reported at upcoming conferences as the data mature, Dr. Le noted. Cohorts 2-4 include patients with previously treated HER2 exon 20 insertions and treatment-naive patients with EGFR and HER2 exon 20 insertions, respectively.

Additionally, three new cohorts are being added, including one with patients who have EGFR or HER2 exon 20 insertions, one with EGFR patients who failed prior osimertinib treatment, and one with patients who have atypical EGFR or HER2 mutations.

Rather than the once-daily dosing used in cohorts 1-4, twice-daily dosing will be evaluated in these cohorts, Dr. Le said, explaining that the half-life of poziotinib is about 8 hours.

“Recent pharmacological modeling showed that a [twice-daily] regimen would reduce the maximal serum concentration and increase trough, which could lead to optimized drug coverage,” she said. “This may potentially reduce toxicity and improve patient compliance and efficacy.”

ZENITH20 is sponsored by Spectrum Pharmaceuticals Inc. Dr. Le disclosed relationships with Spectrum as well as Eli Lilly, AstraZeneca, EMD Serono, and Boehringer Ingelheim. Dr. Owonikoko disclosed relationships with many companies, not including Spectrum.

sworcester@mdedge.com

SOURCE: Le X et al. AACR 2020, Abstract CT081.

The Food and Drug Administration has approved ramucirumab (Cyramza) in combination with erlotinib for the first-line treatment of metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 mutations.

The approval was supported by results from the phase 3 RELAY trial (Lancet Oncol. 2019 Dec;20[12]:1655-69). The trial enrolled 449 patients with previously untreated, EGFR-mutated, metastatic NSCLC.



Patients received either ramucirumab at 10 mg/kg or placebo every 2 weeks as an intravenous infusion in combination with erlotinib at 150 mg orally once daily. Patients continued treatment until they progressed or developed unacceptable toxicity. The median progression-free survival was 19.4 months in the ramucirumab-erlotinib arm, compared with 12.4 months in the placebo-erlotinib arm (hazard ratio, 0.59; 95% confidence interval, 0.46-0.76; P < .0001). The overall response rate was 76% in the ramucirumab arm and 75% in the placebo arm. The median duration of response was 18.0 months and 11.1 months, respectively. Overall survival data were not mature at the final analysis.

Adverse events that were more common in the ramucirumab arm were infections, hypertension, stomatitis, proteinuria, alopecia, epistaxis, and peripheral edema. Full prescribing information is available on the FDA website.

lfranki@mdedge.com

The Food and Drug Administration has approved ramucirumab (Cyramza) in combination with erlotinib for the first-line treatment of metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 mutations.

The approval was supported by results from the phase 3 RELAY trial (Lancet Oncol. 2019 Dec;20[12]:1655-69). The trial enrolled 449 patients with previously untreated, EGFR-mutated, metastatic NSCLC.



Patients received either ramucirumab at 10 mg/kg or placebo every 2 weeks as an intravenous infusion in combination with erlotinib at 150 mg orally once daily. Patients continued treatment until they progressed or developed unacceptable toxicity. The median progression-free survival was 19.4 months in the ramucirumab-erlotinib arm, compared with 12.4 months in the placebo-erlotinib arm (hazard ratio, 0.59; 95% confidence interval, 0.46-0.76; P < .0001). The overall response rate was 76% in the ramucirumab arm and 75% in the placebo arm. The median duration of response was 18.0 months and 11.1 months, respectively. Overall survival data were not mature at the final analysis.

Adverse events that were more common in the ramucirumab arm were infections, hypertension, stomatitis, proteinuria, alopecia, epistaxis, and peripheral edema. Full prescribing information is available on the FDA website.

lfranki@mdedge.com

The Food and Drug Administration has approved ramucirumab (Cyramza) in combination with erlotinib for the first-line treatment of metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 mutations.

The approval was supported by results from the phase 3 RELAY trial (Lancet Oncol. 2019 Dec;20[12]:1655-69). The trial enrolled 449 patients with previously untreated, EGFR-mutated, metastatic NSCLC.



Patients received either ramucirumab at 10 mg/kg or placebo every 2 weeks as an intravenous infusion in combination with erlotinib at 150 mg orally once daily. Patients continued treatment until they progressed or developed unacceptable toxicity. The median progression-free survival was 19.4 months in the ramucirumab-erlotinib arm, compared with 12.4 months in the placebo-erlotinib arm (hazard ratio, 0.59; 95% confidence interval, 0.46-0.76; P < .0001). The overall response rate was 76% in the ramucirumab arm and 75% in the placebo arm. The median duration of response was 18.0 months and 11.1 months, respectively. Overall survival data were not mature at the final analysis.

