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Virtual Reality Brings Relief to Hospitalized Patients With Cancer
suggests a new randomized controlled trial.
While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.
“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”
To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
Study Methods and Results
Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.
“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”
The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.
“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.
Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.
“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
Downsides to Using VR
Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.
Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
Future VR Research
“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”
This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.
suggests a new randomized controlled trial.
While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.
“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”
To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
Study Methods and Results
Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.
“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”
The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.
“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.
Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.
“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
Downsides to Using VR
Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.
Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
Future VR Research
“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”
This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.
suggests a new randomized controlled trial.
While both interventions brought some pain relief, VR therapy yielded greater, longer-lasting comfort, reported lead author Hunter Groninger, MD, of MedStar Health Research Institute, Hyattsville, Maryland, and colleagues.
“Investigators have explored immersive VR interventions in cancer populations for a variety of indications including anxiety, depression, fatigue, and procedure‐associated pain, particularly among patients with pediatric cancer and adult breast cancer,” the investigators wrote in Cancer. “Nevertheless, despite growing evidence supporting the efficacy of VR‐delivered interventions for analgesia, few data address its role to mitigate cancer‐related pain specifically.”
To address this knowledge gap, Dr. Groninger and colleagues enrolled 128 adult hospitalized patients with cancer of any kind, all of whom had moderate to severe pain (self-reported score at least 4 out of 10) within the past 24 hours.
Study Methods and Results
Patients were randomized to receive either 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy.
“[The VR therapy] provides noncompetitive experiences in which the user can move around and explore natural environments (e.g., beachscape, forest) from standing, seated, or fixed positions, including within a hospital bed or chair,” the investigators wrote. “We provided over‐the‐ear headphones to assure high sound quality for the experience in the virtual natural environment.”
The two-dimensional intervention, delivered via electronic tablet, featured a meditation with images of natural landscapes and instrumental background music.
“We chose this active control because it is readily available and reflects content similar to relaxation‐focused television channels that are increasingly common in hospital settings,” the investigators noted.
Compared with this more common approach, patients who received VR therapy had significantly greater immediate reduction in pain (mean change in pain score, –1.4 vs –0.7; P = .03). Twenty-four hours later, improvements in the VR group generally persisted, while pain level in the two-dimensional group returned almost to baseline (P = .004). In addition, patients in the VR group reported significantly greater improvements in general distress and pain bothersomeness.
“VR therapies may modulate the pain experience by reducing the level of attention paid to noxious stimuli, thereby suppressing transmission of painful sensations via pain processing pathways to the cerebral cortex, particularly with more active VR experiences compared to passive experiences,” the investigators wrote.
Downsides to Using VR
Although VR brought more benefit, participants in the VR group more often reported difficulty using the intervention compared with those who interacted with an electronic tablet.
Plus, one VR user described mild dizziness that resolved with pharmacologic intervention. Still, approximately 9 out of 10 participants in each group reported willingness to try the intervention again.
Future VR Research
“Virtual reality is a rapidly evolving technology with a wealth of potential patient‐facing applications,” the investigators wrote. “Future studies should explore repeated use, optimal dosing, and impact on VR therapy on opioid analgesic requirements as well as usability testing, VR content preferences and facilitators of analgesia, and barriers and facilitators to use in acute care settings.”
This study was supported by the American Cancer Society. The investigators disclosed no conflicts of interest.
FROM CANCER
Should Opioids Be Used for Chronic Cancer Pain?
from legal concerns to threats of violence, say the authors of new research.
These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.
“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
Who Should Manage Chronic Cancer Pain?
Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.
“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?
To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.
These interviews yielded three themes.
First, no “medical home” exists for chronic pain management in cancer survivors.
“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.
Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.
“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”
The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.
“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”
Meanwhile, a palliative care provider described legal pressure from the opposite direction:
“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”
Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?
After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.
They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.
Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.
This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.
from legal concerns to threats of violence, say the authors of new research.
These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.
“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
Who Should Manage Chronic Cancer Pain?
Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.
“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?
To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.
These interviews yielded three themes.
First, no “medical home” exists for chronic pain management in cancer survivors.
“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.
Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.
“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”
The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.
“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”
Meanwhile, a palliative care provider described legal pressure from the opposite direction:
“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”
Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?
After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.
They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.
Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.
This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.
from legal concerns to threats of violence, say the authors of new research.
These findings suggest that evidence-based, systematic guidance is needed to steer opioid usage in cancer survivorship, wrote lead author Hailey W. Bulls, PhD, of the University of Pittsburgh, and colleagues.
“Prescription opioids are considered the standard of care to treat moderate to severe cancer pain during active treatment, yet guidance in the posttreatment survivorship phase is much less clear,” the investigators wrote. “Existing clinical resources recognize that opioid prescribing in survivorship is complex and nuanced and that the relative benefits and risks in this population are not fully understood.”
Who Should Manage Chronic Cancer Pain?
Despite the knowledge gap, survivors are typically excluded from long-term opioid use studies, leaving providers in a largely data-free zone. Simultaneously, patients who had been receiving focused care during their cancer treatment find themselves with an ill-defined health care team.
“Without a clear transition of care, survivors may seek pain management services from a variety of specialties, including oncologists, palliative care clinicians, primary care clinicians, and pain management specialists,” the investigators wrote. “However, many clinicians may view pain management to be outside of their skill set and may not be well equipped to handle opioid continuation or deprescribing [or] to manage the potential consequences of long‐term opioid use like side effects, misuse, and/or opioid use disorder.”
What Factors Guide Opioid Prescribing Practices for Chronic Cancer Pain?
To learn more about prescribing practices in this setting, Dr. Bulls and colleagues conducted qualitative interviews with 20 providers representing four specialties: oncology (n = 5), palliative care (n = 8), primary care (n = 5), and pain management (n = 2). Eighteen of these participants were physicians and two were advanced practice providers. Average time in clinical practice was about 16 years.
These interviews yielded three themes.
First, no “medical home” exists for chronic pain management in cancer survivors.
“Although clinicians generally agreed that minimizing the role of opioids in chronic pain management in cancer survivors was desirable, they described a lack of common treatment protocols to guide pain management in survivorship,” the investigators wrote.
Second, the interviews revealed that prescribing strategies are partly driven by peer pressure, sometimes leading to tension between providers and feelings of self-doubt.
“I feel like there’s been this weird judgment thing that’s happened [to] the prescribers,” one primary care provider said during the interview. “Because, when I trained … pain was a vital sign, and we were supposed to treat pain, and now I feel like we’re all being judged for that.”
The third theme revolved around fear of consequences resulting from prescribing practices, including fears of violent repercussions.
“You may not know, but pain specialists have been shot in this country for [refusing to prescribe opioids],” one pain management specialist said during the interview. “There’s been a number of shootings of pain specialists who would not prescribe opioids. So, I mean, there’s real issues of violence.”
Meanwhile, a palliative care provider described legal pressure from the opposite direction:
“I think there’s a lot of fear of litigiousness … and loss of licenses. That sort of makes them pressure us into not prescribing opioids or sticking with a certain number per day that might not be therapeutic for a patient.”
Reflecting on these themes, the investigators identified “a fundamental uncertainty in survivorship pain management.”
What Strategies Might Improve Opioid Prescribing Practices for Chronic Cancer Pain?
After sharing their attitudes about prescribing opioids for chronic cancer pain, the clinicians were asked for suggestions to improve the situation.
They offered four main suggestions: create relevant guidelines, increase education and access to pain management options for clinicians, increase interdisciplinary communication across medical subspecialties, and promote multidisciplinary care in the survivorship setting.
Dr. Bulls and colleagues supported these strategies in their concluding remarks and called for more research.
This study was supported by the National Institute of Drug Abuse, the National Institutes of Health, the National Center for Advancing Translational Sciences, and the National Cancer Institute. The investigators disclosed relationships with Arcadia Health Solutions and Biomotivate.
FROM CANCER
CHEST grant recipient studying increase in lung cancer diagnoses among Chinese American women
In his prior research, Chien-Ching Li, PhD, MPH, focused on promoting lung cancer screening in Chinese American men, a population that frequently smokes heavily. But last year, he applied for a CHEST grant that’s shifting his focus to another demographic: Chinese American women who do not smoke, especially those with limited English proficiency.
“They are developing lung cancer, and we don’t know why,” said Dr. Li, an associate professor of Health Systems Management at Rush University.
In fact, 57% of Asian American women diagnosed with lung cancer never smoked cigarettes.
What’s behind this rise in lung cancer in women who have never smoked compared with men, and particularly in Asian American women? One possibility: While Chinese American women may never smoke themselves, they frequently live with partners or family members who do. (About 28% of Chinese American men smoke heavily, Dr. Li said.)
“We think secondhand smoke might be one of the key risk factors, because they’re living with people who smoke,” Dr. Li said. His prior research shows that the majority of Chinese American men in greater Chicagoland—89%—are married, and many of them smoke or have a history of smoking.
With the CHEST grant Dr. Li received in October 2023, he’s working to increase awareness among Chinese American women about the risks of secondhand smoke and “reduce the health disparity in lung cancer among women,” Dr. Li said.
Developing culturally sensitive materials for a high-risk group
While many lung cancer reduction efforts focus on people who smoke, there are plenty of pamphlets designed to inform about the risks incurred when breathing in secondhand smoke.
These handouts, however, aren’t always available in languages spoken by Chinese Americans. Nor is it as simple as hiring a translator; doing so may make the pamphlets readable to the women, but it won’t necessarily make the text culturally appropriate.
This is what Dr. Li—along with his coinvestigators, Alicia Matthews, PhD, a professor of clinical psychology at Columbia University, and Hong Liu, PhD, of the Midwest Asian Health Association—seeks to change, with funding from the CHEST grant. Their goal is four-pronged:
1. Discovery: Dr. Li and his team are currently surveying Chinese American women who have never smoked but who live with people who smoke in greater Chicagoland. These surveys will help them learn more about what (if anything) this group knows about the health risks associated with secondhand smoke and other types of environmental smoke.
2. Identify: These surveys, along with focus group interviews with select participants, will help reveal barriers standing in the way of reducing the women’s exposure to secondhand smoke—as well as ways to encourage habits to reduce risk.
3. Develop: All the information gained through surveys and conversations will then be analyzed and used to craft targeted, translated, and culturally appropriate materials on secondhand smoke, conveying communication strategies the women can use to persuade their partners to quit smoking and ways to build a smoke-free household.
4. Evaluate: The effectiveness of the new materials will be tested to assess the change in the women’s knowledge, as well as any uptick in taking steps to reduce exposure or sign up for screening.
Using the CHEST grant as a building block to more grants—and more information
Dr. Li and his collaborators are still in the early stages of using the CHEST grant: gathering up participants and surveying them.
But there’s much ahead. With the CHEST grant in hand, Dr. Li plans to apply for grants from the National Institutes of Health (NIH): first, an NIH Exploratory/Developmental Research Grant Award (R21) to help achieve that fourth aim of evaluating how the intervention works. And next, they’ll apply for an NIH Research Project Grant Program (R01), which will fund an even larger trial.
“Not many studies focus on identifying the risk factors with lung cancer associated with Chinese American [women who have never smoked],” Dr. Li said. “This is why we want to focus on this area to provide more knowledge and make more contributions to research.”
Projects like this are made possible by generous contributions from CHEST donors. Support the future of chest medicine by visiting https://chestnet.org/donate.
In his prior research, Chien-Ching Li, PhD, MPH, focused on promoting lung cancer screening in Chinese American men, a population that frequently smokes heavily. But last year, he applied for a CHEST grant that’s shifting his focus to another demographic: Chinese American women who do not smoke, especially those with limited English proficiency.
“They are developing lung cancer, and we don’t know why,” said Dr. Li, an associate professor of Health Systems Management at Rush University.
In fact, 57% of Asian American women diagnosed with lung cancer never smoked cigarettes.
What’s behind this rise in lung cancer in women who have never smoked compared with men, and particularly in Asian American women? One possibility: While Chinese American women may never smoke themselves, they frequently live with partners or family members who do. (About 28% of Chinese American men smoke heavily, Dr. Li said.)
“We think secondhand smoke might be one of the key risk factors, because they’re living with people who smoke,” Dr. Li said. His prior research shows that the majority of Chinese American men in greater Chicagoland—89%—are married, and many of them smoke or have a history of smoking.
With the CHEST grant Dr. Li received in October 2023, he’s working to increase awareness among Chinese American women about the risks of secondhand smoke and “reduce the health disparity in lung cancer among women,” Dr. Li said.
