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Tackling grief, loss in patients with advanced lung cancer
Patients with life-limiting advanced lung cancer often experience intense grief and loss.
Palliative care aims “to anticipate, prevent, and reduce suffering, promote adaptive coping, and support the best possible quality of life ... regardless of the stage of the disease or the need for other therapies,” commented Andreas Charalambous, RN, PhD, assistant professor (acting) of oncology and palliative care at the Cyprus University of Technology in Limassol, Cyprus.
He was speaking at the 2021 World Conference on Lung Cancer, where he chaired a special session entitled, “Grief and Loss in Palliative Care.”
Research shows that the use of palliative care is associated with improved quality of life and lower costs of care for patients with cancer. But a 2015 Palliative Care Survey by the National Comprehensive Cancer Network found that although the majority of leading U.S. cancer centers have inpatient palliative care services, most reported insufficient capacity to meet the demand, and that home-based palliative care services and inpatient units were much less common.
Dr. Charalambous emphasized the importance of enhancing the use and quality of palliative care services for patients with advanced lung cancer.
During the session, experts discussed an array of strategies geared towards relieving physical symptoms as well as psychological and spiritual stressors.
Physical activity: Establishing what’s possible
Grief and loss are “natural and normal” reactions to advanced cancer, commented Celia Marston, MPallCare, clinical lead for occupational therapy at Peter MacCallum Cancer Centre in Melbourne, Australia.
Patients experience feelings of loss around their independence, relationships, physical and cognitive functioning, which in turn impacts their sense of identity, daily routines, and plans for the future.
According to Ms. Marston, the rapid physical decline patients experience in the last 3 months of life is particularly “distressing,” which is why helping patients continue to perform everyday tasks is so critical.
In clinical practice, this means providing patients palliative rehabilitation focused on maintaining at least a degree of their normal physical activity, which allows them “to adjust and contend with that decline,” Ms. Marston said. It also requires understanding what is important to patients and supporting those requests.
According to Ms. Marston, optimizing patient function can help maintain or slow that rate of physical decline, or sometimes improve it. But even partial activity can be “equally if not more important” than full participation in an activity. Patients “want to be active, they want to test what they can and can’t do” and establish what is possible, she said.
Nonpharmacological approaches to symptom control
Addressing strategies to relieve physical symptoms in patients with lung cancer, Alex Molassiotis, RN, PhD, chair professor of nursing at Hong Kong Polytechnic University, explored the role nonpharmacological interventions can play.
Dr. Molassiotis highlighted the 2021 American Society of Clinical Oncology guidelines for the Management of Dyspnea in Advanced Cancer, which discuss a range of nonpharmacological strategies to manage respiratory distress, in particular. These include supplemental oxygen and noninvasive ventilation as well as breathing techniques, posture, relaxation, meditation, physical and music therapy, and acupressure or reflexology.
In a 2015 randomized controlled feasibility trial, Dr. Molassiotis explored the effectiveness of one such strategy – inspiratory muscle training – in patients with lung cancer and reported improvements in the respiratory symptom cluster of breathlessness, cough, and fatigue. A 2020 trial of breathing retraining and psychosocial support for managing dyspnea in patients with lung cancer or mesothelioma also showed the intervention improved average dyspnea, control over dyspnea, and anxiety.
However, Dr. Molassiotis cautioned, many other nonpharmacological interventions have only “limited” evidence of effectiveness, and a “stronger evidence base” is required.
Physicians should nevertheless talk to patients about their respiratory symptoms and discuss the available options, taking into account the “major impact” these symptoms have on their quality of life.
Integrating psychological strategies
More than 40% of patients with advanced nonsmall cell lung cancer experience moderate to severe death anxiety, and about one in four patients with any stage of lung cancer experience significant depression and demoralization, research shows.
During the session, Gary Rodin, MD, of the Princess Margaret Cancer Centre in Toronto, stressed the “need to intervene” and outlined approaches relevant to different stages of the disease journey.
At the onset, he said, Emotion and Symptom-Focused Engagement (EASE) can help relieve patients’ physical symptoms and traumatic stress. Those with more advanced disease can receive Meaning-Centered Psychotherapy, or Managing Cancer and Living Meaningfully (CALM), which Dr. Rodin and his colleague Sarah Hales, MD, PhD, developed. And patients at the end of life may benefit from Dignity Therapy, a short form of psychotherapy focused on helping patients find comfort and meaning in their final days.
Dr. Rodin focused on the role of CALM for those with advanced disease. CALM encompasses three to six sessions of a semi-structured intervention given over several months. The intervention focuses on four domains: 1. Symptom management and communication with healthcare providers; 2. Changes in oneself and relationships with others; 3. Spirituality, or finding a sense of meaning and purpose; and 4. Approaches to sustain hope and face mortality.
Dr. Rodin led a 2018 randomized trial comparing CALM with usual care, which showed the intervention was associated with significant reductions in depression symptoms and death anxiety in patients with advanced cancer at three and six months, as well as better patient communication and preparedness for the end of life. Patients reported that the intervention gave them “complete freedom” to communicate about themselves, their condition, and their life.
Evidence-based psychological interventions “should be offered as standard of care” to patients with lung cancer, Dr. Rodin said.
Enhancing patient-doctor communication
Having conversations early on about the goals of cancer care is particularly critical, according to Rachelle E. Bernacki, MD, director of quality initiatives, psychosocial oncology, and palliative care at the Dana-Farber Cancer Institute.
These conversations between physicians, patients, and family members give patients and loved ones time to make informed decisions, improve patients’ quality of care and satisfaction, and increase the likelihood of using hospice care, Dr. Bernacki explained.
But the reality is that these conversations don’t happen often enough. Less than one third of patients with end-stage diagnoses reported having an end-of-life discussion with their physician, and when the topic does arise, it is typically a few weeks before a patient passes away.
Moreover, these conversations “often fail to address key elements of quality discussions,” Dr. Bernacki commented.
Part of the problem is that many doctors lack the necessary training, face time constraints, or are uncertain about when or how to initiate these conversations.
Although challenging, patients want to have these discussions. Nine of 10 Americans believe doctors should talk about end-of-life issues with their patients, and 75% of older patients want to know their prognosis so they can prepare for the future, make informed medical decisions, and optimize the time they have left.
Dr. Bernacki highlighted a framework that can help clinicians have productive end-of-life conversations with patients. The Serious Illness Conversation Guide, developed by Ariadne Labs and the Dana-Farber Cancer Institute, outlines key steps, which include scheduling the conversation, delivering a prognosis, and exploring what matters to the patient. The guide also explores how to communicate effectively with patients, such as asking permission and clarifying questions as well as engaging in active listening.
Above all, Dr. Bernacki stressed that physicians should “listen more than talk” and avoid providing premature assurance when addressing the prognosis. “Many fears will arise that cannot be fixed, but talking about them makes them more bearable for the patient,” she said.
Physicians experience grief, too
Patients with advanced lung cancer are not the only ones who face loss and distress. More than half of physicians treating terminally ill patients can experience burnout, according to Sonia Oyola, MD, assistant professor of family medicine at the University of Chicago Medicine.
In her presentation, Dr. Oyola highlighted strategies physicians can use to manage their grief.
The first step is simply acknowledging feelings of loss. But every physician will have a “unique way of grieving and caring for themselves,” she said.
In general, the literature supports several approaches for managing grief: engaging in death talks and self-attunement or personal awareness training as well as providing end-of-life education in medical schools.
On the personal awareness front, Dr. Oyola highlighted a narrative medicine exercise where physicians write about the patient and reflect on what moved or touched them, what surprised them, and what inspired them.
Pursuing this kind of exercise allows physicians to reflect on their experiences in a way “we often do not have the opportunity to do” and could prevent some of the “devastating consequences in our practices, such as burnout,” Dr. Oyola said.
No funding declared. Dr. Molassiotis has reported a relationship with Helsinn. No other relevant financial relationships declared.
A version of this article first appeared on Medscape.com.
Patients with life-limiting advanced lung cancer often experience intense grief and loss.
Palliative care aims “to anticipate, prevent, and reduce suffering, promote adaptive coping, and support the best possible quality of life ... regardless of the stage of the disease or the need for other therapies,” commented Andreas Charalambous, RN, PhD, assistant professor (acting) of oncology and palliative care at the Cyprus University of Technology in Limassol, Cyprus.
He was speaking at the 2021 World Conference on Lung Cancer, where he chaired a special session entitled, “Grief and Loss in Palliative Care.”
Research shows that the use of palliative care is associated with improved quality of life and lower costs of care for patients with cancer. But a 2015 Palliative Care Survey by the National Comprehensive Cancer Network found that although the majority of leading U.S. cancer centers have inpatient palliative care services, most reported insufficient capacity to meet the demand, and that home-based palliative care services and inpatient units were much less common.
Dr. Charalambous emphasized the importance of enhancing the use and quality of palliative care services for patients with advanced lung cancer.
During the session, experts discussed an array of strategies geared towards relieving physical symptoms as well as psychological and spiritual stressors.
Physical activity: Establishing what’s possible
Grief and loss are “natural and normal” reactions to advanced cancer, commented Celia Marston, MPallCare, clinical lead for occupational therapy at Peter MacCallum Cancer Centre in Melbourne, Australia.
Patients experience feelings of loss around their independence, relationships, physical and cognitive functioning, which in turn impacts their sense of identity, daily routines, and plans for the future.
According to Ms. Marston, the rapid physical decline patients experience in the last 3 months of life is particularly “distressing,” which is why helping patients continue to perform everyday tasks is so critical.
In clinical practice, this means providing patients palliative rehabilitation focused on maintaining at least a degree of their normal physical activity, which allows them “to adjust and contend with that decline,” Ms. Marston said. It also requires understanding what is important to patients and supporting those requests.
According to Ms. Marston, optimizing patient function can help maintain or slow that rate of physical decline, or sometimes improve it. But even partial activity can be “equally if not more important” than full participation in an activity. Patients “want to be active, they want to test what they can and can’t do” and establish what is possible, she said.