Adverse events that were more common in the ramucirumab arm were infections, hypertension, stomatitis, proteinuria, alopecia, epistaxis, and peripheral edema. Full prescribing information is available on the FDA website.

lfranki@mdedge.com

Among patients with HER2-mutated non–small cell lung cancer (NSCLC) in an ongoing phase 2 trial, treatment with trastuzumab deruxtecan (T-DXd) has yielded a high response rate, and the median duration of response has not yet been reached, an investigator reported.

The overall response rate (ORR) exceeded 60% among these heavily pretreated patients, with an estimated median progression-free survival (PFS) of 14 months, according to Egbert F. Smit, MD, PhD, of the Netherlands Cancer Institute.

Interstitial lung disease is an identified risk associated with T-DXd treatment, though the events in the DESTINY-Lung01 trial have been low-grade and have not resulted in any deaths, Dr. Smit said when presenting results from the trial as part of the American Society of Clinical Oncology virtual scientific program.

“These data demonstrate the potential of T-DXd as a new treatment option for patients with HER2-mutated non–small-cell lung cancer,” Dr. Smit said.
 

‘A good targeted therapy’

The findings are a “nice early confirmation” of the initial results seen with T-DXd in an earlier, smaller, phase 1 population, said invited discussant Grace K. Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

“Trastuzumab-DXd showed clinical outcomes that meet the standards of what we expect a good targeted therapy should have in terms of overall response rate and progression free survival,” Dr. Dy said.

She noted that the ORR in DESTINY-Lung01 exceeds a 23% ORR seen among NSCLC patients treated with dual HER2-targeted therapy – trastuzumab plus pertuzumab – in a basket trial (J Clin Oncol. 2018 Feb 20;36[6]:536-42). Moreover, the response and PFS data “far surpass” results seen to date with oral tyrosine kinase inhibitors, including pyrotinib, poziotinib, neratinib, and afatinib.

The T-DXd results also look favorable in comparison to another antibody-drug conjugate, ado trastuzumab emtansine, Dr. Dy added, referencing another basket trial in which investigators reported an ORR of 44% and a median PFS of 5 months among 18 patients with advanced HER2-mutant lung adenocarcinomas (J Clin Oncol. 2018 Aug 20;36[24]:2532-7).

“Although T-DM1 [ado trastuzumab emtansine] demonstrated some degree of activity, its lower dosing, which was limited by the payload, lower drug-antibody ratio, and shorter half-life likely explain why results were better with T-DXd,” Dr. Dy said.

T-DXd was, in fact, designed to deliver an optimal antitumor effect, according to Dr. Smit.

The treatment incorporates a humanized anti-HER2 IgG1 monoclonal antibody that has the same amino acid sequence as trastuzumab. The antibody is attached via a cleavable, tumor-selective linker to a payload of deruxtecan, a topoisomerase I inhibitor.

The resulting antibody-drug conjugate has a high drug-to-antibody ratio, with 8 DXd molecules per monoclonal antibody, according to Dr. Smit.

Study details

The DESTINY-Lung01 trial included 42 patients with HER2-mutated NSCLC who received T-DXd at a dose of 6.4 mg/kg every 3 weeks. The patients’ median age was 63 years, and about 64% were female. Eastern Cooperative Oncology Group performance status was 0 in about one-quarter of the patients, and 1 in the remainder.

Patients had received up to six prior lines of treatment, including platinum-based chemotherapy in about 91%, a PD-1 or PD-L1 inhibitor in 55%, and docetaxel in 19%.

The confirmed ORR by independent central review was 61.9% (26/42). That included a single complete response (2.4%) and 25 partial responses (59.5%).

The duration of response was not reached (95% CI, 5.3 months to not estimable), and the median PFS was 14.0 months (95% CI, 6.4-14.0 months).

All patients experienced a treatment-related adverse event. Treatment-related events of grade 3 or greater were seen in 22 patients (52%). These mainly included decreased neutrophil count, anemia, nausea, vomiting, and fatigue.

There were five cases of interstitial lung disease, all of which were grade 2. In four cases, T-DXd was withdrawn. In one case, the drug was interrupted. All patients were treated with steroids.

“Two [patients] recovered, one recovered with sequelae, one was recovering, and one had not recovered by data cutoff,” Dr. Smit said.

DESTINY-Lung01 also includes a cohort of patients with HER2-expressing NSCLC not reported at the meeting. Enrollment in the HER2-mutated cohort that was reported has been expanded with another 50 patients to “better characterize the risk-benefit ratio,” Dr. Smit said.

The DESTINY-Lung01 study is sponsored by Daiichi Sankyo Inc. Dr. Smit reported relationships with Daiichi Sankyo and many other companies. Dr. Dy reported disclosures related to Amgen, AstraZeneca/Medimmune, GlaxoSmithKline, Takeda, and Tesaro.