Developing culturally sensitive materials for a high-risk group
While many lung cancer reduction efforts focus on people who smoke, there are plenty of pamphlets designed to inform about the risks incurred when breathing in secondhand smoke.
These handouts, however, aren’t always available in languages spoken by Chinese Americans. Nor is it as simple as hiring a translator; doing so may make the pamphlets readable to the women, but it won’t necessarily make the text culturally appropriate.
This is what Dr. Li—along with his coinvestigators, Alicia Matthews, PhD, a professor of clinical psychology at Columbia University, and Hong Liu, PhD, of the Midwest Asian Health Association—seeks to change, with funding from the CHEST grant. Their goal is four-pronged:
1. Discovery: Dr. Li and his team are currently surveying Chinese American women who have never smoked but who live with people who smoke in greater Chicagoland. These surveys will help them learn more about what (if anything) this group knows about the health risks associated with secondhand smoke and other types of environmental smoke.
2. Identify: These surveys, along with focus group interviews with select participants, will help reveal barriers standing in the way of reducing the women’s exposure to secondhand smoke—as well as ways to encourage habits to reduce risk.
3. Develop: All the information gained through surveys and conversations will then be analyzed and used to craft targeted, translated, and culturally appropriate materials on secondhand smoke, conveying communication strategies the women can use to persuade their partners to quit smoking and ways to build a smoke-free household.
4. Evaluate: The effectiveness of the new materials will be tested to assess the change in the women’s knowledge, as well as any uptick in taking steps to reduce exposure or sign up for screening.
Using the CHEST grant as a building block to more grants—and more information
Dr. Li and his collaborators are still in the early stages of using the CHEST grant: gathering up participants and surveying them.
But there’s much ahead. With the CHEST grant in hand, Dr. Li plans to apply for grants from the National Institutes of Health (NIH): first, an NIH Exploratory/Developmental Research Grant Award (R21) to help achieve that fourth aim of evaluating how the intervention works. And next, they’ll apply for an NIH Research Project Grant Program (R01), which will fund an even larger trial.
“Not many studies focus on identifying the risk factors with lung cancer associated with Chinese American [women who have never smoked],” Dr. Li said. “This is why we want to focus on this area to provide more knowledge and make more contributions to research.”
Projects like this are made possible by generous contributions from CHEST donors. Support the future of chest medicine by visiting https://chestnet.org/donate.
In his prior research, Chien-Ching Li, PhD, MPH, focused on promoting lung cancer screening in Chinese American men, a population that frequently smokes heavily. But last year, he applied for a CHEST grant that’s shifting his focus to another demographic: Chinese American women who do not smoke, especially those with limited English proficiency.
“They are developing lung cancer, and we don’t know why,” said Dr. Li, an associate professor of Health Systems Management at Rush University.
In fact, 57% of Asian American women diagnosed with lung cancer never smoked cigarettes.
What’s behind this rise in lung cancer in women who have never smoked compared with men, and particularly in Asian American women? One possibility: While Chinese American women may never smoke themselves, they frequently live with partners or family members who do. (About 28% of Chinese American men smoke heavily, Dr. Li said.)
“We think secondhand smoke might be one of the key risk factors, because they’re living with people who smoke,” Dr. Li said. His prior research shows that the majority of Chinese American men in greater Chicagoland—89%—are married, and many of them smoke or have a history of smoking.
With the CHEST grant Dr. Li received in October 2023, he’s working to increase awareness among Chinese American women about the risks of secondhand smoke and “reduce the health disparity in lung cancer among women,” Dr. Li said.
Developing culturally sensitive materials for a high-risk group
While many lung cancer reduction efforts focus on people who smoke, there are plenty of pamphlets designed to inform about the risks incurred when breathing in secondhand smoke.
These handouts, however, aren’t always available in languages spoken by Chinese Americans. Nor is it as simple as hiring a translator; doing so may make the pamphlets readable to the women, but it won’t necessarily make the text culturally appropriate.
This is what Dr. Li—along with his coinvestigators, Alicia Matthews, PhD, a professor of clinical psychology at Columbia University, and Hong Liu, PhD, of the Midwest Asian Health Association—seeks to change, with funding from the CHEST grant. Their goal is four-pronged:
1. Discovery: Dr. Li and his team are currently surveying Chinese American women who have never smoked but who live with people who smoke in greater Chicagoland. These surveys will help them learn more about what (if anything) this group knows about the health risks associated with secondhand smoke and other types of environmental smoke.
2. Identify: These surveys, along with focus group interviews with select participants, will help reveal barriers standing in the way of reducing the women’s exposure to secondhand smoke—as well as ways to encourage habits to reduce risk.
3. Develop: All the information gained through surveys and conversations will then be analyzed and used to craft targeted, translated, and culturally appropriate materials on secondhand smoke, conveying communication strategies the women can use to persuade their partners to quit smoking and ways to build a smoke-free household.
4. Evaluate: The effectiveness of the new materials will be tested to assess the change in the women’s knowledge, as well as any uptick in taking steps to reduce exposure or sign up for screening.
Using the CHEST grant as a building block to more grants—and more information
Dr. Li and his collaborators are still in the early stages of using the CHEST grant: gathering up participants and surveying them.
But there’s much ahead. With the CHEST grant in hand, Dr. Li plans to apply for grants from the National Institutes of Health (NIH): first, an NIH Exploratory/Developmental Research Grant Award (R21) to help achieve that fourth aim of evaluating how the intervention works. And next, they’ll apply for an NIH Research Project Grant Program (R01), which will fund an even larger trial.
“Not many studies focus on identifying the risk factors with lung cancer associated with Chinese American [women who have never smoked],” Dr. Li said. “This is why we want to focus on this area to provide more knowledge and make more contributions to research.”
Projects like this are made possible by generous contributions from CHEST donors. Support the future of chest medicine by visiting https://chestnet.org/donate.
A Banned Chemical That Is Still Causing Cancer
This transcript has been edited for clarity.
These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.
So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.
PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.
But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.
PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.
This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.
What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.
In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.
In other words, we can’t prove they’re cancerous — but come on, they probably are.
Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).
Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.
The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.
Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.
This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.
This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.
After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.
But the key finding is deaths due to cancer. After adjustment, cancer deaths occurred four times as frequently among those in the high PBDE group, and that is a statistically significant difference.
To be fair, cancer deaths were rare in this cohort. The vast majority of people did not die of anything during the follow-up period regardless of PBDE level. But the data are strongly suggestive of the carcinogenicity of these chemicals.
I should also point out that the researchers are linking the PBDE level at a single time point to all these future events. If PBDE levels remain relatively stable within an individual over time, that’s fine, but if they tend to vary with intake of different foods for example, this would not be captured and would actually lead to an underestimation of the cancer risk.
The researchers also didn’t have granular enough data to determine the type of cancer, but they do show that rates are similar between men and women, which might point away from the more sex-specific cancer etiologies. Clearly, some more work is needed.
Of course, I started this piece by telling you that these chemicals are already pretty much banned in the United States. What are we supposed to do about these findings? Studies have examined the primary ongoing sources of PBDE in our environment and it seems like most of our exposure will be coming from the food we eat due to that biomagnification thing: high-fat fish, meat and dairy products, and fish oil supplements. It may be worth some investigation into the relative adulteration of these products with this new old carcinogen.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.
So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.
PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.
But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.
PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.
This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.
What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.
In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.
In other words, we can’t prove they’re cancerous — but come on, they probably are.
Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).
Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.
The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.
Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.
This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.
This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.
After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.
But the key finding is deaths due to cancer. After adjustment, cancer deaths occurred four times as frequently among those in the high PBDE group, and that is a statistically significant difference.
To be fair, cancer deaths were rare in this cohort. The vast majority of people did not die of anything during the follow-up period regardless of PBDE level. But the data are strongly suggestive of the carcinogenicity of these chemicals.
I should also point out that the researchers are linking the PBDE level at a single time point to all these future events. If PBDE levels remain relatively stable within an individual over time, that’s fine, but if they tend to vary with intake of different foods for example, this would not be captured and would actually lead to an underestimation of the cancer risk.
The researchers also didn’t have granular enough data to determine the type of cancer, but they do show that rates are similar between men and women, which might point away from the more sex-specific cancer etiologies. Clearly, some more work is needed.
Of course, I started this piece by telling you that these chemicals are already pretty much banned in the United States. What are we supposed to do about these findings? Studies have examined the primary ongoing sources of PBDE in our environment and it seems like most of our exposure will be coming from the food we eat due to that biomagnification thing: high-fat fish, meat and dairy products, and fish oil supplements. It may be worth some investigation into the relative adulteration of these products with this new old carcinogen.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
These types of stories usually end with a call for regulation — to ban said chemical or substance, or to regulate it — but in this case, that has already happened. This new carcinogen I’m telling you about is actually an old chemical. And it has not been manufactured or legally imported in the US since 2013.
So, why bother? Because in this case, the chemical — or, really, a group of chemicals called polybrominated diphenyl ethers (PBDEs) — are still around: in our soil, in our food, and in our blood.
PBDEs are a group of compounds that confer flame-retardant properties to plastics, and they were used extensively in the latter part of the 20th century in electronic enclosures, business equipment, and foam cushioning in upholstery.
But there was a problem. They don’t chemically bond to plastics; they are just sort of mixed in, which means they can leach out. They are hydrophobic, meaning they don’t get washed out of soil, and, when ingested or inhaled by humans, they dissolve in our fat stores, making it difficult for our normal excretory systems to excrete them.
PBDEs biomagnify. Small animals can take them up from contaminated soil or water, and those animals are eaten by larger animals, which accumulate higher concentrations of the chemicals. This bioaccumulation increases as you move up the food web until you get to an apex predator — like you and me.
This is true of lots of chemicals, of course. The concern arises when these chemicals are toxic. To date, the toxicity data for PBDEs were pretty limited. There were some animal studies where rats were exposed to extremely high doses and they developed liver lesions — but I am always very wary of extrapolating high-dose rat toxicity studies to humans. There was also some suggestion that the chemicals could be endocrine disruptors, affecting breast and thyroid tissue.
What about cancer? In 2016, the International Agency for Research on Cancer concluded there was “inadequate evidence in humans for the carcinogencity of” PBDEs.
In the same report, though, they suggested PBDEs are “probably carcinogenic to humans” based on mechanistic studies.
In other words, we can’t prove they’re cancerous — but come on, they probably are.
Finally, we have some evidence that really pushes us toward the carcinogenic conclusion, in the form of this study, appearing in JAMA Network Open. It’s a nice bit of epidemiology leveraging the population-based National Health and Nutrition Examination Survey (NHANES).
Researchers measured PBDE levels in blood samples from 1100 people enrolled in NHANES in 2003 and 2004 and linked them to death records collected over the next 20 years or so.
The first thing to note is that the researchers were able to measure PBDEs in the blood samples. They were in there. They were detectable. And they were variable. Dividing the 1100 participants into low, medium, and high PBDE tertiles, you can see a nearly 10-fold difference across the population.
Importantly, not many baseline variables correlated with PBDE levels. People in the highest group were a bit younger but had a fairly similar sex distribution, race, ethnicity, education, income, physical activity, smoking status, and body mass index.
This is not a randomized trial, of course — but at least based on these data, exposure levels do seem fairly random, which is what you would expect from an environmental toxin that percolates up through the food chain. They are often somewhat indiscriminate.
This similarity in baseline characteristics between people with low or high blood levels of PBDE also allows us to make some stronger inferences about the observed outcomes. Let’s take a look at them.
After adjustment for baseline factors, individuals in the highest PBDE group had a 43% higher rate of death from any cause over the follow-up period. This was not enough to achieve statistical significance, but it was close.
But the key finding is deaths due to cancer. After adjustment, cancer deaths occurred four times as frequently among those in the high PBDE group, and that is a statistically significant difference.
To be fair, cancer deaths were rare in this cohort. The vast majority of people did not die of anything during the follow-up period regardless of PBDE level. But the data are strongly suggestive of the carcinogenicity of these chemicals.
I should also point out that the researchers are linking the PBDE level at a single time point to all these future events. If PBDE levels remain relatively stable within an individual over time, that’s fine, but if they tend to vary with intake of different foods for example, this would not be captured and would actually lead to an underestimation of the cancer risk.
The researchers also didn’t have granular enough data to determine the type of cancer, but they do show that rates are similar between men and women, which might point away from the more sex-specific cancer etiologies. Clearly, some more work is needed.