Nonpharmacological approaches to symptom control
Addressing strategies to relieve physical symptoms in patients with lung cancer, Alex Molassiotis, RN, PhD, chair professor of nursing at Hong Kong Polytechnic University, explored the role nonpharmacological interventions can play.
Dr. Molassiotis highlighted the 2021 American Society of Clinical Oncology guidelines for the Management of Dyspnea in Advanced Cancer, which discuss a range of nonpharmacological strategies to manage respiratory distress, in particular. These include supplemental oxygen and noninvasive ventilation as well as breathing techniques, posture, relaxation, meditation, physical and music therapy, and acupressure or reflexology.
In a 2015 randomized controlled feasibility trial, Dr. Molassiotis explored the effectiveness of one such strategy – inspiratory muscle training – in patients with lung cancer and reported improvements in the respiratory symptom cluster of breathlessness, cough, and fatigue. A 2020 trial of breathing retraining and psychosocial support for managing dyspnea in patients with lung cancer or mesothelioma also showed the intervention improved average dyspnea, control over dyspnea, and anxiety.
However, Dr. Molassiotis cautioned, many other nonpharmacological interventions have only “limited” evidence of effectiveness, and a “stronger evidence base” is required.
Physicians should nevertheless talk to patients about their respiratory symptoms and discuss the available options, taking into account the “major impact” these symptoms have on their quality of life.
Integrating psychological strategies
More than 40% of patients with advanced nonsmall cell lung cancer experience moderate to severe death anxiety, and about one in four patients with any stage of lung cancer experience significant depression and demoralization, research shows.
During the session, Gary Rodin, MD, of the Princess Margaret Cancer Centre in Toronto, stressed the “need to intervene” and outlined approaches relevant to different stages of the disease journey.
At the onset, he said, Emotion and Symptom-Focused Engagement (EASE) can help relieve patients’ physical symptoms and traumatic stress. Those with more advanced disease can receive Meaning-Centered Psychotherapy, or Managing Cancer and Living Meaningfully (CALM), which Dr. Rodin and his colleague Sarah Hales, MD, PhD, developed. And patients at the end of life may benefit from Dignity Therapy, a short form of psychotherapy focused on helping patients find comfort and meaning in their final days.
Dr. Rodin focused on the role of CALM for those with advanced disease. CALM encompasses three to six sessions of a semi-structured intervention given over several months. The intervention focuses on four domains: 1. Symptom management and communication with healthcare providers; 2. Changes in oneself and relationships with others; 3. Spirituality, or finding a sense of meaning and purpose; and 4. Approaches to sustain hope and face mortality.
Dr. Rodin led a 2018 randomized trial comparing CALM with usual care, which showed the intervention was associated with significant reductions in depression symptoms and death anxiety in patients with advanced cancer at three and six months, as well as better patient communication and preparedness for the end of life. Patients reported that the intervention gave them “complete freedom” to communicate about themselves, their condition, and their life.
Evidence-based psychological interventions “should be offered as standard of care” to patients with lung cancer, Dr. Rodin said.
Enhancing patient-doctor communication
Having conversations early on about the goals of cancer care is particularly critical, according to Rachelle E. Bernacki, MD, director of quality initiatives, psychosocial oncology, and palliative care at the Dana-Farber Cancer Institute.
These conversations between physicians, patients, and family members give patients and loved ones time to make informed decisions, improve patients’ quality of care and satisfaction, and increase the likelihood of using hospice care, Dr. Bernacki explained.
But the reality is that these conversations don’t happen often enough. Less than one third of patients with end-stage diagnoses reported having an end-of-life discussion with their physician, and when the topic does arise, it is typically a few weeks before a patient passes away.
Moreover, these conversations “often fail to address key elements of quality discussions,” Dr. Bernacki commented.
Part of the problem is that many doctors lack the necessary training, face time constraints, or are uncertain about when or how to initiate these conversations.
Although challenging, patients want to have these discussions. Nine of 10 Americans believe doctors should talk about end-of-life issues with their patients, and 75% of older patients want to know their prognosis so they can prepare for the future, make informed medical decisions, and optimize the time they have left.
Dr. Bernacki highlighted a framework that can help clinicians have productive end-of-life conversations with patients. The Serious Illness Conversation Guide, developed by Ariadne Labs and the Dana-Farber Cancer Institute, outlines key steps, which include scheduling the conversation, delivering a prognosis, and exploring what matters to the patient. The guide also explores how to communicate effectively with patients, such as asking permission and clarifying questions as well as engaging in active listening.
Above all, Dr. Bernacki stressed that physicians should “listen more than talk” and avoid providing premature assurance when addressing the prognosis. “Many fears will arise that cannot be fixed, but talking about them makes them more bearable for the patient,” she said.
Physicians experience grief, too
Patients with advanced lung cancer are not the only ones who face loss and distress. More than half of physicians treating terminally ill patients can experience burnout, according to Sonia Oyola, MD, assistant professor of family medicine at the University of Chicago Medicine.
In her presentation, Dr. Oyola highlighted strategies physicians can use to manage their grief.
The first step is simply acknowledging feelings of loss. But every physician will have a “unique way of grieving and caring for themselves,” she said.
In general, the literature supports several approaches for managing grief: engaging in death talks and self-attunement or personal awareness training as well as providing end-of-life education in medical schools.
On the personal awareness front, Dr. Oyola highlighted a narrative medicine exercise where physicians write about the patient and reflect on what moved or touched them, what surprised them, and what inspired them.
Pursuing this kind of exercise allows physicians to reflect on their experiences in a way “we often do not have the opportunity to do” and could prevent some of the “devastating consequences in our practices, such as burnout,” Dr. Oyola said.
No funding declared. Dr. Molassiotis has reported a relationship with Helsinn. No other relevant financial relationships declared.
A version of this article first appeared on Medscape.com.
Patients with life-limiting advanced lung cancer often experience intense grief and loss.
Palliative care aims “to anticipate, prevent, and reduce suffering, promote adaptive coping, and support the best possible quality of life ... regardless of the stage of the disease or the need for other therapies,” commented Andreas Charalambous, RN, PhD, assistant professor (acting) of oncology and palliative care at the Cyprus University of Technology in Limassol, Cyprus.
He was speaking at the 2021 World Conference on Lung Cancer, where he chaired a special session entitled, “Grief and Loss in Palliative Care.”
Research shows that the use of palliative care is associated with improved quality of life and lower costs of care for patients with cancer. But a 2015 Palliative Care Survey by the National Comprehensive Cancer Network found that although the majority of leading U.S. cancer centers have inpatient palliative care services, most reported insufficient capacity to meet the demand, and that home-based palliative care services and inpatient units were much less common.
Dr. Charalambous emphasized the importance of enhancing the use and quality of palliative care services for patients with advanced lung cancer.
During the session, experts discussed an array of strategies geared towards relieving physical symptoms as well as psychological and spiritual stressors.
Physical activity: Establishing what’s possible
Grief and loss are “natural and normal” reactions to advanced cancer, commented Celia Marston, MPallCare, clinical lead for occupational therapy at Peter MacCallum Cancer Centre in Melbourne, Australia.
Patients experience feelings of loss around their independence, relationships, physical and cognitive functioning, which in turn impacts their sense of identity, daily routines, and plans for the future.
According to Ms. Marston, the rapid physical decline patients experience in the last 3 months of life is particularly “distressing,” which is why helping patients continue to perform everyday tasks is so critical.
In clinical practice, this means providing patients palliative rehabilitation focused on maintaining at least a degree of their normal physical activity, which allows them “to adjust and contend with that decline,” Ms. Marston said. It also requires understanding what is important to patients and supporting those requests.
According to Ms. Marston, optimizing patient function can help maintain or slow that rate of physical decline, or sometimes improve it. But even partial activity can be “equally if not more important” than full participation in an activity. Patients “want to be active, they want to test what they can and can’t do” and establish what is possible, she said.
Nonpharmacological approaches to symptom control
Addressing strategies to relieve physical symptoms in patients with lung cancer, Alex Molassiotis, RN, PhD, chair professor of nursing at Hong Kong Polytechnic University, explored the role nonpharmacological interventions can play.
Dr. Molassiotis highlighted the 2021 American Society of Clinical Oncology guidelines for the Management of Dyspnea in Advanced Cancer, which discuss a range of nonpharmacological strategies to manage respiratory distress, in particular. These include supplemental oxygen and noninvasive ventilation as well as breathing techniques, posture, relaxation, meditation, physical and music therapy, and acupressure or reflexology.
In a 2015 randomized controlled feasibility trial, Dr. Molassiotis explored the effectiveness of one such strategy – inspiratory muscle training – in patients with lung cancer and reported improvements in the respiratory symptom cluster of breathlessness, cough, and fatigue. A 2020 trial of breathing retraining and psychosocial support for managing dyspnea in patients with lung cancer or mesothelioma also showed the intervention improved average dyspnea, control over dyspnea, and anxiety.
However, Dr. Molassiotis cautioned, many other nonpharmacological interventions have only “limited” evidence of effectiveness, and a “stronger evidence base” is required.
Physicians should nevertheless talk to patients about their respiratory symptoms and discuss the available options, taking into account the “major impact” these symptoms have on their quality of life.
Integrating psychological strategies
More than 40% of patients with advanced nonsmall cell lung cancer experience moderate to severe death anxiety, and about one in four patients with any stage of lung cancer experience significant depression and demoralization, research shows.
During the session, Gary Rodin, MD, of the Princess Margaret Cancer Centre in Toronto, stressed the “need to intervene” and outlined approaches relevant to different stages of the disease journey.
At the onset, he said, Emotion and Symptom-Focused Engagement (EASE) can help relieve patients’ physical symptoms and traumatic stress. Those with more advanced disease can receive Meaning-Centered Psychotherapy, or Managing Cancer and Living Meaningfully (CALM), which Dr. Rodin and his colleague Sarah Hales, MD, PhD, developed. And patients at the end of life may benefit from Dignity Therapy, a short form of psychotherapy focused on helping patients find comfort and meaning in their final days.