SOURCE: Smit EF et al. ASCO 2020, Abstract 9504.

Among patients with HER2-mutated non–small cell lung cancer (NSCLC) in an ongoing phase 2 trial, treatment with trastuzumab deruxtecan (T-DXd) has yielded a high response rate, and the median duration of response has not yet been reached, an investigator reported.

The overall response rate (ORR) exceeded 60% among these heavily pretreated patients, with an estimated median progression-free survival (PFS) of 14 months, according to Egbert F. Smit, MD, PhD, of the Netherlands Cancer Institute.

Interstitial lung disease is an identified risk associated with T-DXd treatment, though the events in the DESTINY-Lung01 trial have been low-grade and have not resulted in any deaths, Dr. Smit said when presenting results from the trial as part of the American Society of Clinical Oncology virtual scientific program.

“These data demonstrate the potential of T-DXd as a new treatment option for patients with HER2-mutated non–small-cell lung cancer,” Dr. Smit said.
 

‘A good targeted therapy’

The findings are a “nice early confirmation” of the initial results seen with T-DXd in an earlier, smaller, phase 1 population, said invited discussant Grace K. Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

“Trastuzumab-DXd showed clinical outcomes that meet the standards of what we expect a good targeted therapy should have in terms of overall response rate and progression free survival,” Dr. Dy said.

She noted that the ORR in DESTINY-Lung01 exceeds a 23% ORR seen among NSCLC patients treated with dual HER2-targeted therapy – trastuzumab plus pertuzumab – in a basket trial (J Clin Oncol. 2018 Feb 20;36[6]:536-42). Moreover, the response and PFS data “far surpass” results seen to date with oral tyrosine kinase inhibitors, including pyrotinib, poziotinib, neratinib, and afatinib.

The T-DXd results also look favorable in comparison to another antibody-drug conjugate, ado trastuzumab emtansine, Dr. Dy added, referencing another basket trial in which investigators reported an ORR of 44% and a median PFS of 5 months among 18 patients with advanced HER2-mutant lung adenocarcinomas (J Clin Oncol. 2018 Aug 20;36[24]:2532-7).

“Although T-DM1 [ado trastuzumab emtansine] demonstrated some degree of activity, its lower dosing, which was limited by the payload, lower drug-antibody ratio, and shorter half-life likely explain why results were better with T-DXd,” Dr. Dy said.

T-DXd was, in fact, designed to deliver an optimal antitumor effect, according to Dr. Smit.

The treatment incorporates a humanized anti-HER2 IgG1 monoclonal antibody that has the same amino acid sequence as trastuzumab. The antibody is attached via a cleavable, tumor-selective linker to a payload of deruxtecan, a topoisomerase I inhibitor.

The resulting antibody-drug conjugate has a high drug-to-antibody ratio, with 8 DXd molecules per monoclonal antibody, according to Dr. Smit.

Study details

The DESTINY-Lung01 trial included 42 patients with HER2-mutated NSCLC who received T-DXd at a dose of 6.4 mg/kg every 3 weeks. The patients’ median age was 63 years, and about 64% were female. Eastern Cooperative Oncology Group performance status was 0 in about one-quarter of the patients, and 1 in the remainder.

Patients had received up to six prior lines of treatment, including platinum-based chemotherapy in about 91%, a PD-1 or PD-L1 inhibitor in 55%, and docetaxel in 19%.

The confirmed ORR by independent central review was 61.9% (26/42). That included a single complete response (2.4%) and 25 partial responses (59.5%).

The duration of response was not reached (95% CI, 5.3 months to not estimable), and the median PFS was 14.0 months (95% CI, 6.4-14.0 months).

All patients experienced a treatment-related adverse event. Treatment-related events of grade 3 or greater were seen in 22 patients (52%). These mainly included decreased neutrophil count, anemia, nausea, vomiting, and fatigue.

There were five cases of interstitial lung disease, all of which were grade 2. In four cases, T-DXd was withdrawn. In one case, the drug was interrupted. All patients were treated with steroids.

“Two [patients] recovered, one recovered with sequelae, one was recovering, and one had not recovered by data cutoff,” Dr. Smit said.

DESTINY-Lung01 also includes a cohort of patients with HER2-expressing NSCLC not reported at the meeting. Enrollment in the HER2-mutated cohort that was reported has been expanded with another 50 patients to “better characterize the risk-benefit ratio,” Dr. Smit said.

The DESTINY-Lung01 study is sponsored by Daiichi Sankyo Inc. Dr. Smit reported relationships with Daiichi Sankyo and many other companies. Dr. Dy reported disclosures related to Amgen, AstraZeneca/Medimmune, GlaxoSmithKline, Takeda, and Tesaro.

SOURCE: Smit EF et al. ASCO 2020, Abstract 9504.