Of course, I started this piece by telling you that these chemicals are already pretty much banned in the United States. What are we supposed to do about these findings? Studies have examined the primary ongoing sources of PBDE in our environment and it seems like most of our exposure will be coming from the food we eat due to that biomagnification thing: high-fat fish, meat and dairy products, and fish oil supplements. It may be worth some investigation into the relative adulteration of these products with this new old carcinogen.
Dr. F. Perry Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Lung Cancer Vaccine Gets Injection of Funding for Research and Development
Development of a , according to a press release from the University of Oxford, England.
A team of scientists from the University of Oxford, the Francis Crick Institute, and University College London (UCL) will receive funding from the Cancer Research UK and the CRIS Cancer Foundation.
The LungVax vaccine is based on technology similar to that used in the creation of the successful Oxford/AstraZeneca COVID-19 vaccine and will carry a DNA strand that trains the immune system to recognize the neoantigens that indicate abnormal lung cancer cells and then activate the immune system to kill these cells and stop the cancer, according to the statement.
Initially, scientists are working to develop a vaccine that triggers an immune response in the lab setting. If successful, the vaccine will move directly into a clinical trial. “If the subsequent early trial delivers promising results, the vaccine could then be scaled up to bigger trials for people at high risk of lung cancer,” according to the release.
Help for High-Risk Patients
Lung cancer is diagnosed in approximately 48,000 individuals in the United Kingdom each year, and the average 10-year survival is only 10%, Tim Elliott, MD, professor of immuno-oncology at the University of Oxford and lead researcher on the LungVax project, said in an interview. Nearly three-quarters of the 35,000 annual deaths are preventable by quitting smoking, which remains the best risk reduction strategy to date, he said. However, “an intervention such as a vaccine, given when people are healthy and are more likely to have a strong immune system, could benefit many thousands per year in the UK and 1.8 million patients worldwide,” he said.
Preliminary Trial Plans
The initial trial of the vaccine is a collaboration between Oxford University, UCL, and the Francis Crick Institute, Dr. Elliott said. The trial is a culmination of research into the biology and genetics of lung cancer at UCL and vaccine design research at the University of Oxford.
“We are at a very early stage of the program, which will develop over the next 6 years if all goes to plan,” said Dr. Elliott. The vaccine is designed on the basis of shared lung cancer antigens and packaged into the ChAdOx delivery system that proved successful as the Oxford-AstraZeneca COVID-19 vaccine, he said.
“We intend to vaccinate individuals who have had curative surgery for their lung cancer after being diagnosed with a very early stage of the disease,” Dr. Elliott said.
Challenges to vaccine development include knowing whether there is a clinical benefit, Dr. Elliott noted. “Our clinical trial is calculated to show up to 15% reduction in risk over 3-5 years, but only long-term follow-up will really tell us whether the immune responses we see to the vaccine within the first few weeks will have a long-term effect,” he emphasized.
In clinical practice, “these people are cancer-free and healthy after surgery,” said Dr. Elliott. However, “they are at a high risk of recurrence; 30%-70% of ex-patients will develop new cancer in their lifetime and in the majority of cases that will happen within 2 years after surgery,” he said. “We think that vaccinating them against common lung cancer antigens could reduce this risk significantly and remove some of the uncertainty that they live with after their operation.”
Vaccine Has Potential for Immense Impact
Lung cancer remains one of the most frequently diagnosed cancers. “In the past few decades, public health measures including tobacco cessation and lung cancer screening have contributed to the reduction of lung cancer incidence and improved survival in high-income countries, but lung cancer continues to be the leading cause of cancer-related deaths worldwide,” Saadia A. Faiz, MD, a member of the CHEST Physician editorial board, said in an interview.
“Further, new cancer diagnoses continue to increase in low-income countries where there may not be widespread public health initiatives and/or access to healthcare. Thus, development of a vaccine to prevent lung cancer could be very impactful,” she said.
Challenges to vaccine development include the heterogeneous nature of the disease, which may occur in smokers and nonsmokers, said Dr. Faiz. “Targeting the various molecular markers may be challenging,” she said. However, building on the success of other vaccine initiatives, such as the human papillomavirus vaccine for cervical cancer, and COVID-19 vaccines with collaboration and clinical research will ideally overcome these challenges, she added.
“The potential implications for a lung cancer vaccine are immense,” said Dr. Faiz.
A lung cancer vaccine could prevent a deadly disease, but continued efforts in risk factor reduction and lung cancer screening will also be important, she said.
“Depending on the results of this clinical research, longitudinal data regarding efficacy, side effects, and prevention will be vital prior to application in high-risk patients in clinical practice,” she emphasized.
The development of the lung cancer vaccine is supported in part by Cancer Research UK and the CRIS Cancer Foundation. Dr. Elliott has received support from Cancer Research UK but had no financial conflicts to disclose. Dr. Faiz had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Development of a , according to a press release from the University of Oxford, England.
A team of scientists from the University of Oxford, the Francis Crick Institute, and University College London (UCL) will receive funding from the Cancer Research UK and the CRIS Cancer Foundation.
The LungVax vaccine is based on technology similar to that used in the creation of the successful Oxford/AstraZeneca COVID-19 vaccine and will carry a DNA strand that trains the immune system to recognize the neoantigens that indicate abnormal lung cancer cells and then activate the immune system to kill these cells and stop the cancer, according to the statement.
Initially, scientists are working to develop a vaccine that triggers an immune response in the lab setting. If successful, the vaccine will move directly into a clinical trial. “If the subsequent early trial delivers promising results, the vaccine could then be scaled up to bigger trials for people at high risk of lung cancer,” according to the release.
Help for High-Risk Patients
Lung cancer is diagnosed in approximately 48,000 individuals in the United Kingdom each year, and the average 10-year survival is only 10%, Tim Elliott, MD, professor of immuno-oncology at the University of Oxford and lead researcher on the LungVax project, said in an interview. Nearly three-quarters of the 35,000 annual deaths are preventable by quitting smoking, which remains the best risk reduction strategy to date, he said. However, “an intervention such as a vaccine, given when people are healthy and are more likely to have a strong immune system, could benefit many thousands per year in the UK and 1.8 million patients worldwide,” he said.
Preliminary Trial Plans
The initial trial of the vaccine is a collaboration between Oxford University, UCL, and the Francis Crick Institute, Dr. Elliott said. The trial is a culmination of research into the biology and genetics of lung cancer at UCL and vaccine design research at the University of Oxford.
“We are at a very early stage of the program, which will develop over the next 6 years if all goes to plan,” said Dr. Elliott. The vaccine is designed on the basis of shared lung cancer antigens and packaged into the ChAdOx delivery system that proved successful as the Oxford-AstraZeneca COVID-19 vaccine, he said.
“We intend to vaccinate individuals who have had curative surgery for their lung cancer after being diagnosed with a very early stage of the disease,” Dr. Elliott said.
Challenges to vaccine development include knowing whether there is a clinical benefit, Dr. Elliott noted. “Our clinical trial is calculated to show up to 15% reduction in risk over 3-5 years, but only long-term follow-up will really tell us whether the immune responses we see to the vaccine within the first few weeks will have a long-term effect,” he emphasized.
In clinical practice, “these people are cancer-free and healthy after surgery,” said Dr. Elliott. However, “they are at a high risk of recurrence; 30%-70% of ex-patients will develop new cancer in their lifetime and in the majority of cases that will happen within 2 years after surgery,” he said. “We think that vaccinating them against common lung cancer antigens could reduce this risk significantly and remove some of the uncertainty that they live with after their operation.”
Vaccine Has Potential for Immense Impact
Lung cancer remains one of the most frequently diagnosed cancers. “In the past few decades, public health measures including tobacco cessation and lung cancer screening have contributed to the reduction of lung cancer incidence and improved survival in high-income countries, but lung cancer continues to be the leading cause of cancer-related deaths worldwide,” Saadia A. Faiz, MD, a member of the CHEST Physician editorial board, said in an interview.
“Further, new cancer diagnoses continue to increase in low-income countries where there may not be widespread public health initiatives and/or access to healthcare. Thus, development of a vaccine to prevent lung cancer could be very impactful,” she said.
Challenges to vaccine development include the heterogeneous nature of the disease, which may occur in smokers and nonsmokers, said Dr. Faiz. “Targeting the various molecular markers may be challenging,” she said. However, building on the success of other vaccine initiatives, such as the human papillomavirus vaccine for cervical cancer, and COVID-19 vaccines with collaboration and clinical research will ideally overcome these challenges, she added.
“The potential implications for a lung cancer vaccine are immense,” said Dr. Faiz.
A lung cancer vaccine could prevent a deadly disease, but continued efforts in risk factor reduction and lung cancer screening will also be important, she said.
“Depending on the results of this clinical research, longitudinal data regarding efficacy, side effects, and prevention will be vital prior to application in high-risk patients in clinical practice,” she emphasized.
The development of the lung cancer vaccine is supported in part by Cancer Research UK and the CRIS Cancer Foundation. Dr. Elliott has received support from Cancer Research UK but had no financial conflicts to disclose. Dr. Faiz had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Development of a , according to a press release from the University of Oxford, England.
A team of scientists from the University of Oxford, the Francis Crick Institute, and University College London (UCL) will receive funding from the Cancer Research UK and the CRIS Cancer Foundation.
The LungVax vaccine is based on technology similar to that used in the creation of the successful Oxford/AstraZeneca COVID-19 vaccine and will carry a DNA strand that trains the immune system to recognize the neoantigens that indicate abnormal lung cancer cells and then activate the immune system to kill these cells and stop the cancer, according to the statement.
Initially, scientists are working to develop a vaccine that triggers an immune response in the lab setting. If successful, the vaccine will move directly into a clinical trial. “If the subsequent early trial delivers promising results, the vaccine could then be scaled up to bigger trials for people at high risk of lung cancer,” according to the release.
Help for High-Risk Patients
Lung cancer is diagnosed in approximately 48,000 individuals in the United Kingdom each year, and the average 10-year survival is only 10%, Tim Elliott, MD, professor of immuno-oncology at the University of Oxford and lead researcher on the LungVax project, said in an interview. Nearly three-quarters of the 35,000 annual deaths are preventable by quitting smoking, which remains the best risk reduction strategy to date, he said. However, “an intervention such as a vaccine, given when people are healthy and are more likely to have a strong immune system, could benefit many thousands per year in the UK and 1.8 million patients worldwide,” he said.
Preliminary Trial Plans
The initial trial of the vaccine is a collaboration between Oxford University, UCL, and the Francis Crick Institute, Dr. Elliott said. The trial is a culmination of research into the biology and genetics of lung cancer at UCL and vaccine design research at the University of Oxford.
“We are at a very early stage of the program, which will develop over the next 6 years if all goes to plan,” said Dr. Elliott. The vaccine is designed on the basis of shared lung cancer antigens and packaged into the ChAdOx delivery system that proved successful as the Oxford-AstraZeneca COVID-19 vaccine, he said.
“We intend to vaccinate individuals who have had curative surgery for their lung cancer after being diagnosed with a very early stage of the disease,” Dr. Elliott said.
Challenges to vaccine development include knowing whether there is a clinical benefit, Dr. Elliott noted. “Our clinical trial is calculated to show up to 15% reduction in risk over 3-5 years, but only long-term follow-up will really tell us whether the immune responses we see to the vaccine within the first few weeks will have a long-term effect,” he emphasized.
In clinical practice, “these people are cancer-free and healthy after surgery,” said Dr. Elliott. However, “they are at a high risk of recurrence; 30%-70% of ex-patients will develop new cancer in their lifetime and in the majority of cases that will happen within 2 years after surgery,” he said. “We think that vaccinating them against common lung cancer antigens could reduce this risk significantly and remove some of the uncertainty that they live with after their operation.”
Vaccine Has Potential for Immense Impact
Lung cancer remains one of the most frequently diagnosed cancers. “In the past few decades, public health measures including tobacco cessation and lung cancer screening have contributed to the reduction of lung cancer incidence and improved survival in high-income countries, but lung cancer continues to be the leading cause of cancer-related deaths worldwide,” Saadia A. Faiz, MD, a member of the CHEST Physician editorial board, said in an interview.
“Further, new cancer diagnoses continue to increase in low-income countries where there may not be widespread public health initiatives and/or access to healthcare. Thus, development of a vaccine to prevent lung cancer could be very impactful,” she said.