Dr. Rodin focused on the role of CALM for those with advanced disease. CALM encompasses three to six sessions of a semi-structured intervention given over several months. The intervention focuses on four domains: 1. Symptom management and communication with healthcare providers; 2. Changes in oneself and relationships with others; 3. Spirituality, or finding a sense of meaning and purpose; and 4. Approaches to sustain hope and face mortality.
Dr. Rodin led a 2018 randomized trial comparing CALM with usual care, which showed the intervention was associated with significant reductions in depression symptoms and death anxiety in patients with advanced cancer at three and six months, as well as better patient communication and preparedness for the end of life. Patients reported that the intervention gave them “complete freedom” to communicate about themselves, their condition, and their life.
Evidence-based psychological interventions “should be offered as standard of care” to patients with lung cancer, Dr. Rodin said.
Enhancing patient-doctor communication
Having conversations early on about the goals of cancer care is particularly critical, according to Rachelle E. Bernacki, MD, director of quality initiatives, psychosocial oncology, and palliative care at the Dana-Farber Cancer Institute.
These conversations between physicians, patients, and family members give patients and loved ones time to make informed decisions, improve patients’ quality of care and satisfaction, and increase the likelihood of using hospice care, Dr. Bernacki explained.
But the reality is that these conversations don’t happen often enough. Less than one third of patients with end-stage diagnoses reported having an end-of-life discussion with their physician, and when the topic does arise, it is typically a few weeks before a patient passes away.
Moreover, these conversations “often fail to address key elements of quality discussions,” Dr. Bernacki commented.
Part of the problem is that many doctors lack the necessary training, face time constraints, or are uncertain about when or how to initiate these conversations.
Although challenging, patients want to have these discussions. Nine of 10 Americans believe doctors should talk about end-of-life issues with their patients, and 75% of older patients want to know their prognosis so they can prepare for the future, make informed medical decisions, and optimize the time they have left.
Dr. Bernacki highlighted a framework that can help clinicians have productive end-of-life conversations with patients. The Serious Illness Conversation Guide, developed by Ariadne Labs and the Dana-Farber Cancer Institute, outlines key steps, which include scheduling the conversation, delivering a prognosis, and exploring what matters to the patient. The guide also explores how to communicate effectively with patients, such as asking permission and clarifying questions as well as engaging in active listening.
Above all, Dr. Bernacki stressed that physicians should “listen more than talk” and avoid providing premature assurance when addressing the prognosis. “Many fears will arise that cannot be fixed, but talking about them makes them more bearable for the patient,” she said.
Physicians experience grief, too
Patients with advanced lung cancer are not the only ones who face loss and distress. More than half of physicians treating terminally ill patients can experience burnout, according to Sonia Oyola, MD, assistant professor of family medicine at the University of Chicago Medicine.
In her presentation, Dr. Oyola highlighted strategies physicians can use to manage their grief.
The first step is simply acknowledging feelings of loss. But every physician will have a “unique way of grieving and caring for themselves,” she said.
In general, the literature supports several approaches for managing grief: engaging in death talks and self-attunement or personal awareness training as well as providing end-of-life education in medical schools.
On the personal awareness front, Dr. Oyola highlighted a narrative medicine exercise where physicians write about the patient and reflect on what moved or touched them, what surprised them, and what inspired them.
Pursuing this kind of exercise allows physicians to reflect on their experiences in a way “we often do not have the opportunity to do” and could prevent some of the “devastating consequences in our practices, such as burnout,” Dr. Oyola said.
No funding declared. Dr. Molassiotis has reported a relationship with Helsinn. No other relevant financial relationships declared.
A version of this article first appeared on Medscape.com.
ESMO 2021: Impressive clinical research despite pandemic
The meeting, which will be held online from September 16 to 21, will also see headlining results from immunotherapy trials in melanoma, lung cancer, and prostate cancer, as well as studies of the impact of COVID-19 vaccination in cancer patients.
“This is the second year of the virtual ESMO meeting, and this is important because the pandemic and the lockdown have impacted our clinical practice and research,” said conference press spokesman Antonio Passaro, MD, PhD, from the Division of Thoracic Oncology at the European Institute of Oncology, in Milan.
“But when you look at the submitted abstracts and the data that will be presented during ESMO, we can see that clinical research has been ‘resurrected,’“ he told this news organization.
A huge amount of “high-quality” data will be presented, said Dr. Passaro, which is “important,” inasmuch as this is the second year of the pandemic.
He underlined that it is “crucial” to remember that “the pandemic affected not only the lives and quality of life of our patients but also health care systems and the work and quality of life of health care professionals.”
A large amount of the new clinical data to be presented at the meeting will focus on the role of immune checkpoint inhibitors in various types of cancer, Dr. Passaro commented. Many of these will be featured in the three Presidential Symposia that will be held on Saturday, Sunday, and Monday.
These include KEYNOTE-716, a trial comparing the adjuvant use of pembrolizumab (Keytruda) to placebo after complete resection of high-risk stage II melanoma (abstract LBA3), and an analysis of the IMpower010 trial that will investigate the sites of relapse and subsequent therapy with atezolizumab (Tecentriq) in comparison with best supportive care after adjuvant chemotherapy in stage IB-IIIA non–small cell lung cancer (abstract LBA9).
Dr. Passaro commented that it is “interesting to note” that the immunotherapy data at ESMO 2021 will not only be in these “classical diseases in which immunotherapy improves survival” but also in different types of cancer, thus “widening the opportunity for our patients” to benefit.
There will be “important results” for immune checkpoint inhibitors for gynecologic cancers, as well as colorectal and gastric cancers, “which is a key topic for this ESMO meeting,” he said.
Other highlights from the Presidential Symposia include the following:
- Results from the phase 3 KEYNOTE-826 study of pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer (abstract LBA2_PR)
- Results from the CheckMate 649 study, which examined nivolumab (Opdivo) plus chemotherapy or ipilimumab (Yervoy) in comparison with chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (abstract LBA7)
- Results from KRYSTAL-1, a phase 1/2 trial of the investigational agent adagrasib (MRTX849, Mirati Therapeutics) as monotherapy or combined with cetuximab for patients with colorectal cancer harboring a KRASG12C mutation (abstract LBA6)
- Data from FIRSTMAPPP, the first international randomized study of malignant progressive pheochromocytoma and paragangliomas comparing sunitinib (Sutent) with placebo (abstract 567O_PR)
- A combined analysis from the STAMPEDE protocol comparing androgen-deprivation therapy (ADT) alone to abiraterone acetate plus prednisolone, with or without enzalutamide, added to ADT for men with high-risk nonmetastatic prostate cancer (abstract LBA4_PR)
- Results from later-stage disease in men with de novo metastatic castration-sensitive prostate cancer enrolled in PEACE-1, a phase 3 trial investigating overall survival with abiraterone acetate plus prednisone (abstract LBA5_PR)
In addition, Dr. Passaro noted that data will be presented on the impact of the COVID-19 pandemic on cancer patients, as well as “interesting results” on the effect of COVID-19 vaccination on patients and their treatment, which is “crucial for all of us” to know. For example, the CAPTURE substudy of the TRACERx Renal trial will examine adaptive immunity to SARS-CoV-2 infection and vaccination in cancer patients (abstract 1557O).
Also in the same session, data will be presented from the VOICE study on vaccination against SARS-CoV-2 in patients receiving chemotherapy, immunotherapy, or chemo-immunotherapy for solid tumors (abstract LBA8).
At a press conference held ahead of the meeting, Pasi A. Jänne, MD, PhD, from the Dana Farber Cancer Center, Boston, who is the scientific co-chair of ESMO 2021, highlighted precision medicine as a key theme of the meeting.
He said that this is something the oncology community is “actively implementing worldwide to continue to make progress in cancer therapies and as such improve the outcomes of our patients.”
A version of this article first appeared on Medscape.com.
The meeting, which will be held online from September 16 to 21, will also see headlining results from immunotherapy trials in melanoma, lung cancer, and prostate cancer, as well as studies of the impact of COVID-19 vaccination in cancer patients.
“This is the second year of the virtual ESMO meeting, and this is important because the pandemic and the lockdown have impacted our clinical practice and research,” said conference press spokesman Antonio Passaro, MD, PhD, from the Division of Thoracic Oncology at the European Institute of Oncology, in Milan.
“But when you look at the submitted abstracts and the data that will be presented during ESMO, we can see that clinical research has been ‘resurrected,’“ he told this news organization.
A huge amount of “high-quality” data will be presented, said Dr. Passaro, which is “important,” inasmuch as this is the second year of the pandemic.
He underlined that it is “crucial” to remember that “the pandemic affected not only the lives and quality of life of our patients but also health care systems and the work and quality of life of health care professionals.”
A large amount of the new clinical data to be presented at the meeting will focus on the role of immune checkpoint inhibitors in various types of cancer, Dr. Passaro commented. Many of these will be featured in the three Presidential Symposia that will be held on Saturday, Sunday, and Monday.
These include KEYNOTE-716, a trial comparing the adjuvant use of pembrolizumab (Keytruda) to placebo after complete resection of high-risk stage II melanoma (abstract LBA3), and an analysis of the IMpower010 trial that will investigate the sites of relapse and subsequent therapy with atezolizumab (Tecentriq) in comparison with best supportive care after adjuvant chemotherapy in stage IB-IIIA non–small cell lung cancer (abstract LBA9).
Dr. Passaro commented that it is “interesting to note” that the immunotherapy data at ESMO 2021 will not only be in these “classical diseases in which immunotherapy improves survival” but also in different types of cancer, thus “widening the opportunity for our patients” to benefit.
There will be “important results” for immune checkpoint inhibitors for gynecologic cancers, as well as colorectal and gastric cancers, “which is a key topic for this ESMO meeting,” he said.