Among patients with HER2-mutated non–small cell lung cancer (NSCLC) in an ongoing phase 2 trial, treatment with trastuzumab deruxtecan (T-DXd) has yielded a high response rate, and the median duration of response has not yet been reached, an investigator reported.

The overall response rate (ORR) exceeded 60% among these heavily pretreated patients, with an estimated median progression-free survival (PFS) of 14 months, according to Egbert F. Smit, MD, PhD, of the Netherlands Cancer Institute.

Interstitial lung disease is an identified risk associated with T-DXd treatment, though the events in the DESTINY-Lung01 trial have been low-grade and have not resulted in any deaths, Dr. Smit said when presenting results from the trial as part of the American Society of Clinical Oncology virtual scientific program.

“These data demonstrate the potential of T-DXd as a new treatment option for patients with HER2-mutated non–small-cell lung cancer,” Dr. Smit said.
 

‘A good targeted therapy’

The findings are a “nice early confirmation” of the initial results seen with T-DXd in an earlier, smaller, phase 1 population, said invited discussant Grace K. Dy, MD, of Roswell Park Comprehensive Cancer Center in Buffalo, N.Y.

“Trastuzumab-DXd showed clinical outcomes that meet the standards of what we expect a good targeted therapy should have in terms of overall response rate and progression free survival,” Dr. Dy said.

She noted that the ORR in DESTINY-Lung01 exceeds a 23% ORR seen among NSCLC patients treated with dual HER2-targeted therapy – trastuzumab plus pertuzumab – in a basket trial (J Clin Oncol. 2018 Feb 20;36[6]:536-42). Moreover, the response and PFS data “far surpass” results seen to date with oral tyrosine kinase inhibitors, including pyrotinib, poziotinib, neratinib, and afatinib.

The T-DXd results also look favorable in comparison to another antibody-drug conjugate, ado trastuzumab emtansine, Dr. Dy added, referencing another basket trial in which investigators reported an ORR of 44% and a median PFS of 5 months among 18 patients with advanced HER2-mutant lung adenocarcinomas (J Clin Oncol. 2018 Aug 20;36[24]:2532-7).

“Although T-DM1 [ado trastuzumab emtansine] demonstrated some degree of activity, its lower dosing, which was limited by the payload, lower drug-antibody ratio, and shorter half-life likely explain why results were better with T-DXd,” Dr. Dy said.

T-DXd was, in fact, designed to deliver an optimal antitumor effect, according to Dr. Smit.

The treatment incorporates a humanized anti-HER2 IgG1 monoclonal antibody that has the same amino acid sequence as trastuzumab. The antibody is attached via a cleavable, tumor-selective linker to a payload of deruxtecan, a topoisomerase I inhibitor.

The resulting antibody-drug conjugate has a high drug-to-antibody ratio, with 8 DXd molecules per monoclonal antibody, according to Dr. Smit.

Study details

The DESTINY-Lung01 trial included 42 patients with HER2-mutated NSCLC who received T-DXd at a dose of 6.4 mg/kg every 3 weeks. The patients’ median age was 63 years, and about 64% were female. Eastern Cooperative Oncology Group performance status was 0 in about one-quarter of the patients, and 1 in the remainder.

Patients had received up to six prior lines of treatment, including platinum-based chemotherapy in about 91%, a PD-1 or PD-L1 inhibitor in 55%, and docetaxel in 19%.

The confirmed ORR by independent central review was 61.9% (26/42). That included a single complete response (2.4%) and 25 partial responses (59.5%).

The duration of response was not reached (95% CI, 5.3 months to not estimable), and the median PFS was 14.0 months (95% CI, 6.4-14.0 months).

All patients experienced a treatment-related adverse event. Treatment-related events of grade 3 or greater were seen in 22 patients (52%). These mainly included decreased neutrophil count, anemia, nausea, vomiting, and fatigue.

There were five cases of interstitial lung disease, all of which were grade 2. In four cases, T-DXd was withdrawn. In one case, the drug was interrupted. All patients were treated with steroids.

“Two [patients] recovered, one recovered with sequelae, one was recovering, and one had not recovered by data cutoff,” Dr. Smit said.

DESTINY-Lung01 also includes a cohort of patients with HER2-expressing NSCLC not reported at the meeting. Enrollment in the HER2-mutated cohort that was reported has been expanded with another 50 patients to “better characterize the risk-benefit ratio,” Dr. Smit said.

The DESTINY-Lung01 study is sponsored by Daiichi Sankyo Inc. Dr. Smit reported relationships with Daiichi Sankyo and many other companies. Dr. Dy reported disclosures related to Amgen, AstraZeneca/Medimmune, GlaxoSmithKline, Takeda, and Tesaro.

SOURCE: Smit EF et al. ASCO 2020, Abstract 9504.