Challenges to vaccine development include the heterogeneous nature of the disease, which may occur in smokers and nonsmokers, said Dr. Faiz. “Targeting the various molecular markers may be challenging,” she said. However, building on the success of other vaccine initiatives, such as the human papillomavirus vaccine for cervical cancer, and COVID-19 vaccines with collaboration and clinical research will ideally overcome these challenges, she added.
“The potential implications for a lung cancer vaccine are immense,” said Dr. Faiz.
A lung cancer vaccine could prevent a deadly disease, but continued efforts in risk factor reduction and lung cancer screening will also be important, she said.
“Depending on the results of this clinical research, longitudinal data regarding efficacy, side effects, and prevention will be vital prior to application in high-risk patients in clinical practice,” she emphasized.
The development of the lung cancer vaccine is supported in part by Cancer Research UK and the CRIS Cancer Foundation. Dr. Elliott has received support from Cancer Research UK but had no financial conflicts to disclose. Dr. Faiz had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Active Surveillance for Cancer Doesn’t Increase Malpractice Risk
TOPLINE:
METHODOLOGY:
- Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
- Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and or from 1990 to 2022.
- Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
- Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.
TAKEAWAY:
- Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
- In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
- The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
- No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.
IN PRACTICE:
“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”
SOURCE:
This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.
LIMITATIONS:
The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.
DISCLOSURES:
The researchers did not provide any disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
- Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and or from 1990 to 2022.
- Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
- Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.
TAKEAWAY:
- Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
- In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
- The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
- No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.
IN PRACTICE:
“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”
SOURCE:
This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.
LIMITATIONS:
The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.
DISCLOSURES:
The researchers did not provide any disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Although practice guidelines from the National Comprehensive Cancer Network consider active surveillance an effective strategy for managing low-risk cancers, some physicians have been hesitant to incorporate it into their practice because of concerns about potential litigation.
- Researchers used Westlaw Edge and LexisNexis Advance databases to identify malpractice trends involving active surveillance related to thyroid, prostate, kidney, and or from 1990 to 2022.
- Data included unpublished cases, trial orders, jury verdicts, and administrative decisions.
- Researchers identified 201 malpractice cases across all low-risk cancers in the initial screening. Out of these, only five cases, all , involved active surveillance as the point of allegation.
TAKEAWAY:
- Out of the five prostate cancer cases, two involved incarcerated patients with Gleason 6 very-low-risk prostate adenocarcinoma that was managed with active surveillance by their urologists.
- In these two cases, the patients claimed that active surveillance violated their 8th Amendment right to be free from cruel or unusual punishment. In both cases, there was no metastasis or spread detected and the court determined active surveillance management was performed under national standards.
- The other three cases involved litigation claiming that active surveillance was not explicitly recommended as a treatment option for patients who all had very-low-risk prostate adenocarcinoma and had reported negligence from an intervention ( or cryoablation). However, all cases had documented informed consent for active surveillance.
- No relevant cases were found relating to active surveillance in any other type of cancer, whether in an initial diagnosis or recurrence.
IN PRACTICE:
“This data should bolster physicians’ confidence in recommending active surveillance for their patients when it is an appropriate option,” study coauthor Timothy Daskivich, MD, assistant professor of surgery at Cedars-Sinai Medical Center, Los Angeles, said in a statement . “Active surveillance maximizes quality of life and avoids unnecessary overtreatment, and it does not increase medicolegal liability to physicians, as detailed in the case dismissals identified in this study.”
SOURCE:
This study, led by Samuel Chang, JD, with Athene Law LLP, San Francisco, was recently published in Annals of Surgery.
LIMITATIONS:
The Westlaw and Lexis databases may not contain all cases or decisions issued by a state regulatory agency, like a medical board. Federal and state decisions from lower courts may not be published and available. Also, settlements outside of court or suits filed and not pursued were not included in the data.
DISCLOSURES:
The researchers did not provide any disclosures.
A version of this article appeared on Medscape.com.
It Takes a Village: Treating Patients for NSCLC Brain Metastases
Treatment decisions about the care of patients with non–small cell lung cancer (NSCLC) that has metastasized to the brain should always be made by a multidisciplinary team, according to a lung cancer research specialist.
The care of these patients can be quite complex, and the brain is still largely terra incognita, said Lizza Hendriks, MD, PhD, during a case-based session at the European Lung Cancer Congress (ELCC) 2024 in Prague, Czech Republic.
The approach to patients with NSCLC metastatic to the brain and central nervous system was the subject of the session presented by Dr. Hendriks of Maastricht University Medical Center in Maastricht, the Netherlands. During this session, she outlined what is known, what is believed to be true, and what is still unknown about the treatment of patients with NSCLC that has spread to the CNS.
“Immunotherapy has moderate efficacy in the brain, but it can result in long-term disease control,” she said. She added that the best treatment strategy using these agents, whether immunotherapy alone or combined with chemotherapy, is still unknown, even when patients have high levels of programmed death protein 1 (PD-1) in their tumors.
“Also, we don’t know the best sequence of treatments, and we really need more preclinical research regarding the tumor microenvironment in the CNS,” she said.
Next-generation tyrosine kinase inhibitors (TKIs) generally have good intracranial efficacy, except for KRAS G12C inhibitors, which need to be tweaked for better effectiveness in the brain. The optimal sequence for TKIs also still needs to be determined, she continued.
Decision Points
Dr. Hendriks summarized decision points for the case of a 60-year-old female patient, a smoker, who in February of 2021 was evaluated for multiple asymptomatic brain metastases. The patient, who had good performance status, had a diagnosis of stage IVB NSCLC of adenocarcinoma histology, with a tumor positive for a KRAS G12C mutation and with 50% of tumor cells expressing PD-1.
The patient was treated with whole-brain radiation therapy and single-agent immunotherapy, and, 8 months later, in October 2021, was diagnosed with extracranial progressive disease and was then started on the KRAS G12c inhibitor sotorasib (Lumakras).
In May 2023 the patient was diagnosed with CNS oligoprogressive disease (that is, isolated progressing lesions) and underwent stereotactic radiotherapy. In June 2023 the patient was found to have progressive disease and was then started on platinum-based chemotherapy, with disease progression again noted in December of that year. The patient was still alive at the time of the presentation.
The first decision point in this case, Dr. Hendriks said, was whether to treat the patient at the time of diagnosis of brain metastases with upfront systemic or local therapy for the metastases.
At the time of extracranial progressive disease, should the treatment be another immumotherapy, chemotherapy, or a targeted agent?
“And the last decision is what should we do [in the event of] CNS oligoprogression?,” she said.
First Decision
For cases such as that described by Dr. Hendriks the question is whether upfront local therapy is needed if the patient is initially asymptomatic. Other considerations concerning early local therapy include the risks for late toxicities and whether there is also extracranial disease that needs to be controlled.
If systemic therapy is considered at this point, clinicians need to consider intracranial response rates to specific agents, time to onset of response, risk of pseudoprogression, and the risk of toxicity if radiotherapy is delayed until later in the disease course.
“I think all of these patients with brain metastases really deserve multidisciplinary team decisions in order to maintain or to [move] to new treatments, improve the quality of life, and improve survival,” she said.
In the case described here, the patient had small but numerous metastases that indicated the need for extracranial control, she said.
European Society of Medical Oncology (ESMO) guidelines recommend that asymptomatic patients or those with oligosymptomatic NSCLC brain metastases with an oncogenic driver receive a brain-penetrating TKI. Those with no oncogenic drive but high PD-1 expression should receive upfront immunotherapy alone, while those with PD-1 ligand 1 (PD-L1) expression below 50% receive chemoimmunotherapy.
The joint American Society of Clinical Oncology (ASCO), Society for Neuro-Oncology (SNO), and American Society for Radiation Oncology (ASTRO) guideline for treatment of brain metastases recommends a CNS-penetrating TKI for patients with asymptomatic NSCLC brain metastases bearing EGFR or ALK alterations. If there is no oncogenic driver, the guideline recommends the option of pembrolizumab (Keytruda) with or without chemotherapy.
Both the US and European guidelines recommend initiating local treatment for patients with symptomatic metastases. The level of evidence for these recommendations is low, however.
Clinicians still need better evidence about the potential for upfront immunotherapy for these patients, more information about the NSCLC brain metastases immune environment and tumor microenvironment, data on the best treatment sequence, and new strategies for improving CNS penetration of systemic therapy, Dr. Hendriks said.
Second Decision
At the time of CNS progression, the question becomes whether patients would benefit from targeted therapy or chemotherapy.
“We quite often say that chemotherapy doesn’t work in the brain, but that’s not entirely true,” Dr. Hendriks said, noting that, depending on the regimen range, brain response rates range from 23% to as high as 50% in patients with previously untreated asymptomatic brain metastases, although the median survival times are fairly low, on the order of 4 to almost 13 months.
There is also preclinical evidence that chemotherapy uptake is higher for larger brain metastases, compared with normal tissue and cerebrospinal fluid, “so the blood-brain barrier opens if you have the larger brain metastases,” she said.
KRAS-positive NSCLC is associated with a high risk for brain metastases, and these metastases share the same mutation as the primary cancer, suggesting potential efficacy of KRAS G12c inhibitors. There is preclinical evidence that adagrasib (Krazati) has CNS penetration, and there was evidence for intracranial efficacy of the drug in the KRYSTAL-1b trial, Dr. Hendriks noted.
There are fewer data for the other Food and Drug Administration (FDA)–approved inhibitor, sotorasib, but there is evidence to suggest that its brain activity is restricted by ABCB1, a gene encoding for a transporter protein that shuttles substances out of cells.
Third Decision
For patients with CNS oligoprogression, the question is whether to adapt systemic therapy or use local therapy.
There is some evidence to support dose escalation for patients with oligoprogression of tumors with EGFR or ALK alterations, but no data to support such a strategy for those with KRAS alterations, she said.
In these situations, data support dose escalation of osimertinib (Tagrisso), especially for patients with leptomeningeal disease, and brigatinib (Alunbrig), but there is very little evidence to support dose escalation for any other drugs that might be tried, she said.
In the question-and-answer part of the session, Antonin Levy, MD, from Gustave Roussy in Villejuif, France, who also presented during the session, asked Dr. Hendriks what she would recommend for a patient with a long-term response to chemoimmunotherapy for whom treatment cessation may be recommended, but who still has oligopersistent brain metastases.
“The difficulty is that with immunotherapy patients can have persistent lesions without any tumor activity, and in the brain I think there is no reliable technique to evaluate this type of thing,” she said.
Dr. Hendriks added that she would continue to follow the patient, but also closely evaluate disease progression by reviewing all scans over the course of therapy to determine whether the tumor is truly stable, follow the patient with brain imaging, and then “don’t do anything.”
Dr. Hendriks disclosed grants/research support and financial relationships with multiple companies. Dr. Levy disclosed research grants from Beigene, AstraZeneca, PharmaMar, and Roche.
Treatment decisions about the care of patients with non–small cell lung cancer (NSCLC) that has metastasized to the brain should always be made by a multidisciplinary team, according to a lung cancer research specialist.
The care of these patients can be quite complex, and the brain is still largely terra incognita, said Lizza Hendriks, MD, PhD, during a case-based session at the European Lung Cancer Congress (ELCC) 2024 in Prague, Czech Republic.
The approach to patients with NSCLC metastatic to the brain and central nervous system was the subject of the session presented by Dr. Hendriks of Maastricht University Medical Center in Maastricht, the Netherlands. During this session, she outlined what is known, what is believed to be true, and what is still unknown about the treatment of patients with NSCLC that has spread to the CNS.
“Immunotherapy has moderate efficacy in the brain, but it can result in long-term disease control,” she said. She added that the best treatment strategy using these agents, whether immunotherapy alone or combined with chemotherapy, is still unknown, even when patients have high levels of programmed death protein 1 (PD-1) in their tumors.
“Also, we don’t know the best sequence of treatments, and we really need more preclinical research regarding the tumor microenvironment in the CNS,” she said.
Next-generation tyrosine kinase inhibitors (TKIs) generally have good intracranial efficacy, except for KRAS G12C inhibitors, which need to be tweaked for better effectiveness in the brain. The optimal sequence for TKIs also still needs to be determined, she continued.
Decision Points
Dr. Hendriks summarized decision points for the case of a 60-year-old female patient, a smoker, who in February of 2021 was evaluated for multiple asymptomatic brain metastases. The patient, who had good performance status, had a diagnosis of stage IVB NSCLC of adenocarcinoma histology, with a tumor positive for a KRAS G12C mutation and with 50% of tumor cells expressing PD-1.