Other highlights from the Presidential Symposia include the following:
- Results from the phase 3 KEYNOTE-826 study of pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer (abstract LBA2_PR)
- Results from the CheckMate 649 study, which examined nivolumab (Opdivo) plus chemotherapy or ipilimumab (Yervoy) in comparison with chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (abstract LBA7)
- Results from KRYSTAL-1, a phase 1/2 trial of the investigational agent adagrasib (MRTX849, Mirati Therapeutics) as monotherapy or combined with cetuximab for patients with colorectal cancer harboring a KRASG12C mutation (abstract LBA6)
- Data from FIRSTMAPPP, the first international randomized study of malignant progressive pheochromocytoma and paragangliomas comparing sunitinib (Sutent) with placebo (abstract 567O_PR)
- A combined analysis from the STAMPEDE protocol comparing androgen-deprivation therapy (ADT) alone to abiraterone acetate plus prednisolone, with or without enzalutamide, added to ADT for men with high-risk nonmetastatic prostate cancer (abstract LBA4_PR)
- Results from later-stage disease in men with de novo metastatic castration-sensitive prostate cancer enrolled in PEACE-1, a phase 3 trial investigating overall survival with abiraterone acetate plus prednisone (abstract LBA5_PR)
In addition, Dr. Passaro noted that data will be presented on the impact of the COVID-19 pandemic on cancer patients, as well as “interesting results” on the effect of COVID-19 vaccination on patients and their treatment, which is “crucial for all of us” to know. For example, the CAPTURE substudy of the TRACERx Renal trial will examine adaptive immunity to SARS-CoV-2 infection and vaccination in cancer patients (abstract 1557O).
Also in the same session, data will be presented from the VOICE study on vaccination against SARS-CoV-2 in patients receiving chemotherapy, immunotherapy, or chemo-immunotherapy for solid tumors (abstract LBA8).
At a press conference held ahead of the meeting, Pasi A. Jänne, MD, PhD, from the Dana Farber Cancer Center, Boston, who is the scientific co-chair of ESMO 2021, highlighted precision medicine as a key theme of the meeting.
He said that this is something the oncology community is “actively implementing worldwide to continue to make progress in cancer therapies and as such improve the outcomes of our patients.”
A version of this article first appeared on Medscape.com.
The meeting, which will be held online from September 16 to 21, will also see headlining results from immunotherapy trials in melanoma, lung cancer, and prostate cancer, as well as studies of the impact of COVID-19 vaccination in cancer patients.
“This is the second year of the virtual ESMO meeting, and this is important because the pandemic and the lockdown have impacted our clinical practice and research,” said conference press spokesman Antonio Passaro, MD, PhD, from the Division of Thoracic Oncology at the European Institute of Oncology, in Milan.
“But when you look at the submitted abstracts and the data that will be presented during ESMO, we can see that clinical research has been ‘resurrected,’“ he told this news organization.
A huge amount of “high-quality” data will be presented, said Dr. Passaro, which is “important,” inasmuch as this is the second year of the pandemic.
He underlined that it is “crucial” to remember that “the pandemic affected not only the lives and quality of life of our patients but also health care systems and the work and quality of life of health care professionals.”
A large amount of the new clinical data to be presented at the meeting will focus on the role of immune checkpoint inhibitors in various types of cancer, Dr. Passaro commented. Many of these will be featured in the three Presidential Symposia that will be held on Saturday, Sunday, and Monday.
These include KEYNOTE-716, a trial comparing the adjuvant use of pembrolizumab (Keytruda) to placebo after complete resection of high-risk stage II melanoma (abstract LBA3), and an analysis of the IMpower010 trial that will investigate the sites of relapse and subsequent therapy with atezolizumab (Tecentriq) in comparison with best supportive care after adjuvant chemotherapy in stage IB-IIIA non–small cell lung cancer (abstract LBA9).
Dr. Passaro commented that it is “interesting to note” that the immunotherapy data at ESMO 2021 will not only be in these “classical diseases in which immunotherapy improves survival” but also in different types of cancer, thus “widening the opportunity for our patients” to benefit.
There will be “important results” for immune checkpoint inhibitors for gynecologic cancers, as well as colorectal and gastric cancers, “which is a key topic for this ESMO meeting,” he said.
Other highlights from the Presidential Symposia include the following:
- Results from the phase 3 KEYNOTE-826 study of pembrolizumab plus chemotherapy versus placebo plus chemotherapy for persistent, recurrent, or metastatic cervical cancer (abstract LBA2_PR)
- Results from the CheckMate 649 study, which examined nivolumab (Opdivo) plus chemotherapy or ipilimumab (Yervoy) in comparison with chemotherapy as first-line treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (abstract LBA7)
- Results from KRYSTAL-1, a phase 1/2 trial of the investigational agent adagrasib (MRTX849, Mirati Therapeutics) as monotherapy or combined with cetuximab for patients with colorectal cancer harboring a KRASG12C mutation (abstract LBA6)
- Data from FIRSTMAPPP, the first international randomized study of malignant progressive pheochromocytoma and paragangliomas comparing sunitinib (Sutent) with placebo (abstract 567O_PR)
- A combined analysis from the STAMPEDE protocol comparing androgen-deprivation therapy (ADT) alone to abiraterone acetate plus prednisolone, with or without enzalutamide, added to ADT for men with high-risk nonmetastatic prostate cancer (abstract LBA4_PR)
- Results from later-stage disease in men with de novo metastatic castration-sensitive prostate cancer enrolled in PEACE-1, a phase 3 trial investigating overall survival with abiraterone acetate plus prednisone (abstract LBA5_PR)
In addition, Dr. Passaro noted that data will be presented on the impact of the COVID-19 pandemic on cancer patients, as well as “interesting results” on the effect of COVID-19 vaccination on patients and their treatment, which is “crucial for all of us” to know. For example, the CAPTURE substudy of the TRACERx Renal trial will examine adaptive immunity to SARS-CoV-2 infection and vaccination in cancer patients (abstract 1557O).
Also in the same session, data will be presented from the VOICE study on vaccination against SARS-CoV-2 in patients receiving chemotherapy, immunotherapy, or chemo-immunotherapy for solid tumors (abstract LBA8).
At a press conference held ahead of the meeting, Pasi A. Jänne, MD, PhD, from the Dana Farber Cancer Center, Boston, who is the scientific co-chair of ESMO 2021, highlighted precision medicine as a key theme of the meeting.
He said that this is something the oncology community is “actively implementing worldwide to continue to make progress in cancer therapies and as such improve the outcomes of our patients.”
A version of this article first appeared on Medscape.com.
POSEIDON: Two ICIs plus chemo up survival in mNSCLC
The study involved over 1,000 patients with stage IV NSCLC. Participants were randomly assigned to receive either two ICIs (tremelimumab and durvalumab [Imfinzi]) plus chemotherapy, or one immunotherapy (durvalumab) plus chemotherapy, or chemotherapy alone.
Adding durvalumab to chemotherapy significantly improved PFS by 26% but did not significantly improve OS, the researchers reported. However, adding both tremelimumab and durvalumab significantly increased both PFS (by 28%) and OS (by 23%). Median OS was 14.0 months versus 11.7 months for chemotherapy.
The results were presented on Sept. 9 at a presidential symposium of the World Conference on Lung Cancer 2021.
The two immunotherapies act at different immune checkpoints – tremelimumab acts at CTLA-4, and durvalumab acts at programmed death–1/PD–ligand 1 (PD-L1). Both drugs are from AstraZeneca, which sponsored the POSEIDON trial.
With no new safety signals identified, the triple therapy combination “represents a potential new frontline treatment option for metastatic non–small cell lung cancer,” said lead researcher Melissa L. Johnson, MD, from the Sarah Cannon Research Institute, Nashville, Tenn.
Reacting to the new results in a discussion of the paper, Julie R. Brahmer, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, said that, with so many first-line treatment choices now available for advanced NSCLC, she feels like “a kid in the candy store.”
POSEIDON may give her “another choice,” but she pointed out that there are some aspects of the study to consider.
The study required patients to undergo four cycles of chemotherapy along with immunotherapy, “which certainly is standard in many of our practices.”
However, only two cycles of chemotherapy were given in the CheckMate 9LA trial, in which nivolumab (Opdivo) and ipilimumab (Yervoy) were added to chemotherapy for the treatment of stage IV NSCLC. This combination of immunotherapies, which block CTLA-4 and PD-1, is similar to the combination that was studied in the current trial, and it is already approved for use in some patients with lung cancer.
“Also key to point out,” said Dr. Brahmer, is that, in the POSEIDON trial, “there was a trend toward more poor prognostic factors in the chemotherapy arm, where these patients had more liver or central nervous system metastases.”
Despite these differences, the survival outcomes were similar in the two trials, and in both trials, the tails of the curves indicate that “we need to see long-term data” to determine whether the benefit is ongoing.
Which patients for which combos?
Considering all the data from key trials in advanced NSCLC, Dr. Brahmer said that she believes that, for patients with high PD-L1 expression, treatment with a single immunotherapy directed against PD-1 or PD-L1 “is appropriate” and that she didn’t see that adding a CTLA-4 inhibitor to the PD-L1 inhibitor and chemotherapy would give any advantage.
“But for PD-L1–negative disease, I do think CTLA-4 antibodies seem to provide a benefit, specifically seen in the CheckMate studies,” particularly for patients with squamous disease, although she noted that in POSEIDON, histology and PD-L1 status have not been analyzed.
Dr. Brahmer concluded that, although the triple therapy improved survival outcomes in the current study, several key questions remain.
These include determining what CTLA-4 inhibition adds to PD-L1 blockade and asking whether the “slightly increased toxicity” is “worth the slightly increased long-term duration of response” and improved survival outcomes.
Furthermore, it needs to be determined “which populations truly need” the combined approach; “to get to this, we need to find the biomarker for CTLA-4 benefit,” Dr. Brahmer said.
She also noted “a practical question: Is there room in the clinic for another CTLA-4 antibody in addition to the nivolumab/ipilimumab combinations?”
This last point was appreciated on social media. Jill Feldman, a lung cancer patient and advocate, described it on Twitter as a “great question.”
She said that, for her, “options equal hope,” but that it is “critical” to give the “best treatment first. ... So as a patient, I would ask: How do I know/you know which treatment would be best for me?”
With “so many options in the first-line setting,” subsets of patients who may benefit from quadruplet therapy versus monotherapy need to be defined, commented Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia. He added that “PD-L1 may be one biomarker, but we need more.”
More details of the POSEIDON trial
In the POSEIDON trial, investigators had the choice of different chemotherapy regimens: platinum/gemcitabine for patients with squamous disease, platinum/pemetrexed for patients with nonsquamous disease, and nab-paclitaxel/carboplatin for patients with disease of either histology, Dr. Johnson reported.
It is noteworthy that the majority of patients were from Eastern Europe and Asia, “and the proportion of squamous patients enrolled was higher than is typically seen in mixed histology lung cancer studies,” she added.
The patients were stratified by PD-L1 expression at a cutoff of 50%, disease stage, and tumor histology.
Overall, 1,013 patients were enrolled. The three treatment arms were relatively well balanced in terms of baseline characteristics.
Dr. Johnson noted that there were “a few minor imbalances” in the durvalumab plus tremelimumab arm, with “fewer females, fewer Asians, and fewer never-smokers relative to the other two arms.”
The primary endpoint analysis after a median follow-up of 10.3 months demonstrated that PFS was significantly improved with durvalumab plus chemotherapy over chemotherapy alone, at a median of 5.5 months versus 4.8 months (hazard ratio, 0.74; P = .00093).
Although OS improved numerically with the addition of durvalumab to chemotherapy, it did not reach significance (13.3 months vs. 11.7 months with chemotherapy alone; HR, 0.86; P = .07581).
The positive PFS benefit with durvalumab plus chemotherapy triggered a secondary endpoint analysis, which showed that adding tremelimumab to durvalumab plus chemotherapy improved both survival outcomes.
Median PFS with the triple combination therapy was 6.2 months, significantly longer than the 4.8 months seen with chemotherapy alone (HR, 0.72; P = .00031).
At 12 months, 26.6% of patients who underwent treatment with durvalumab plus tremelimumab plus chemotherapy had not experienced disease progression, compared with 13.1% in the chemotherapy-alone arm.
OS was also significantly improved, at 14.0 months among patients in the triple therapy arm versus 11.7 in the chemotherapy-alone arm (HR, 0.77; P = .00304).
The results also showed that at 24 months, 32.9% of triple therapy patients were still alive versus 22.1% in the chemotherapy-alone arm.
Analysis indicated that “most subgroups favored the addition of immunotherapy to chemotherapy.” There was a “trend toward improved survival for all patients treated with durvalumab plus tremelimumab plus chemotherapy,” Dr. Johnson said.
This was seen “in particular for the nonsquamous patients” and for those with tumor PD-L1 expression of less than 1%, he added.
It is notable that for a large proportion of combination-therapy patients, response had continued at 12 months. This was the case for 38.9% of those who underwent treatment with durvalumab plus chemotherapy and for 49.7% of those given triple therapy versus 21.4% in the chemotherapy-alone arm.
As was seen across the whole cohort, among patients with nonsquamous disease, PFS and OS improved with the addition of immunotherapy. Of those patients with nonsquamous disease, 95.5% received pemetrexed plus platinum chemotherapy.
However, among patients with squamous tumors, of whom 88.3% received gemcitabine plus platinum chemotherapy, PFS and OS were “poor ... across all treatment arms,” Dr. Johnson reported, “with little separation of the curves.”
She highlighted the fact that the proportion of patients who experienced grade 3/4 adverse events, whether of any cause or treatment related, was only slightly higher in the two immunotherapy arms, indicating that “most events were driven by the chemotherapy.”
The rates of treatment discontinuation and adverse events leading to death were also similar across the three treatment arms, albeit they were slightly higher with the addition of immunotherapy.
Dr. Johnson also noted that, although there were more immune-mediated adverse events with durvalumab plus tremelimumab plus chemotherapy, compared with durvalumab plus chemotherapy, the “majority were grade 1/2 and were manageable.”
The most common immune-mediated events in the two immunotherapy arms were hypothyroid and hepatic events, pneumonitis, dermatitis, and rash.
The study was sponsored by AstraZeneca. Dr. Johnson reported numerous relationships with pharmaceutical companies. Dr. Brahmer reported relationships with Amgen, AstratZeneca, BMA, Genentech/Roche, Eli Lilly, Eisai, GlaxoSmithKline, Janssen, Merck, RAPT Therapeutics, Regeneron, Revolution Medicine, and Sanofi.
A version of this article first appeared on Medscape.com.
The study involved over 1,000 patients with stage IV NSCLC. Participants were randomly assigned to receive either two ICIs (tremelimumab and durvalumab [Imfinzi]) plus chemotherapy, or one immunotherapy (durvalumab) plus chemotherapy, or chemotherapy alone.
Adding durvalumab to chemotherapy significantly improved PFS by 26% but did not significantly improve OS, the researchers reported. However, adding both tremelimumab and durvalumab significantly increased both PFS (by 28%) and OS (by 23%). Median OS was 14.0 months versus 11.7 months for chemotherapy.
The results were presented on Sept. 9 at a presidential symposium of the World Conference on Lung Cancer 2021.
The two immunotherapies act at different immune checkpoints – tremelimumab acts at CTLA-4, and durvalumab acts at programmed death–1/PD–ligand 1 (PD-L1). Both drugs are from AstraZeneca, which sponsored the POSEIDON trial.
With no new safety signals identified, the triple therapy combination “represents a potential new frontline treatment option for metastatic non–small cell lung cancer,” said lead researcher Melissa L. Johnson, MD, from the Sarah Cannon Research Institute, Nashville, Tenn.
Reacting to the new results in a discussion of the paper, Julie R. Brahmer, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, said that, with so many first-line treatment choices now available for advanced NSCLC, she feels like “a kid in the candy store.”
POSEIDON may give her “another choice,” but she pointed out that there are some aspects of the study to consider.
The study required patients to undergo four cycles of chemotherapy along with immunotherapy, “which certainly is standard in many of our practices.”
However, only two cycles of chemotherapy were given in the CheckMate 9LA trial, in which nivolumab (Opdivo) and ipilimumab (Yervoy) were added to chemotherapy for the treatment of stage IV NSCLC. This combination of immunotherapies, which block CTLA-4 and PD-1, is similar to the combination that was studied in the current trial, and it is already approved for use in some patients with lung cancer.
“Also key to point out,” said Dr. Brahmer, is that, in the POSEIDON trial, “there was a trend toward more poor prognostic factors in the chemotherapy arm, where these patients had more liver or central nervous system metastases.”
Despite these differences, the survival outcomes were similar in the two trials, and in both trials, the tails of the curves indicate that “we need to see long-term data” to determine whether the benefit is ongoing.
Which patients for which combos?
Considering all the data from key trials in advanced NSCLC, Dr. Brahmer said that she believes that, for patients with high PD-L1 expression, treatment with a single immunotherapy directed against PD-1 or PD-L1 “is appropriate” and that she didn’t see that adding a CTLA-4 inhibitor to the PD-L1 inhibitor and chemotherapy would give any advantage.
“But for PD-L1–negative disease, I do think CTLA-4 antibodies seem to provide a benefit, specifically seen in the CheckMate studies,” particularly for patients with squamous disease, although she noted that in POSEIDON, histology and PD-L1 status have not been analyzed.
Dr. Brahmer concluded that, although the triple therapy improved survival outcomes in the current study, several key questions remain.
These include determining what CTLA-4 inhibition adds to PD-L1 blockade and asking whether the “slightly increased toxicity” is “worth the slightly increased long-term duration of response” and improved survival outcomes.
Furthermore, it needs to be determined “which populations truly need” the combined approach; “to get to this, we need to find the biomarker for CTLA-4 benefit,” Dr. Brahmer said.
She also noted “a practical question: Is there room in the clinic for another CTLA-4 antibody in addition to the nivolumab/ipilimumab combinations?”
This last point was appreciated on social media. Jill Feldman, a lung cancer patient and advocate, described it on Twitter as a “great question.”
She said that, for her, “options equal hope,” but that it is “critical” to give the “best treatment first. ... So as a patient, I would ask: How do I know/you know which treatment would be best for me?”
With “so many options in the first-line setting,” subsets of patients who may benefit from quadruplet therapy versus monotherapy need to be defined, commented Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia. He added that “PD-L1 may be one biomarker, but we need more.”
More details of the POSEIDON trial
In the POSEIDON trial, investigators had the choice of different chemotherapy regimens: platinum/gemcitabine for patients with squamous disease, platinum/pemetrexed for patients with nonsquamous disease, and nab-paclitaxel/carboplatin for patients with disease of either histology, Dr. Johnson reported.
It is noteworthy that the majority of patients were from Eastern Europe and Asia, “and the proportion of squamous patients enrolled was higher than is typically seen in mixed histology lung cancer studies,” she added.
The patients were stratified by PD-L1 expression at a cutoff of 50%, disease stage, and tumor histology.
Overall, 1,013 patients were enrolled. The three treatment arms were relatively well balanced in terms of baseline characteristics.
Dr. Johnson noted that there were “a few minor imbalances” in the durvalumab plus tremelimumab arm, with “fewer females, fewer Asians, and fewer never-smokers relative to the other two arms.”
The primary endpoint analysis after a median follow-up of 10.3 months demonstrated that PFS was significantly improved with durvalumab plus chemotherapy over chemotherapy alone, at a median of 5.5 months versus 4.8 months (hazard ratio, 0.74; P = .00093).
Although OS improved numerically with the addition of durvalumab to chemotherapy, it did not reach significance (13.3 months vs. 11.7 months with chemotherapy alone; HR, 0.86; P = .07581).
The positive PFS benefit with durvalumab plus chemotherapy triggered a secondary endpoint analysis, which showed that adding tremelimumab to durvalumab plus chemotherapy improved both survival outcomes.
Median PFS with the triple combination therapy was 6.2 months, significantly longer than the 4.8 months seen with chemotherapy alone (HR, 0.72; P = .00031).
At 12 months, 26.6% of patients who underwent treatment with durvalumab plus tremelimumab plus chemotherapy had not experienced disease progression, compared with 13.1% in the chemotherapy-alone arm.
OS was also significantly improved, at 14.0 months among patients in the triple therapy arm versus 11.7 in the chemotherapy-alone arm (HR, 0.77; P = .00304).
The results also showed that at 24 months, 32.9% of triple therapy patients were still alive versus 22.1% in the chemotherapy-alone arm.