The patient was treated with whole-brain radiation therapy and single-agent immunotherapy, and, 8 months later, in October 2021, was diagnosed with extracranial progressive disease and was then started on the KRAS G12c inhibitor sotorasib (Lumakras).
In May 2023 the patient was diagnosed with CNS oligoprogressive disease (that is, isolated progressing lesions) and underwent stereotactic radiotherapy. In June 2023 the patient was found to have progressive disease and was then started on platinum-based chemotherapy, with disease progression again noted in December of that year. The patient was still alive at the time of the presentation.
The first decision point in this case, Dr. Hendriks said, was whether to treat the patient at the time of diagnosis of brain metastases with upfront systemic or local therapy for the metastases.
At the time of extracranial progressive disease, should the treatment be another immumotherapy, chemotherapy, or a targeted agent?
“And the last decision is what should we do [in the event of] CNS oligoprogression?,” she said.
First Decision
For cases such as that described by Dr. Hendriks the question is whether upfront local therapy is needed if the patient is initially asymptomatic. Other considerations concerning early local therapy include the risks for late toxicities and whether there is also extracranial disease that needs to be controlled.
If systemic therapy is considered at this point, clinicians need to consider intracranial response rates to specific agents, time to onset of response, risk of pseudoprogression, and the risk of toxicity if radiotherapy is delayed until later in the disease course.
“I think all of these patients with brain metastases really deserve multidisciplinary team decisions in order to maintain or to [move] to new treatments, improve the quality of life, and improve survival,” she said.
In the case described here, the patient had small but numerous metastases that indicated the need for extracranial control, she said.
European Society of Medical Oncology (ESMO) guidelines recommend that asymptomatic patients or those with oligosymptomatic NSCLC brain metastases with an oncogenic driver receive a brain-penetrating TKI. Those with no oncogenic drive but high PD-1 expression should receive upfront immunotherapy alone, while those with PD-1 ligand 1 (PD-L1) expression below 50% receive chemoimmunotherapy.
The joint American Society of Clinical Oncology (ASCO), Society for Neuro-Oncology (SNO), and American Society for Radiation Oncology (ASTRO) guideline for treatment of brain metastases recommends a CNS-penetrating TKI for patients with asymptomatic NSCLC brain metastases bearing EGFR or ALK alterations. If there is no oncogenic driver, the guideline recommends the option of pembrolizumab (Keytruda) with or without chemotherapy.
Both the US and European guidelines recommend initiating local treatment for patients with symptomatic metastases. The level of evidence for these recommendations is low, however.
Clinicians still need better evidence about the potential for upfront immunotherapy for these patients, more information about the NSCLC brain metastases immune environment and tumor microenvironment, data on the best treatment sequence, and new strategies for improving CNS penetration of systemic therapy, Dr. Hendriks said.
Second Decision
At the time of CNS progression, the question becomes whether patients would benefit from targeted therapy or chemotherapy.
“We quite often say that chemotherapy doesn’t work in the brain, but that’s not entirely true,” Dr. Hendriks said, noting that, depending on the regimen range, brain response rates range from 23% to as high as 50% in patients with previously untreated asymptomatic brain metastases, although the median survival times are fairly low, on the order of 4 to almost 13 months.
There is also preclinical evidence that chemotherapy uptake is higher for larger brain metastases, compared with normal tissue and cerebrospinal fluid, “so the blood-brain barrier opens if you have the larger brain metastases,” she said.
KRAS-positive NSCLC is associated with a high risk for brain metastases, and these metastases share the same mutation as the primary cancer, suggesting potential efficacy of KRAS G12c inhibitors. There is preclinical evidence that adagrasib (Krazati) has CNS penetration, and there was evidence for intracranial efficacy of the drug in the KRYSTAL-1b trial, Dr. Hendriks noted.
There are fewer data for the other Food and Drug Administration (FDA)–approved inhibitor, sotorasib, but there is evidence to suggest that its brain activity is restricted by ABCB1, a gene encoding for a transporter protein that shuttles substances out of cells.
Third Decision
For patients with CNS oligoprogression, the question is whether to adapt systemic therapy or use local therapy.
There is some evidence to support dose escalation for patients with oligoprogression of tumors with EGFR or ALK alterations, but no data to support such a strategy for those with KRAS alterations, she said.
In these situations, data support dose escalation of osimertinib (Tagrisso), especially for patients with leptomeningeal disease, and brigatinib (Alunbrig), but there is very little evidence to support dose escalation for any other drugs that might be tried, she said.
In the question-and-answer part of the session, Antonin Levy, MD, from Gustave Roussy in Villejuif, France, who also presented during the session, asked Dr. Hendriks what she would recommend for a patient with a long-term response to chemoimmunotherapy for whom treatment cessation may be recommended, but who still has oligopersistent brain metastases.
“The difficulty is that with immunotherapy patients can have persistent lesions without any tumor activity, and in the brain I think there is no reliable technique to evaluate this type of thing,” she said.
Dr. Hendriks added that she would continue to follow the patient, but also closely evaluate disease progression by reviewing all scans over the course of therapy to determine whether the tumor is truly stable, follow the patient with brain imaging, and then “don’t do anything.”
Dr. Hendriks disclosed grants/research support and financial relationships with multiple companies. Dr. Levy disclosed research grants from Beigene, AstraZeneca, PharmaMar, and Roche.
Treatment decisions about the care of patients with non–small cell lung cancer (NSCLC) that has metastasized to the brain should always be made by a multidisciplinary team, according to a lung cancer research specialist.
The care of these patients can be quite complex, and the brain is still largely terra incognita, said Lizza Hendriks, MD, PhD, during a case-based session at the European Lung Cancer Congress (ELCC) 2024 in Prague, Czech Republic.
The approach to patients with NSCLC metastatic to the brain and central nervous system was the subject of the session presented by Dr. Hendriks of Maastricht University Medical Center in Maastricht, the Netherlands. During this session, she outlined what is known, what is believed to be true, and what is still unknown about the treatment of patients with NSCLC that has spread to the CNS.
“Immunotherapy has moderate efficacy in the brain, but it can result in long-term disease control,” she said. She added that the best treatment strategy using these agents, whether immunotherapy alone or combined with chemotherapy, is still unknown, even when patients have high levels of programmed death protein 1 (PD-1) in their tumors.
“Also, we don’t know the best sequence of treatments, and we really need more preclinical research regarding the tumor microenvironment in the CNS,” she said.
Next-generation tyrosine kinase inhibitors (TKIs) generally have good intracranial efficacy, except for KRAS G12C inhibitors, which need to be tweaked for better effectiveness in the brain. The optimal sequence for TKIs also still needs to be determined, she continued.
Decision Points
Dr. Hendriks summarized decision points for the case of a 60-year-old female patient, a smoker, who in February of 2021 was evaluated for multiple asymptomatic brain metastases. The patient, who had good performance status, had a diagnosis of stage IVB NSCLC of adenocarcinoma histology, with a tumor positive for a KRAS G12C mutation and with 50% of tumor cells expressing PD-1.
The patient was treated with whole-brain radiation therapy and single-agent immunotherapy, and, 8 months later, in October 2021, was diagnosed with extracranial progressive disease and was then started on the KRAS G12c inhibitor sotorasib (Lumakras).
In May 2023 the patient was diagnosed with CNS oligoprogressive disease (that is, isolated progressing lesions) and underwent stereotactic radiotherapy. In June 2023 the patient was found to have progressive disease and was then started on platinum-based chemotherapy, with disease progression again noted in December of that year. The patient was still alive at the time of the presentation.
The first decision point in this case, Dr. Hendriks said, was whether to treat the patient at the time of diagnosis of brain metastases with upfront systemic or local therapy for the metastases.
At the time of extracranial progressive disease, should the treatment be another immumotherapy, chemotherapy, or a targeted agent?
“And the last decision is what should we do [in the event of] CNS oligoprogression?,” she said.
First Decision
For cases such as that described by Dr. Hendriks the question is whether upfront local therapy is needed if the patient is initially asymptomatic. Other considerations concerning early local therapy include the risks for late toxicities and whether there is also extracranial disease that needs to be controlled.
If systemic therapy is considered at this point, clinicians need to consider intracranial response rates to specific agents, time to onset of response, risk of pseudoprogression, and the risk of toxicity if radiotherapy is delayed until later in the disease course.
“I think all of these patients with brain metastases really deserve multidisciplinary team decisions in order to maintain or to [move] to new treatments, improve the quality of life, and improve survival,” she said.
In the case described here, the patient had small but numerous metastases that indicated the need for extracranial control, she said.
European Society of Medical Oncology (ESMO) guidelines recommend that asymptomatic patients or those with oligosymptomatic NSCLC brain metastases with an oncogenic driver receive a brain-penetrating TKI. Those with no oncogenic drive but high PD-1 expression should receive upfront immunotherapy alone, while those with PD-1 ligand 1 (PD-L1) expression below 50% receive chemoimmunotherapy.
The joint American Society of Clinical Oncology (ASCO), Society for Neuro-Oncology (SNO), and American Society for Radiation Oncology (ASTRO) guideline for treatment of brain metastases recommends a CNS-penetrating TKI for patients with asymptomatic NSCLC brain metastases bearing EGFR or ALK alterations. If there is no oncogenic driver, the guideline recommends the option of pembrolizumab (Keytruda) with or without chemotherapy.
Both the US and European guidelines recommend initiating local treatment for patients with symptomatic metastases. The level of evidence for these recommendations is low, however.
Clinicians still need better evidence about the potential for upfront immunotherapy for these patients, more information about the NSCLC brain metastases immune environment and tumor microenvironment, data on the best treatment sequence, and new strategies for improving CNS penetration of systemic therapy, Dr. Hendriks said.
Second Decision
At the time of CNS progression, the question becomes whether patients would benefit from targeted therapy or chemotherapy.
“We quite often say that chemotherapy doesn’t work in the brain, but that’s not entirely true,” Dr. Hendriks said, noting that, depending on the regimen range, brain response rates range from 23% to as high as 50% in patients with previously untreated asymptomatic brain metastases, although the median survival times are fairly low, on the order of 4 to almost 13 months.
There is also preclinical evidence that chemotherapy uptake is higher for larger brain metastases, compared with normal tissue and cerebrospinal fluid, “so the blood-brain barrier opens if you have the larger brain metastases,” she said.
KRAS-positive NSCLC is associated with a high risk for brain metastases, and these metastases share the same mutation as the primary cancer, suggesting potential efficacy of KRAS G12c inhibitors. There is preclinical evidence that adagrasib (Krazati) has CNS penetration, and there was evidence for intracranial efficacy of the drug in the KRYSTAL-1b trial, Dr. Hendriks noted.
There are fewer data for the other Food and Drug Administration (FDA)–approved inhibitor, sotorasib, but there is evidence to suggest that its brain activity is restricted by ABCB1, a gene encoding for a transporter protein that shuttles substances out of cells.
Third Decision
For patients with CNS oligoprogression, the question is whether to adapt systemic therapy or use local therapy.
There is some evidence to support dose escalation for patients with oligoprogression of tumors with EGFR or ALK alterations, but no data to support such a strategy for those with KRAS alterations, she said.
In these situations, data support dose escalation of osimertinib (Tagrisso), especially for patients with leptomeningeal disease, and brigatinib (Alunbrig), but there is very little evidence to support dose escalation for any other drugs that might be tried, she said.
In the question-and-answer part of the session, Antonin Levy, MD, from Gustave Roussy in Villejuif, France, who also presented during the session, asked Dr. Hendriks what she would recommend for a patient with a long-term response to chemoimmunotherapy for whom treatment cessation may be recommended, but who still has oligopersistent brain metastases.
“The difficulty is that with immunotherapy patients can have persistent lesions without any tumor activity, and in the brain I think there is no reliable technique to evaluate this type of thing,” she said.
Dr. Hendriks added that she would continue to follow the patient, but also closely evaluate disease progression by reviewing all scans over the course of therapy to determine whether the tumor is truly stable, follow the patient with brain imaging, and then “don’t do anything.”
Dr. Hendriks disclosed grants/research support and financial relationships with multiple companies. Dr. Levy disclosed research grants from Beigene, AstraZeneca, PharmaMar, and Roche.
FROM ELCC 2024
ASCO Releases Vaccination Guidelines for Adults With Cancer
TOPLINE:
“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines.