Analysis indicated that “most subgroups favored the addition of immunotherapy to chemotherapy.” There was a “trend toward improved survival for all patients treated with durvalumab plus tremelimumab plus chemotherapy,” Dr. Johnson said.
This was seen “in particular for the nonsquamous patients” and for those with tumor PD-L1 expression of less than 1%, he added.
It is notable that for a large proportion of combination-therapy patients, response had continued at 12 months. This was the case for 38.9% of those who underwent treatment with durvalumab plus chemotherapy and for 49.7% of those given triple therapy versus 21.4% in the chemotherapy-alone arm.
As was seen across the whole cohort, among patients with nonsquamous disease, PFS and OS improved with the addition of immunotherapy. Of those patients with nonsquamous disease, 95.5% received pemetrexed plus platinum chemotherapy.
However, among patients with squamous tumors, of whom 88.3% received gemcitabine plus platinum chemotherapy, PFS and OS were “poor ... across all treatment arms,” Dr. Johnson reported, “with little separation of the curves.”
She highlighted the fact that the proportion of patients who experienced grade 3/4 adverse events, whether of any cause or treatment related, was only slightly higher in the two immunotherapy arms, indicating that “most events were driven by the chemotherapy.”
The rates of treatment discontinuation and adverse events leading to death were also similar across the three treatment arms, albeit they were slightly higher with the addition of immunotherapy.
Dr. Johnson also noted that, although there were more immune-mediated adverse events with durvalumab plus tremelimumab plus chemotherapy, compared with durvalumab plus chemotherapy, the “majority were grade 1/2 and were manageable.”
The most common immune-mediated events in the two immunotherapy arms were hypothyroid and hepatic events, pneumonitis, dermatitis, and rash.
The study was sponsored by AstraZeneca. Dr. Johnson reported numerous relationships with pharmaceutical companies. Dr. Brahmer reported relationships with Amgen, AstratZeneca, BMA, Genentech/Roche, Eli Lilly, Eisai, GlaxoSmithKline, Janssen, Merck, RAPT Therapeutics, Regeneron, Revolution Medicine, and Sanofi.
A version of this article first appeared on Medscape.com.
The study involved over 1,000 patients with stage IV NSCLC. Participants were randomly assigned to receive either two ICIs (tremelimumab and durvalumab [Imfinzi]) plus chemotherapy, or one immunotherapy (durvalumab) plus chemotherapy, or chemotherapy alone.
Adding durvalumab to chemotherapy significantly improved PFS by 26% but did not significantly improve OS, the researchers reported. However, adding both tremelimumab and durvalumab significantly increased both PFS (by 28%) and OS (by 23%). Median OS was 14.0 months versus 11.7 months for chemotherapy.
The results were presented on Sept. 9 at a presidential symposium of the World Conference on Lung Cancer 2021.
The two immunotherapies act at different immune checkpoints – tremelimumab acts at CTLA-4, and durvalumab acts at programmed death–1/PD–ligand 1 (PD-L1). Both drugs are from AstraZeneca, which sponsored the POSEIDON trial.
With no new safety signals identified, the triple therapy combination “represents a potential new frontline treatment option for metastatic non–small cell lung cancer,” said lead researcher Melissa L. Johnson, MD, from the Sarah Cannon Research Institute, Nashville, Tenn.
Reacting to the new results in a discussion of the paper, Julie R. Brahmer, MD, from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, said that, with so many first-line treatment choices now available for advanced NSCLC, she feels like “a kid in the candy store.”
POSEIDON may give her “another choice,” but she pointed out that there are some aspects of the study to consider.
The study required patients to undergo four cycles of chemotherapy along with immunotherapy, “which certainly is standard in many of our practices.”
However, only two cycles of chemotherapy were given in the CheckMate 9LA trial, in which nivolumab (Opdivo) and ipilimumab (Yervoy) were added to chemotherapy for the treatment of stage IV NSCLC. This combination of immunotherapies, which block CTLA-4 and PD-1, is similar to the combination that was studied in the current trial, and it is already approved for use in some patients with lung cancer.
“Also key to point out,” said Dr. Brahmer, is that, in the POSEIDON trial, “there was a trend toward more poor prognostic factors in the chemotherapy arm, where these patients had more liver or central nervous system metastases.”
Despite these differences, the survival outcomes were similar in the two trials, and in both trials, the tails of the curves indicate that “we need to see long-term data” to determine whether the benefit is ongoing.
Which patients for which combos?
Considering all the data from key trials in advanced NSCLC, Dr. Brahmer said that she believes that, for patients with high PD-L1 expression, treatment with a single immunotherapy directed against PD-1 or PD-L1 “is appropriate” and that she didn’t see that adding a CTLA-4 inhibitor to the PD-L1 inhibitor and chemotherapy would give any advantage.
“But for PD-L1–negative disease, I do think CTLA-4 antibodies seem to provide a benefit, specifically seen in the CheckMate studies,” particularly for patients with squamous disease, although she noted that in POSEIDON, histology and PD-L1 status have not been analyzed.
Dr. Brahmer concluded that, although the triple therapy improved survival outcomes in the current study, several key questions remain.
These include determining what CTLA-4 inhibition adds to PD-L1 blockade and asking whether the “slightly increased toxicity” is “worth the slightly increased long-term duration of response” and improved survival outcomes.
Furthermore, it needs to be determined “which populations truly need” the combined approach; “to get to this, we need to find the biomarker for CTLA-4 benefit,” Dr. Brahmer said.
She also noted “a practical question: Is there room in the clinic for another CTLA-4 antibody in addition to the nivolumab/ipilimumab combinations?”
This last point was appreciated on social media. Jill Feldman, a lung cancer patient and advocate, described it on Twitter as a “great question.”
She said that, for her, “options equal hope,” but that it is “critical” to give the “best treatment first. ... So as a patient, I would ask: How do I know/you know which treatment would be best for me?”
With “so many options in the first-line setting,” subsets of patients who may benefit from quadruplet therapy versus monotherapy need to be defined, commented Charu Aggarwal, MD, MPH, Leslye M. Heisler Associate Professor for Lung Cancer Excellence, Penn Medicine, Philadelphia. He added that “PD-L1 may be one biomarker, but we need more.”
More details of the POSEIDON trial
In the POSEIDON trial, investigators had the choice of different chemotherapy regimens: platinum/gemcitabine for patients with squamous disease, platinum/pemetrexed for patients with nonsquamous disease, and nab-paclitaxel/carboplatin for patients with disease of either histology, Dr. Johnson reported.
It is noteworthy that the majority of patients were from Eastern Europe and Asia, “and the proportion of squamous patients enrolled was higher than is typically seen in mixed histology lung cancer studies,” she added.
The patients were stratified by PD-L1 expression at a cutoff of 50%, disease stage, and tumor histology.
Overall, 1,013 patients were enrolled. The three treatment arms were relatively well balanced in terms of baseline characteristics.
Dr. Johnson noted that there were “a few minor imbalances” in the durvalumab plus tremelimumab arm, with “fewer females, fewer Asians, and fewer never-smokers relative to the other two arms.”
The primary endpoint analysis after a median follow-up of 10.3 months demonstrated that PFS was significantly improved with durvalumab plus chemotherapy over chemotherapy alone, at a median of 5.5 months versus 4.8 months (hazard ratio, 0.74; P = .00093).
Although OS improved numerically with the addition of durvalumab to chemotherapy, it did not reach significance (13.3 months vs. 11.7 months with chemotherapy alone; HR, 0.86; P = .07581).
The positive PFS benefit with durvalumab plus chemotherapy triggered a secondary endpoint analysis, which showed that adding tremelimumab to durvalumab plus chemotherapy improved both survival outcomes.
Median PFS with the triple combination therapy was 6.2 months, significantly longer than the 4.8 months seen with chemotherapy alone (HR, 0.72; P = .00031).
At 12 months, 26.6% of patients who underwent treatment with durvalumab plus tremelimumab plus chemotherapy had not experienced disease progression, compared with 13.1% in the chemotherapy-alone arm.
OS was also significantly improved, at 14.0 months among patients in the triple therapy arm versus 11.7 in the chemotherapy-alone arm (HR, 0.77; P = .00304).
The results also showed that at 24 months, 32.9% of triple therapy patients were still alive versus 22.1% in the chemotherapy-alone arm.
Analysis indicated that “most subgroups favored the addition of immunotherapy to chemotherapy.” There was a “trend toward improved survival for all patients treated with durvalumab plus tremelimumab plus chemotherapy,” Dr. Johnson said.
This was seen “in particular for the nonsquamous patients” and for those with tumor PD-L1 expression of less than 1%, he added.
It is notable that for a large proportion of combination-therapy patients, response had continued at 12 months. This was the case for 38.9% of those who underwent treatment with durvalumab plus chemotherapy and for 49.7% of those given triple therapy versus 21.4% in the chemotherapy-alone arm.
As was seen across the whole cohort, among patients with nonsquamous disease, PFS and OS improved with the addition of immunotherapy. Of those patients with nonsquamous disease, 95.5% received pemetrexed plus platinum chemotherapy.
However, among patients with squamous tumors, of whom 88.3% received gemcitabine plus platinum chemotherapy, PFS and OS were “poor ... across all treatment arms,” Dr. Johnson reported, “with little separation of the curves.”
She highlighted the fact that the proportion of patients who experienced grade 3/4 adverse events, whether of any cause or treatment related, was only slightly higher in the two immunotherapy arms, indicating that “most events were driven by the chemotherapy.”
The rates of treatment discontinuation and adverse events leading to death were also similar across the three treatment arms, albeit they were slightly higher with the addition of immunotherapy.
Dr. Johnson also noted that, although there were more immune-mediated adverse events with durvalumab plus tremelimumab plus chemotherapy, compared with durvalumab plus chemotherapy, the “majority were grade 1/2 and were manageable.”
The most common immune-mediated events in the two immunotherapy arms were hypothyroid and hepatic events, pneumonitis, dermatitis, and rash.