METHODOLOGY:
- “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote.
- The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts.
- The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies.
- Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies.
- The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer.
TAKEAWAY:
- The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment.
- The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT.
- After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months.
- After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines.
- Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe.
IN PRACTICE:
“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”
SOURCE:
Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.
LIMITATIONS:
The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.
DISCLOSURES:
This research had no commercial funding. Disclosures for the guideline panel are available with the original article.
A version of this article appeared on Medscape.com.
TOPLINE:
“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines.
METHODOLOGY:
- “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote.
- The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts.
- The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies.
- Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies.
- The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer.
TAKEAWAY:
- The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment.
- The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT.
- After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months.
- After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines.
- Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe.
IN PRACTICE:
“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”
SOURCE:
Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.
LIMITATIONS:
The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.
DISCLOSURES:
This research had no commercial funding. Disclosures for the guideline panel are available with the original article.
A version of this article appeared on Medscape.com.
TOPLINE:
“Optimizing vaccination status should be considered a key element in the care of patients with cancer,” according to the authors of newly released American of Clinical Oncology (ASCO) guidelines.
METHODOLOGY:
- “Infections are the second most common cause of noncancer-related mortality within the first year after a cancer diagnosis,” highlighting the need for oncologists to help ensure patients are up to date on key vaccines, an ASCO panel of experts wrote.
- The expert panel reviewed the existing evidence and made recommendations to guide vaccination of adults with solid tumors or hematologic malignancies, including those who received hematopoietic stem-cell transplantation (HSCT), chimeric antigen T-cell (CAR T-cell) therapy and B-cell-depleting therapy, as well as guide vaccination of their household contacts.
- The panel reviewed 102 publications, including 24 systematic reviews, 14 randomized controlled trials, and 64 nonrandomized studies.
- Vaccines evaluated included those for COVID-19, influenza, hepatitis A and B, respiratory syncytial virus, Tdap, human papillomavirus, inactivated polio, and rabies.
- The authors noted that patients’ underlying immune status and their cancer therapy could affect vaccination and revaccination strategies compared with recommendations for a general adult population without cancer.
TAKEAWAY:
- The first step is to determine patients’ vaccination status and ensure adults newly diagnosed with cancer (as well as their household contacts) are up to date on seasonal and age or risk-based vaccines before starting their cancer treatment. If there are gaps, patients would ideally receive their vaccinations 2-4 weeks before their cancer treatment begins; however, non-live vaccines can be given during or after treatment.
- The authors recommended complete revaccination of patients 6-12 months following HSCT to restore vaccine-induced immunity. The caveats: COVID-19, influenza, and pneumococcal vaccines can be given as early as 3 months after transplant, and patients should receive live and live attenuated vaccines only in the absence of active GVHD or immunosuppression and only ≥ 2 years following HSCT.
- After CAR T-cell therapy directed against B-cell antigens (CD19/BCMA), patients should not receive influenza and COVID-19 vaccines sooner than 3 months after completing therapy and nonlive vaccines should not be given before 6 months.
- After B-cell depleting therapy, revaccinate patients for COVID-19 only and no sooner than 6 months after completing treatment. Long-term survivors of hematologic cancer with or without active disease or those with long-standing B-cell dysfunction or hypogammaglobulinemia from therapy or B-cell lineage malignancies should receive the recommended nonlive vaccines.
- Adults with solid and hematologic cancers traveling to an area of risk should follow the CDC standard recommendations for the destination. Hepatitis A, intramuscular typhoid vaccine, inactivated polio, hepatitis B, rabies, meningococcal, and nonlive Japanese encephalitis vaccines are safe.
IN PRACTICE:
“Enhancing vaccine uptake against preventable illnesses will help the community and improve the quality of care for patients with cancer,” the authors said. “Clinicians play a critical role in helping the patient and caregiver to understand the potential benefits and risks of recommended vaccination[s]. In addition, clinicians should provide authoritative resources, such as fact-based vaccine informational handouts and Internet sites, to help patients and caregivers learn more about the topic.”
SOURCE:
Mini Kamboj, MD, with Memorial Sloan Kettering Cancer Center, New York City, and Elise Kohn, MD, with the National Cancer Institute, Rockville, Maryland, served as cochairs for the expert panel. The guideline was published March 18 in the Journal of Clinical Oncology.
LIMITATIONS:
The evidence for some vaccines in cancer patients continues to evolve, particularly for new vaccines like COVID-19 vaccines.
DISCLOSURES:
This research had no commercial funding. Disclosures for the guideline panel are available with the original article.
A version of this article appeared on Medscape.com.
Tarlatamab Shows Promise in Tackling Previously Treated SCLC
The investigational bispecific T-cell engager tarlatamab achieved durable responses and clinically meaningful survival outcomes in patients with small-cell lung cancer (SCLC), particularly at lower doses, according to a follow-up analysis of the phase 1 DeLLphi-300 trial.
Most patients with central nervous system tumors also sustained tumor shrinkage long after receiving radiotherapy, providing “encouraging evidence” of the new agent’s intracranial activity, said study presenter Horst-Dieter Hummel, MD, Comprehensive Cancer Center Mainfranken, Würzburg, Germany.
The research was presented at the European Lung Cancer Congress 2024 on March 22.
Data from the phase 1 and phase 2 DeLLphi trials, published last year, showed the compound achieved “encouraging clinical activity” in pretreated patients, said Dr. Hummel.
The initial phase 1 DeLLphi study found that after a median follow-up of 8.7 months, the immunotherapy led to a disease control rate of 51.4%, a median progression-free survival of 3.7 months, and median overall survival of 13.2 months.
At the meeting, Dr. Hummel reported longer-term outcomes from the phase 1 study over a median of 12.1 months as well as intracranial activity in patients who received clinically relevant doses of tarlatamab, defined as ≥ 10 mg.
The 152 patients included in the analysis had a median of two prior lines of therapy; 76.3% had undergone radiotherapy, and 63.2% had received immunotherapy. Liver metastases were present in 42.1% of patients, and 25.0% had brain metastases.
Doses varied among participants, with 76 patients (50.0%) receiving 100 mg, 32 (21.0%) receiving 100 mg via extended intravenous infusion, 17 (11.2%) receiving 10 mg, and 8 (5.3%) receiving 30 mg.
The overall objective response rate was 25.0%, with a median duration of response of 11.2 months. Among patients given the 10-mg dose, the objective response rate was higher, at 35.3%, as was the median duration of response, at 14.9 months.
Tarlatamab was associated with a median overall survival of 17.5 months, with 57.9% of patients alive at 12 months. Patients receiving the 10 mg dose had a better median overall survival of 20.3 months.
Of the 16 patients with analyzable central nervous system tumors, 62.5% experienced tumor shrinkage by ≥ 30% and 87.5% experienced intracranial disease control, which lasted for a median of 7.4 months.
In this follow-up study, tarlatamab demonstrated “clinically meaningful survival outcomes in patients with previously treated SCLC, particularly with the 10 mg dose,” Dr. Hummel concluded in his presentation.
No new safety signals emerged, though almost all patients did experience tarlatamab-related adverse events (94.8% for doses > 10 mg and 100% of patients with 10 mg doses). Overall, 66.4% of the total cohort experienced cytokine release syndrome of any grade, and 11.8% developed immune effector cell-associated neurotoxicity syndrome.
Discontinuation due to treatment-related adverse events occurred in 9 patients overall, and adverse events that led to dose interruption or reduction occurred in 32 patients overall.
“After many efforts at DLL3 targeting, we finally have an agent that shows activity and efficacy, and with convincing data,” said Jessica Menis, MD, a medical oncologist at the oncology department of the University Hospital of Verona, Italy, who was not involved in the study. The intracranial activity of tarlatamab “needs to be further evaluated in untreated patients,” Dr. Menis noted, because the study included only patients with stable, treated brain metastases.
And given the high rates of adverse events, Dr. Menis cautioned that adverse event management “will be a challenge.”
On X (Twitter), Tom Newsom-Davis, MBBS, PhD, a consultant in medical oncology at Chelsea and Westminster Hospital, London, said that tarlatamab is “not a straightforward drug to use,” highlighting the occurrence of cytokine release syndrome.
“But in this significantly pretreated population and in this hard-to-treat tumor type,” the rate and duration of responses seen with the extended follow-up are ‘impressive’,” he added.
DeLLphi-300, 301, and 304 were funded by Amgen Inc. Dr. Hummel declared relationships with several companies, including Amgen, Bristol Myers Squibb, AstraZeneca, Celgene, Merck, Novartis, Daiichi Sankyo, and Roche. Dr. Menis declared relationships with AstraZeneca, BMS, MSD, Roche, and Novartis.
A version of this article appeared on Medscape.com.
The investigational bispecific T-cell engager tarlatamab achieved durable responses and clinically meaningful survival outcomes in patients with small-cell lung cancer (SCLC), particularly at lower doses, according to a follow-up analysis of the phase 1 DeLLphi-300 trial.
Most patients with central nervous system tumors also sustained tumor shrinkage long after receiving radiotherapy, providing “encouraging evidence” of the new agent’s intracranial activity, said study presenter Horst-Dieter Hummel, MD, Comprehensive Cancer Center Mainfranken, Würzburg, Germany.
The research was presented at the European Lung Cancer Congress 2024 on March 22.
Data from the phase 1 and phase 2 DeLLphi trials, published last year, showed the compound achieved “encouraging clinical activity” in pretreated patients, said Dr. Hummel.
The initial phase 1 DeLLphi study found that after a median follow-up of 8.7 months, the immunotherapy led to a disease control rate of 51.4%, a median progression-free survival of 3.7 months, and median overall survival of 13.2 months.
At the meeting, Dr. Hummel reported longer-term outcomes from the phase 1 study over a median of 12.1 months as well as intracranial activity in patients who received clinically relevant doses of tarlatamab, defined as ≥ 10 mg.
The 152 patients included in the analysis had a median of two prior lines of therapy; 76.3% had undergone radiotherapy, and 63.2% had received immunotherapy. Liver metastases were present in 42.1% of patients, and 25.0% had brain metastases.
Doses varied among participants, with 76 patients (50.0%) receiving 100 mg, 32 (21.0%) receiving 100 mg via extended intravenous infusion, 17 (11.2%) receiving 10 mg, and 8 (5.3%) receiving 30 mg.
The overall objective response rate was 25.0%, with a median duration of response of 11.2 months. Among patients given the 10-mg dose, the objective response rate was higher, at 35.3%, as was the median duration of response, at 14.9 months.
Tarlatamab was associated with a median overall survival of 17.5 months, with 57.9% of patients alive at 12 months. Patients receiving the 10 mg dose had a better median overall survival of 20.3 months.
Of the 16 patients with analyzable central nervous system tumors, 62.5% experienced tumor shrinkage by ≥ 30% and 87.5% experienced intracranial disease control, which lasted for a median of 7.4 months.
In this follow-up study, tarlatamab demonstrated “clinically meaningful survival outcomes in patients with previously treated SCLC, particularly with the 10 mg dose,” Dr. Hummel concluded in his presentation.
No new safety signals emerged, though almost all patients did experience tarlatamab-related adverse events (94.8% for doses > 10 mg and 100% of patients with 10 mg doses). Overall, 66.4% of the total cohort experienced cytokine release syndrome of any grade, and 11.8% developed immune effector cell-associated neurotoxicity syndrome.
Discontinuation due to treatment-related adverse events occurred in 9 patients overall, and adverse events that led to dose interruption or reduction occurred in 32 patients overall.
“After many efforts at DLL3 targeting, we finally have an agent that shows activity and efficacy, and with convincing data,” said Jessica Menis, MD, a medical oncologist at the oncology department of the University Hospital of Verona, Italy, who was not involved in the study. The intracranial activity of tarlatamab “needs to be further evaluated in untreated patients,” Dr. Menis noted, because the study included only patients with stable, treated brain metastases.
And given the high rates of adverse events, Dr. Menis cautioned that adverse event management “will be a challenge.”
On X (Twitter), Tom Newsom-Davis, MBBS, PhD, a consultant in medical oncology at Chelsea and Westminster Hospital, London, said that tarlatamab is “not a straightforward drug to use,” highlighting the occurrence of cytokine release syndrome.
“But in this significantly pretreated population and in this hard-to-treat tumor type,” the rate and duration of responses seen with the extended follow-up are ‘impressive’,” he added.
DeLLphi-300, 301, and 304 were funded by Amgen Inc. Dr. Hummel declared relationships with several companies, including Amgen, Bristol Myers Squibb, AstraZeneca, Celgene, Merck, Novartis, Daiichi Sankyo, and Roche. Dr. Menis declared relationships with AstraZeneca, BMS, MSD, Roche, and Novartis.
A version of this article appeared on Medscape.com.
The investigational bispecific T-cell engager tarlatamab achieved durable responses and clinically meaningful survival outcomes in patients with small-cell lung cancer (SCLC), particularly at lower doses, according to a follow-up analysis of the phase 1 DeLLphi-300 trial.
Most patients with central nervous system tumors also sustained tumor shrinkage long after receiving radiotherapy, providing “encouraging evidence” of the new agent’s intracranial activity, said study presenter Horst-Dieter Hummel, MD, Comprehensive Cancer Center Mainfranken, Würzburg, Germany.
The research was presented at the European Lung Cancer Congress 2024 on March 22.
Data from the phase 1 and phase 2 DeLLphi trials, published last year, showed the compound achieved “encouraging clinical activity” in pretreated patients, said Dr. Hummel.
The initial phase 1 DeLLphi study found that after a median follow-up of 8.7 months, the immunotherapy led to a disease control rate of 51.4%, a median progression-free survival of 3.7 months, and median overall survival of 13.2 months.
At the meeting, Dr. Hummel reported longer-term outcomes from the phase 1 study over a median of 12.1 months as well as intracranial activity in patients who received clinically relevant doses of tarlatamab, defined as ≥ 10 mg.
The 152 patients included in the analysis had a median of two prior lines of therapy; 76.3% had undergone radiotherapy, and 63.2% had received immunotherapy. Liver metastases were present in 42.1% of patients, and 25.0% had brain metastases.
Doses varied among participants, with 76 patients (50.0%) receiving 100 mg, 32 (21.0%) receiving 100 mg via extended intravenous infusion, 17 (11.2%) receiving 10 mg, and 8 (5.3%) receiving 30 mg.
The overall objective response rate was 25.0%, with a median duration of response of 11.2 months. Among patients given the 10-mg dose, the objective response rate was higher, at 35.3%, as was the median duration of response, at 14.9 months.
Tarlatamab was associated with a median overall survival of 17.5 months, with 57.9% of patients alive at 12 months. Patients receiving the 10 mg dose had a better median overall survival of 20.3 months.
Of the 16 patients with analyzable central nervous system tumors, 62.5% experienced tumor shrinkage by ≥ 30% and 87.5% experienced intracranial disease control, which lasted for a median of 7.4 months.
In this follow-up study, tarlatamab demonstrated “clinically meaningful survival outcomes in patients with previously treated SCLC, particularly with the 10 mg dose,” Dr. Hummel concluded in his presentation.
No new safety signals emerged, though almost all patients did experience tarlatamab-related adverse events (94.8% for doses > 10 mg and 100% of patients with 10 mg doses). Overall, 66.4% of the total cohort experienced cytokine release syndrome of any grade, and 11.8% developed immune effector cell-associated neurotoxicity syndrome.
Discontinuation due to treatment-related adverse events occurred in 9 patients overall, and adverse events that led to dose interruption or reduction occurred in 32 patients overall.
“After many efforts at DLL3 targeting, we finally have an agent that shows activity and efficacy, and with convincing data,” said Jessica Menis, MD, a medical oncologist at the oncology department of the University Hospital of Verona, Italy, who was not involved in the study. The intracranial activity of tarlatamab “needs to be further evaluated in untreated patients,” Dr. Menis noted, because the study included only patients with stable, treated brain metastases.
And given the high rates of adverse events, Dr. Menis cautioned that adverse event management “will be a challenge.”
On X (Twitter), Tom Newsom-Davis, MBBS, PhD, a consultant in medical oncology at Chelsea and Westminster Hospital, London, said that tarlatamab is “not a straightforward drug to use,” highlighting the occurrence of cytokine release syndrome.
“But in this significantly pretreated population and in this hard-to-treat tumor type,” the rate and duration of responses seen with the extended follow-up are ‘impressive’,” he added.
DeLLphi-300, 301, and 304 were funded by Amgen Inc. Dr. Hummel declared relationships with several companies, including Amgen, Bristol Myers Squibb, AstraZeneca, Celgene, Merck, Novartis, Daiichi Sankyo, and Roche. Dr. Menis declared relationships with AstraZeneca, BMS, MSD, Roche, and Novartis.
A version of this article appeared on Medscape.com.
FROM ELCC 2024
Debate: Does ctDNA Have Role in Monitoring Tx Efficacy in Lung Cancer?
The clinical utility of circulating tumor DNA (ctDNA) for detecting minimal residual disease (MRD) and for treatment planning postoperatively was a topic of debate at the European Lung Cancer Congress 2024, held in Prague, Czech Republic.
PRO: Prognostic Value
Enriqueta Felip, MD, PhD, of Vall d’Hebron Institute of Oncology in Barcelona, Spain, argued in favor of using liquid biopsy for disease surveillance and decision making about adjuvant therapy.
“In early stage non–small cell lung cancer I think the evidence shows that pretreatment baseline ctDNA levels are clearly prognostic, and also, after surgical resection, the MRD predicts relapse, so we know that at present ctDNA and MRD are strong prognostic markers,” she said.
“I think ctDNA is useful as a noninvasive tool in both settings — at baseline pre surgery and also post surgery — to guide adjuvant therapy decision making,” she added.
Dr. Felip noted that so-called “tumor-informed” assays, such as sequencing of tumor tissue to identify mutations that can then be tracked in plasma samples, are high sensitivity methods, but have a long turnaround time, and approximately one in five patients does not have adequate tumor tissues for analysis.
In contrast, “tumor agnostic” methods rely on epigenetic features such as DNA methylation and cell-free DNA fragmentation patterns to detect tumor-derived DNA, but don’t rely on tumor tissue sample.
Dr. Felip cited a 2017 study published in Cancer Discovery showing that in patients with localized lung cancer post treatment ctDNA detection preceded radiographic progression in 72% of patients by a median of 5.2 months. In addition, the investigators found that 53% of patients had ctDNA mutation profiles that suggested they would respond favorably to tyrosine kinase inhibitors or immune checkpoint inhibitors.
She also pointed to 2022 European Society for Medical Oncology (ESMO) recommendations on the use of ctDNA in patients with cancer, which state that detection of residual tumor DNA after NSCLC therapy with curative intent is associated with a high risk of future relapse, as supported by evidence from multiple studies. The recommendation also states, however, that there is insufficient evidence to recommend ctDNA testing in routine clinical practice in the absence of evidence from prospective clinical trials.
Evidence to support a benefit of ctDNA detection for treatment planning in the adjuvant setting come from several clinical studies, Dr. Felip said. For example, in a 2020 study published in Nature Cancer, investigators found that patients with detectable ctDNA after chemoradiotherapy who had treatment consolidation with an immune checkpoint inhibitor had significantly better freedom from progression compared with patients who had detectable ctDNA but did not receive consolidation immunotherapy.
In the IMpower010 trial, patients who were ctDNA-positive post surgery and received adjuvant atezolizumab (Tecentriq) had a median disease-free survival of 19.1 months, compared with 7.9 months for patients who did not get the immune checkpoint inhibitor, further indicating the value of ctDNA in the adjuvant setting, she said.
Wrapping up her argument, Dr. Felip acknowledged that currently the negative predictive value of ctDNA/MRD is suboptimal.
“However, we have seen that high ctDNA levels pre surgery predict poor outcome, and MRD-positive following definitive therapy is strongly prognostic and has extremely high positive predictive value for recurrence,” she said.
Taken together, the evidence suggests that patients who are ctDNA-positive preoperatively should be considered for neoadjuvant chemotherapy and immune checkpoint inhibition. If ctDNA persists after neoadjuvant therapy, patients should have extensive re-staging before surgery, because their options for pathologic complete response are limited. Patients who are MRD-positive after surgery should be treated with the same therapeutic approach as for patients with metastatic disease, Dr. Felip concluded.
CON: No Data Supporting OS Benefit
Offering counterpoint to Dr. Felip’s argument, Jordi Remon Masip, MD, PhD, of Gustave Roussy cancer treatment center in Villejuif, France, said that the currently available evidence suggests that MRD helps identify a high-risk population, but that its utility in the clinic is still uncertain.
“Today, I am a believer that we need prospective clinical trials, but one of the most important points today is to elucidate if the minimal residual disease is just prognostic or whether we really can use this minimal residual disease for making treatment decisions, not only escalating [but] also de-escalating treatment strategies in early stage non–small cell lung cancer,” he said.
Risk stratification may help to identify those patients who can most benefit from intensive therapy, but it appears to be much more difficult to risk stratify patients with early stage NSCLC, he said, pointing to the International Tailored Chemotherapy Adjuvant (ITACA) trial, a phase III multicenter randomized trial comparing adjuvant pharmacogenomic-driven chemotherapy versus standard adjuvant chemotherapy in patients with completely resected stage II-IIIA NSCLC. In this study, chemotherapy customized to individual patients according to molecular diagnostic analysis after surgery did not improve overall survival outcomes.
Dr. Masip said that as a clinician he would like to have any reliable tool that could help him to decide which patients need more therapy and which can do well with less.
He agreed that MRD-positivity as signaled by ctDNA after surgery or by a tumor-informed method correlates with poor prognosis, but he noted that MRD status depends on clinical characteristics such as sex, smoking status, age, stage, tumor size, histology, and many other factors that need to be taken into account if the assay is to have value in clinical practice.
“It’s true that the minimal residual disease may capture a poor prognostic population. However, even if we apply the minimal residual disease in our daily clinical practice, we can only capture, or we can only rescue 20% of the patients with the wild type or oncogenic early stage non–small cell lung cancer,” he said.
In addition, as Dr. Felip acknowledged, the negative predictive value of MRD is not infallible, with a 63% false negative rate compared with only a 2% false-positive rate.
“Half of the patients with the recurrence of the disease have a very, very low circulating tumor DNA, and the techniques are not sensitive enough to capture this minimal residual disease,” Dr. Masip said.
It would also be a mistake to forgo giving adjuvant therapy to those patients deemed to be MRD-negative on the basis of ctDNA, given the high false-negative rates, he said.
Oncologists also have to put themselves in their patients’ shoes:
“If our patients accept that with minimal residual disease I can only improve the disease-free survival without improving the overall survival, they would accept having less toxicity but the same survival that they would if they started the treatment later, and also what would happen if the patient is randomized to no adjuvant treatment because the minimal residual disease is negative, and some months later there is a recurrence of disease?” Dr. Masip said.
“I think we need more prospective data, but we really, really need a more sensitive test to avoid or to decrease the percentage of patients with false-negative results, and also we need very motivated patients that would accept to be randomized to de-escalate treatment strategies,” he concluded.
Dr. Felip disclosed advisory or speakers bureau roles for AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffman-La Roche, Genentech, Gilead, GlaxoSmithKline, Janssen, Medical Trends, Medscape, Merck Serono, MSD, Novartis, PeerVoice, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, and Turning Point Therapeutics. She has served as a board member of Grifols. Dr. Masip disclosed research support from MSD, AstraZeneca, and Sanofi, and other financial relationships with AstraZeneca, Sanofi, Takeda Roche, and Janssen.
The clinical utility of circulating tumor DNA (ctDNA) for detecting minimal residual disease (MRD) and for treatment planning postoperatively was a topic of debate at the European Lung Cancer Congress 2024, held in Prague, Czech Republic.
PRO: Prognostic Value
Enriqueta Felip, MD, PhD, of Vall d’Hebron Institute of Oncology in Barcelona, Spain, argued in favor of using liquid biopsy for disease surveillance and decision making about adjuvant therapy.
“In early stage non–small cell lung cancer I think the evidence shows that pretreatment baseline ctDNA levels are clearly prognostic, and also, after surgical resection, the MRD predicts relapse, so we know that at present ctDNA and MRD are strong prognostic markers,” she said.
“I think ctDNA is useful as a noninvasive tool in both settings — at baseline pre surgery and also post surgery — to guide adjuvant therapy decision making,” she added.
Dr. Felip noted that so-called “tumor-informed” assays, such as sequencing of tumor tissue to identify mutations that can then be tracked in plasma samples, are high sensitivity methods, but have a long turnaround time, and approximately one in five patients does not have adequate tumor tissues for analysis.