The study was sponsored by AstraZeneca. Dr. Johnson reported numerous relationships with pharmaceutical companies. Dr. Brahmer reported relationships with Amgen, AstratZeneca, BMA, Genentech/Roche, Eli Lilly, Eisai, GlaxoSmithKline, Janssen, Merck, RAPT Therapeutics, Regeneron, Revolution Medicine, and Sanofi.
A version of this article first appeared on Medscape.com.
Combo treatment for NSCLC with brain metastases extends survival by two years for some
The trial is noteworthy because to date, few patients with nonsquamous NSCLC and untreated asymptomatic brain metastases (or those treated with corticosteroids), were ever included in clinical trials that examine the efficacy and safety of chemotherapy and immunotherapy together as first-line treatment, said Ernest Nadal, MD, PhD, of the University of Barcelona Catalan Institute of Oncology at L’Hospitalet de Llobregat. He and his colleagues presented their findings at the meeting, which was organized by the International Association for the Study of Lung Cancer (IASLC).
With only 40 patients, the clinical trial was small, but the safety profile of atezolizumab combined with carboplatin and pemetrexed was favorable in patients with untreated brain metastases and those receiving corticosteroids (dexamethasone of 4 mg once a day or less).
At a median follow-up of 17.3 months, median intracranial and systemic progression-free survival – the co-primary study endpoints, along with safety – were 6.9 months and 8.9 months in 40 patients treated with the immune checkpoint inhibitor and chemotherapy combination, and the 18-month progression-free survival rates were 10.4% and 24.9%, respectively, Dr. Nadal said.
Secondary study endpoints included response rate and overall survival rate. The overall response rate was 40% at 12 weeks; 19 patients (47.5%) had stable disease in the central nervous system, and 19 (47.5%) had a systemic response. The median overall survival was 13.6 months, and 2-year overall survival was 32%.
“The 12-week progression-free survival rate was 60%, [which was] above the expected rate of 50%, and the grade 2-4 toxicity rate was 27.5%, [which was] below the threshold of 35%,” Dr. Nadal said.
Four patients achieved complete response in the brain, and four patients had discordance between systemic and central nervous system response: two with progressive disease in the body and stable disease in the brain, and two with progressive disease in the brain and stable disease in the body.
Study subjects were chemotherapy-naive patients with stage IV non-squamous NSCLC without estimated glomerular filtration rate (EGFR) or anaplastic lymphoma kinase (ALK) genetic alterations and with untreated brain metastases. They were enrolled from 11 clinical sites and treated with carboplatin (5 AUCs) and pemetrexed (500 mg/m2) plus atezolizumab (1,200 mg) every 3 weeks for four to six cycles, followed by maintenance with pemetrexed plus atezolizumab for 2 years or until disease progression or unacceptable toxicity.
Grade 3 treatment-related adverse events occurring in at least 5% of patients were anemia (eight patients), back pain (four patients), thrombocytopenia (two patients) and dyspnea, pneumonitis, and elevated alanine transaminase (one patient each). Grade 4 treatment-related adverse events occurred in three patients and included thrombocytopenia, neutropenia, and hallucinations.
“Brain metastases are the most frequent cancer-related neurological complication and have a major impact on the neurocognitive function, quality of life, and the patient’s prognosis,” Dr. Nadal said, adding that local therapy could add toxicity and delay systemic treatment.
The progression-free survival findings in this study are similar to those reported in the KEYNOTE-189 clinical trial in patients with brain metastases, which showed improved outcomes with pembrolizumab plus chemotherapy in patients with previously untreated metastatic nonsquamous NSCLC, Dr. Nadal said.
The safety profile was also favorable – even in the 17 patients receiving corticosteroids at baseline.
“This combination can result in clinical benefit in terms of overall survival in this population “Correlative studies with brain imaging and blood samples are currently ongoing,” he said.
Charu Aggarwal, MD, MPH, an oncologist with Penn Medicine who specializes in lung cancer, said the findings help address how patients with untreated, asymptomatic brain metastases should be treated.
Taken together with findings from other prospective and retrospective trials in this population, the outcomes demonstrate that “in patients with asymptomatic brain metastases, upfront immunochemotherapy is associated with intracranial response rates,” she said. Patients with asymptomatic brain metastases can be safely treated with chemoimmunotherapy, but “proper patient selection is going to be key.”
Unanswered questions from this study include the size of brain metastases at trial enrollment, whether programmed death-ligand 1 status matters, and whether there is an optimal dose of steroids that should be mandated for inclusion into trials, Dr. Aggarwal added, noting that several trials enrolling patients with lung cancer are seeking to answer these questions.
Dr. Nadal reported receiving research support, speaker bureau fees, and/or honoraria from multiple pharmaceutical companies. Dr. Aggarwal reported serving on an advisory board for multiple pharmaceutical companies. She also reported clinical trial funding to her institution from multiple companies.
The trial is noteworthy because to date, few patients with nonsquamous NSCLC and untreated asymptomatic brain metastases (or those treated with corticosteroids), were ever included in clinical trials that examine the efficacy and safety of chemotherapy and immunotherapy together as first-line treatment, said Ernest Nadal, MD, PhD, of the University of Barcelona Catalan Institute of Oncology at L’Hospitalet de Llobregat. He and his colleagues presented their findings at the meeting, which was organized by the International Association for the Study of Lung Cancer (IASLC).
With only 40 patients, the clinical trial was small, but the safety profile of atezolizumab combined with carboplatin and pemetrexed was favorable in patients with untreated brain metastases and those receiving corticosteroids (dexamethasone of 4 mg once a day or less).
At a median follow-up of 17.3 months, median intracranial and systemic progression-free survival – the co-primary study endpoints, along with safety – were 6.9 months and 8.9 months in 40 patients treated with the immune checkpoint inhibitor and chemotherapy combination, and the 18-month progression-free survival rates were 10.4% and 24.9%, respectively, Dr. Nadal said.
Secondary study endpoints included response rate and overall survival rate. The overall response rate was 40% at 12 weeks; 19 patients (47.5%) had stable disease in the central nervous system, and 19 (47.5%) had a systemic response. The median overall survival was 13.6 months, and 2-year overall survival was 32%.
“The 12-week progression-free survival rate was 60%, [which was] above the expected rate of 50%, and the grade 2-4 toxicity rate was 27.5%, [which was] below the threshold of 35%,” Dr. Nadal said.
Four patients achieved complete response in the brain, and four patients had discordance between systemic and central nervous system response: two with progressive disease in the body and stable disease in the brain, and two with progressive disease in the brain and stable disease in the body.
Study subjects were chemotherapy-naive patients with stage IV non-squamous NSCLC without estimated glomerular filtration rate (EGFR) or anaplastic lymphoma kinase (ALK) genetic alterations and with untreated brain metastases. They were enrolled from 11 clinical sites and treated with carboplatin (5 AUCs) and pemetrexed (500 mg/m2) plus atezolizumab (1,200 mg) every 3 weeks for four to six cycles, followed by maintenance with pemetrexed plus atezolizumab for 2 years or until disease progression or unacceptable toxicity.
Grade 3 treatment-related adverse events occurring in at least 5% of patients were anemia (eight patients), back pain (four patients), thrombocytopenia (two patients) and dyspnea, pneumonitis, and elevated alanine transaminase (one patient each). Grade 4 treatment-related adverse events occurred in three patients and included thrombocytopenia, neutropenia, and hallucinations.
“Brain metastases are the most frequent cancer-related neurological complication and have a major impact on the neurocognitive function, quality of life, and the patient’s prognosis,” Dr. Nadal said, adding that local therapy could add toxicity and delay systemic treatment.
The progression-free survival findings in this study are similar to those reported in the KEYNOTE-189 clinical trial in patients with brain metastases, which showed improved outcomes with pembrolizumab plus chemotherapy in patients with previously untreated metastatic nonsquamous NSCLC, Dr. Nadal said.
The safety profile was also favorable – even in the 17 patients receiving corticosteroids at baseline.
“This combination can result in clinical benefit in terms of overall survival in this population “Correlative studies with brain imaging and blood samples are currently ongoing,” he said.
Charu Aggarwal, MD, MPH, an oncologist with Penn Medicine who specializes in lung cancer, said the findings help address how patients with untreated, asymptomatic brain metastases should be treated.
Taken together with findings from other prospective and retrospective trials in this population, the outcomes demonstrate that “in patients with asymptomatic brain metastases, upfront immunochemotherapy is associated with intracranial response rates,” she said. Patients with asymptomatic brain metastases can be safely treated with chemoimmunotherapy, but “proper patient selection is going to be key.”
Unanswered questions from this study include the size of brain metastases at trial enrollment, whether programmed death-ligand 1 status matters, and whether there is an optimal dose of steroids that should be mandated for inclusion into trials, Dr. Aggarwal added, noting that several trials enrolling patients with lung cancer are seeking to answer these questions.
Dr. Nadal reported receiving research support, speaker bureau fees, and/or honoraria from multiple pharmaceutical companies. Dr. Aggarwal reported serving on an advisory board for multiple pharmaceutical companies. She also reported clinical trial funding to her institution from multiple companies.
The trial is noteworthy because to date, few patients with nonsquamous NSCLC and untreated asymptomatic brain metastases (or those treated with corticosteroids), were ever included in clinical trials that examine the efficacy and safety of chemotherapy and immunotherapy together as first-line treatment, said Ernest Nadal, MD, PhD, of the University of Barcelona Catalan Institute of Oncology at L’Hospitalet de Llobregat. He and his colleagues presented their findings at the meeting, which was organized by the International Association for the Study of Lung Cancer (IASLC).
With only 40 patients, the clinical trial was small, but the safety profile of atezolizumab combined with carboplatin and pemetrexed was favorable in patients with untreated brain metastases and those receiving corticosteroids (dexamethasone of 4 mg once a day or less).
At a median follow-up of 17.3 months, median intracranial and systemic progression-free survival – the co-primary study endpoints, along with safety – were 6.9 months and 8.9 months in 40 patients treated with the immune checkpoint inhibitor and chemotherapy combination, and the 18-month progression-free survival rates were 10.4% and 24.9%, respectively, Dr. Nadal said.