In contrast, “tumor agnostic” methods rely on epigenetic features such as DNA methylation and cell-free DNA fragmentation patterns to detect tumor-derived DNA, but don’t rely on tumor tissue sample.
Dr. Felip cited a 2017 study published in Cancer Discovery showing that in patients with localized lung cancer post treatment ctDNA detection preceded radiographic progression in 72% of patients by a median of 5.2 months. In addition, the investigators found that 53% of patients had ctDNA mutation profiles that suggested they would respond favorably to tyrosine kinase inhibitors or immune checkpoint inhibitors.
She also pointed to 2022 European Society for Medical Oncology (ESMO) recommendations on the use of ctDNA in patients with cancer, which state that detection of residual tumor DNA after NSCLC therapy with curative intent is associated with a high risk of future relapse, as supported by evidence from multiple studies. The recommendation also states, however, that there is insufficient evidence to recommend ctDNA testing in routine clinical practice in the absence of evidence from prospective clinical trials.
Evidence to support a benefit of ctDNA detection for treatment planning in the adjuvant setting come from several clinical studies, Dr. Felip said. For example, in a 2020 study published in Nature Cancer, investigators found that patients with detectable ctDNA after chemoradiotherapy who had treatment consolidation with an immune checkpoint inhibitor had significantly better freedom from progression compared with patients who had detectable ctDNA but did not receive consolidation immunotherapy.
In the IMpower010 trial, patients who were ctDNA-positive post surgery and received adjuvant atezolizumab (Tecentriq) had a median disease-free survival of 19.1 months, compared with 7.9 months for patients who did not get the immune checkpoint inhibitor, further indicating the value of ctDNA in the adjuvant setting, she said.
Wrapping up her argument, Dr. Felip acknowledged that currently the negative predictive value of ctDNA/MRD is suboptimal.
“However, we have seen that high ctDNA levels pre surgery predict poor outcome, and MRD-positive following definitive therapy is strongly prognostic and has extremely high positive predictive value for recurrence,” she said.
Taken together, the evidence suggests that patients who are ctDNA-positive preoperatively should be considered for neoadjuvant chemotherapy and immune checkpoint inhibition. If ctDNA persists after neoadjuvant therapy, patients should have extensive re-staging before surgery, because their options for pathologic complete response are limited. Patients who are MRD-positive after surgery should be treated with the same therapeutic approach as for patients with metastatic disease, Dr. Felip concluded.
CON: No Data Supporting OS Benefit
Offering counterpoint to Dr. Felip’s argument, Jordi Remon Masip, MD, PhD, of Gustave Roussy cancer treatment center in Villejuif, France, said that the currently available evidence suggests that MRD helps identify a high-risk population, but that its utility in the clinic is still uncertain.
“Today, I am a believer that we need prospective clinical trials, but one of the most important points today is to elucidate if the minimal residual disease is just prognostic or whether we really can use this minimal residual disease for making treatment decisions, not only escalating [but] also de-escalating treatment strategies in early stage non–small cell lung cancer,” he said.
Risk stratification may help to identify those patients who can most benefit from intensive therapy, but it appears to be much more difficult to risk stratify patients with early stage NSCLC, he said, pointing to the International Tailored Chemotherapy Adjuvant (ITACA) trial, a phase III multicenter randomized trial comparing adjuvant pharmacogenomic-driven chemotherapy versus standard adjuvant chemotherapy in patients with completely resected stage II-IIIA NSCLC. In this study, chemotherapy customized to individual patients according to molecular diagnostic analysis after surgery did not improve overall survival outcomes.
Dr. Masip said that as a clinician he would like to have any reliable tool that could help him to decide which patients need more therapy and which can do well with less.
He agreed that MRD-positivity as signaled by ctDNA after surgery or by a tumor-informed method correlates with poor prognosis, but he noted that MRD status depends on clinical characteristics such as sex, smoking status, age, stage, tumor size, histology, and many other factors that need to be taken into account if the assay is to have value in clinical practice.
“It’s true that the minimal residual disease may capture a poor prognostic population. However, even if we apply the minimal residual disease in our daily clinical practice, we can only capture, or we can only rescue 20% of the patients with the wild type or oncogenic early stage non–small cell lung cancer,” he said.
In addition, as Dr. Felip acknowledged, the negative predictive value of MRD is not infallible, with a 63% false negative rate compared with only a 2% false-positive rate.
“Half of the patients with the recurrence of the disease have a very, very low circulating tumor DNA, and the techniques are not sensitive enough to capture this minimal residual disease,” Dr. Masip said.
It would also be a mistake to forgo giving adjuvant therapy to those patients deemed to be MRD-negative on the basis of ctDNA, given the high false-negative rates, he said.
Oncologists also have to put themselves in their patients’ shoes:
“If our patients accept that with minimal residual disease I can only improve the disease-free survival without improving the overall survival, they would accept having less toxicity but the same survival that they would if they started the treatment later, and also what would happen if the patient is randomized to no adjuvant treatment because the minimal residual disease is negative, and some months later there is a recurrence of disease?” Dr. Masip said.
“I think we need more prospective data, but we really, really need a more sensitive test to avoid or to decrease the percentage of patients with false-negative results, and also we need very motivated patients that would accept to be randomized to de-escalate treatment strategies,” he concluded.
Dr. Felip disclosed advisory or speakers bureau roles for AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffman-La Roche, Genentech, Gilead, GlaxoSmithKline, Janssen, Medical Trends, Medscape, Merck Serono, MSD, Novartis, PeerVoice, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, and Turning Point Therapeutics. She has served as a board member of Grifols. Dr. Masip disclosed research support from MSD, AstraZeneca, and Sanofi, and other financial relationships with AstraZeneca, Sanofi, Takeda Roche, and Janssen.
The clinical utility of circulating tumor DNA (ctDNA) for detecting minimal residual disease (MRD) and for treatment planning postoperatively was a topic of debate at the European Lung Cancer Congress 2024, held in Prague, Czech Republic.
PRO: Prognostic Value
Enriqueta Felip, MD, PhD, of Vall d’Hebron Institute of Oncology in Barcelona, Spain, argued in favor of using liquid biopsy for disease surveillance and decision making about adjuvant therapy.
“In early stage non–small cell lung cancer I think the evidence shows that pretreatment baseline ctDNA levels are clearly prognostic, and also, after surgical resection, the MRD predicts relapse, so we know that at present ctDNA and MRD are strong prognostic markers,” she said.
“I think ctDNA is useful as a noninvasive tool in both settings — at baseline pre surgery and also post surgery — to guide adjuvant therapy decision making,” she added.
Dr. Felip noted that so-called “tumor-informed” assays, such as sequencing of tumor tissue to identify mutations that can then be tracked in plasma samples, are high sensitivity methods, but have a long turnaround time, and approximately one in five patients does not have adequate tumor tissues for analysis.
In contrast, “tumor agnostic” methods rely on epigenetic features such as DNA methylation and cell-free DNA fragmentation patterns to detect tumor-derived DNA, but don’t rely on tumor tissue sample.
Dr. Felip cited a 2017 study published in Cancer Discovery showing that in patients with localized lung cancer post treatment ctDNA detection preceded radiographic progression in 72% of patients by a median of 5.2 months. In addition, the investigators found that 53% of patients had ctDNA mutation profiles that suggested they would respond favorably to tyrosine kinase inhibitors or immune checkpoint inhibitors.
She also pointed to 2022 European Society for Medical Oncology (ESMO) recommendations on the use of ctDNA in patients with cancer, which state that detection of residual tumor DNA after NSCLC therapy with curative intent is associated with a high risk of future relapse, as supported by evidence from multiple studies. The recommendation also states, however, that there is insufficient evidence to recommend ctDNA testing in routine clinical practice in the absence of evidence from prospective clinical trials.
Evidence to support a benefit of ctDNA detection for treatment planning in the adjuvant setting come from several clinical studies, Dr. Felip said. For example, in a 2020 study published in Nature Cancer, investigators found that patients with detectable ctDNA after chemoradiotherapy who had treatment consolidation with an immune checkpoint inhibitor had significantly better freedom from progression compared with patients who had detectable ctDNA but did not receive consolidation immunotherapy.
In the IMpower010 trial, patients who were ctDNA-positive post surgery and received adjuvant atezolizumab (Tecentriq) had a median disease-free survival of 19.1 months, compared with 7.9 months for patients who did not get the immune checkpoint inhibitor, further indicating the value of ctDNA in the adjuvant setting, she said.
Wrapping up her argument, Dr. Felip acknowledged that currently the negative predictive value of ctDNA/MRD is suboptimal.
“However, we have seen that high ctDNA levels pre surgery predict poor outcome, and MRD-positive following definitive therapy is strongly prognostic and has extremely high positive predictive value for recurrence,” she said.
Taken together, the evidence suggests that patients who are ctDNA-positive preoperatively should be considered for neoadjuvant chemotherapy and immune checkpoint inhibition. If ctDNA persists after neoadjuvant therapy, patients should have extensive re-staging before surgery, because their options for pathologic complete response are limited. Patients who are MRD-positive after surgery should be treated with the same therapeutic approach as for patients with metastatic disease, Dr. Felip concluded.
CON: No Data Supporting OS Benefit
Offering counterpoint to Dr. Felip’s argument, Jordi Remon Masip, MD, PhD, of Gustave Roussy cancer treatment center in Villejuif, France, said that the currently available evidence suggests that MRD helps identify a high-risk population, but that its utility in the clinic is still uncertain.
“Today, I am a believer that we need prospective clinical trials, but one of the most important points today is to elucidate if the minimal residual disease is just prognostic or whether we really can use this minimal residual disease for making treatment decisions, not only escalating [but] also de-escalating treatment strategies in early stage non–small cell lung cancer,” he said.
Risk stratification may help to identify those patients who can most benefit from intensive therapy, but it appears to be much more difficult to risk stratify patients with early stage NSCLC, he said, pointing to the International Tailored Chemotherapy Adjuvant (ITACA) trial, a phase III multicenter randomized trial comparing adjuvant pharmacogenomic-driven chemotherapy versus standard adjuvant chemotherapy in patients with completely resected stage II-IIIA NSCLC. In this study, chemotherapy customized to individual patients according to molecular diagnostic analysis after surgery did not improve overall survival outcomes.
Dr. Masip said that as a clinician he would like to have any reliable tool that could help him to decide which patients need more therapy and which can do well with less.
He agreed that MRD-positivity as signaled by ctDNA after surgery or by a tumor-informed method correlates with poor prognosis, but he noted that MRD status depends on clinical characteristics such as sex, smoking status, age, stage, tumor size, histology, and many other factors that need to be taken into account if the assay is to have value in clinical practice.
“It’s true that the minimal residual disease may capture a poor prognostic population. However, even if we apply the minimal residual disease in our daily clinical practice, we can only capture, or we can only rescue 20% of the patients with the wild type or oncogenic early stage non–small cell lung cancer,” he said.
In addition, as Dr. Felip acknowledged, the negative predictive value of MRD is not infallible, with a 63% false negative rate compared with only a 2% false-positive rate.
“Half of the patients with the recurrence of the disease have a very, very low circulating tumor DNA, and the techniques are not sensitive enough to capture this minimal residual disease,” Dr. Masip said.
It would also be a mistake to forgo giving adjuvant therapy to those patients deemed to be MRD-negative on the basis of ctDNA, given the high false-negative rates, he said.
Oncologists also have to put themselves in their patients’ shoes:
“If our patients accept that with minimal residual disease I can only improve the disease-free survival without improving the overall survival, they would accept having less toxicity but the same survival that they would if they started the treatment later, and also what would happen if the patient is randomized to no adjuvant treatment because the minimal residual disease is negative, and some months later there is a recurrence of disease?” Dr. Masip said.
“I think we need more prospective data, but we really, really need a more sensitive test to avoid or to decrease the percentage of patients with false-negative results, and also we need very motivated patients that would accept to be randomized to de-escalate treatment strategies,” he concluded.
Dr. Felip disclosed advisory or speakers bureau roles for AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffman-La Roche, Genentech, Gilead, GlaxoSmithKline, Janssen, Medical Trends, Medscape, Merck Serono, MSD, Novartis, PeerVoice, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, and Turning Point Therapeutics. She has served as a board member of Grifols. Dr. Masip disclosed research support from MSD, AstraZeneca, and Sanofi, and other financial relationships with AstraZeneca, Sanofi, Takeda Roche, and Janssen.
FROM ELCC 2024