Secondary study endpoints included response rate and overall survival rate. The overall response rate was 40% at 12 weeks; 19 patients (47.5%) had stable disease in the central nervous system, and 19 (47.5%) had a systemic response. The median overall survival was 13.6 months, and 2-year overall survival was 32%.
“The 12-week progression-free survival rate was 60%, [which was] above the expected rate of 50%, and the grade 2-4 toxicity rate was 27.5%, [which was] below the threshold of 35%,” Dr. Nadal said.
Four patients achieved complete response in the brain, and four patients had discordance between systemic and central nervous system response: two with progressive disease in the body and stable disease in the brain, and two with progressive disease in the brain and stable disease in the body.
Study subjects were chemotherapy-naive patients with stage IV non-squamous NSCLC without estimated glomerular filtration rate (EGFR) or anaplastic lymphoma kinase (ALK) genetic alterations and with untreated brain metastases. They were enrolled from 11 clinical sites and treated with carboplatin (5 AUCs) and pemetrexed (500 mg/m2) plus atezolizumab (1,200 mg) every 3 weeks for four to six cycles, followed by maintenance with pemetrexed plus atezolizumab for 2 years or until disease progression or unacceptable toxicity.
Grade 3 treatment-related adverse events occurring in at least 5% of patients were anemia (eight patients), back pain (four patients), thrombocytopenia (two patients) and dyspnea, pneumonitis, and elevated alanine transaminase (one patient each). Grade 4 treatment-related adverse events occurred in three patients and included thrombocytopenia, neutropenia, and hallucinations.
“Brain metastases are the most frequent cancer-related neurological complication and have a major impact on the neurocognitive function, quality of life, and the patient’s prognosis,” Dr. Nadal said, adding that local therapy could add toxicity and delay systemic treatment.
The progression-free survival findings in this study are similar to those reported in the KEYNOTE-189 clinical trial in patients with brain metastases, which showed improved outcomes with pembrolizumab plus chemotherapy in patients with previously untreated metastatic nonsquamous NSCLC, Dr. Nadal said.
The safety profile was also favorable – even in the 17 patients receiving corticosteroids at baseline.
“This combination can result in clinical benefit in terms of overall survival in this population “Correlative studies with brain imaging and blood samples are currently ongoing,” he said.
Charu Aggarwal, MD, MPH, an oncologist with Penn Medicine who specializes in lung cancer, said the findings help address how patients with untreated, asymptomatic brain metastases should be treated.
Taken together with findings from other prospective and retrospective trials in this population, the outcomes demonstrate that “in patients with asymptomatic brain metastases, upfront immunochemotherapy is associated with intracranial response rates,” she said. Patients with asymptomatic brain metastases can be safely treated with chemoimmunotherapy, but “proper patient selection is going to be key.”
Unanswered questions from this study include the size of brain metastases at trial enrollment, whether programmed death-ligand 1 status matters, and whether there is an optimal dose of steroids that should be mandated for inclusion into trials, Dr. Aggarwal added, noting that several trials enrolling patients with lung cancer are seeking to answer these questions.
Dr. Nadal reported receiving research support, speaker bureau fees, and/or honoraria from multiple pharmaceutical companies. Dr. Aggarwal reported serving on an advisory board for multiple pharmaceutical companies. She also reported clinical trial funding to her institution from multiple companies.
REPORTING FROM WCLC 2021
COVID is especially dangerous for mesothelioma
according to Susana Cedres, MD, PhD, a thoracic medical oncologist at Vall d’Hebron University Hospital, Barcelona.
At the annual World Conference on Lung Cancer, she reported on her institution’s experience during the first year of the pandemic before widespread vaccine rollouts.
Among 38 malignant pleural mesothelioma (MPM) patients, seven (18%) patients were diagnosed with COVID-19 and of these, three patients were asymptomatic, four (57%) died of complications including bilateral pneumonia within a median of less than half a month after diagnosis, and a fifth patient died from MPM progression.
The findings confirm the particular risk of COVID in MPM. According to researchers reporting in Scientific Reports, mesothelioma was the only cancer linked to significantly worse outcomes. Other risks included tuberculosis, drug use, hepatitis, HIV/AIDS, cardiomyopathy, and diabetes.
However, the Barcelona report only has seven patients, and it’s one of only a few to address the specifics of COVID in MPM.
“There really is a need for more inclusion of MPM patients in international [COVID] registries” to better characterize the course of infection and improve outcomes, said study discussant Francoise Galateau-Salle, MD, PhD, a mesothelioma expert at the Cancer Center Leon Berard in Lyon, France.
Among the seven positive cases in Barcelona, almost all had comorbidities, with the most common being cardiovascular disease in four patients (57%). Only two patients (29%) were on oncologic treatment at the time they were diagnosed, and the median age at diagnosis was 62 years. Four cases were in men, three in women. MPM stage was not reported.
WCLC 2021 was organized by the International Association for the Study of Lung Cancer.
No funding source was reported. Dr. Cedres is an adviser and/or reported travel expenses from a number of companies, including Merck, Pfizer, and Bristol-Myers Squibb. Dr. Galateau-Salle had no disclosures.
according to Susana Cedres, MD, PhD, a thoracic medical oncologist at Vall d’Hebron University Hospital, Barcelona.
At the annual World Conference on Lung Cancer, she reported on her institution’s experience during the first year of the pandemic before widespread vaccine rollouts.
Among 38 malignant pleural mesothelioma (MPM) patients, seven (18%) patients were diagnosed with COVID-19 and of these, three patients were asymptomatic, four (57%) died of complications including bilateral pneumonia within a median of less than half a month after diagnosis, and a fifth patient died from MPM progression.
The findings confirm the particular risk of COVID in MPM. According to researchers reporting in Scientific Reports, mesothelioma was the only cancer linked to significantly worse outcomes. Other risks included tuberculosis, drug use, hepatitis, HIV/AIDS, cardiomyopathy, and diabetes.
However, the Barcelona report only has seven patients, and it’s one of only a few to address the specifics of COVID in MPM.
“There really is a need for more inclusion of MPM patients in international [COVID] registries” to better characterize the course of infection and improve outcomes, said study discussant Francoise Galateau-Salle, MD, PhD, a mesothelioma expert at the Cancer Center Leon Berard in Lyon, France.
Among the seven positive cases in Barcelona, almost all had comorbidities, with the most common being cardiovascular disease in four patients (57%). Only two patients (29%) were on oncologic treatment at the time they were diagnosed, and the median age at diagnosis was 62 years. Four cases were in men, three in women. MPM stage was not reported.
WCLC 2021 was organized by the International Association for the Study of Lung Cancer.
No funding source was reported. Dr. Cedres is an adviser and/or reported travel expenses from a number of companies, including Merck, Pfizer, and Bristol-Myers Squibb. Dr. Galateau-Salle had no disclosures.
according to Susana Cedres, MD, PhD, a thoracic medical oncologist at Vall d’Hebron University Hospital, Barcelona.
At the annual World Conference on Lung Cancer, she reported on her institution’s experience during the first year of the pandemic before widespread vaccine rollouts.
Among 38 malignant pleural mesothelioma (MPM) patients, seven (18%) patients were diagnosed with COVID-19 and of these, three patients were asymptomatic, four (57%) died of complications including bilateral pneumonia within a median of less than half a month after diagnosis, and a fifth patient died from MPM progression.
The findings confirm the particular risk of COVID in MPM. According to researchers reporting in Scientific Reports, mesothelioma was the only cancer linked to significantly worse outcomes. Other risks included tuberculosis, drug use, hepatitis, HIV/AIDS, cardiomyopathy, and diabetes.
However, the Barcelona report only has seven patients, and it’s one of only a few to address the specifics of COVID in MPM.
“There really is a need for more inclusion of MPM patients in international [COVID] registries” to better characterize the course of infection and improve outcomes, said study discussant Francoise Galateau-Salle, MD, PhD, a mesothelioma expert at the Cancer Center Leon Berard in Lyon, France.
Among the seven positive cases in Barcelona, almost all had comorbidities, with the most common being cardiovascular disease in four patients (57%). Only two patients (29%) were on oncologic treatment at the time they were diagnosed, and the median age at diagnosis was 62 years. Four cases were in men, three in women. MPM stage was not reported.
WCLC 2021 was organized by the International Association for the Study of Lung Cancer.
No funding source was reported. Dr. Cedres is an adviser and/or reported travel expenses from a number of companies, including Merck, Pfizer, and Bristol-Myers Squibb. Dr. Galateau-Salle had no disclosures.
FROM WCLC 2021
Pandemic strategies to boost trial enrollment should stay
Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.
These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.
These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).
Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.
Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.
Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.
These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.
“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.
The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.
Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.
This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.
Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.
Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.
The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.
“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.
However, she expressed concern that “with the telehealth visits, we can create some disparities.”
“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.
Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”
Impact on lung cancer clinical trials
The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.
Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.
The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).
The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.
The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).
Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).
Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).
“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.
Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.
This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).
Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).
The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.
Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.
The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.
A version of this article first appeared on Medscape.com.
Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.
These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.
These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).
Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.
Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.
Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.
These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.
“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.
The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.
Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.
This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.
Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.
Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.
The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.
“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.
However, she expressed concern that “with the telehealth visits, we can create some disparities.”
“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.
Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”
Impact on lung cancer clinical trials
The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.
Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.
The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).
The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.
The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).
Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).
Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).
“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.
Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.
This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).
Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).
The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.
Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.
The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.
A version of this article first appeared on Medscape.com.
Although enrollment into lung cancer clinical trials fell during the early months of the COVID-19 pandemic, it increased after a number of mitigation strategies were introduced.
These strategies should now be maintained, say experts, in order to improve enrollment and access to trials and to ensure that trials are more pragmatic and streamlined.
These were the findings from a survey sent to 173 sites of clinical trials in 45 countries around the world. The findings were presented recently at the World Conference on Lung Cancer (WCLC) 2021. The meeting and the survey were organized by the International Association for the Study of Lung Cancer (IASLC).
Responses to the survey revealed that enrollment into lung cancer trials fell by 43% during the early months of the pandemic. Patients stopped attending clinics, and some trials were suspended.
Patients were less willing to visit clinical trial sites, and lockdown restrictions made travel difficult.
Organizers of clinical trials responded by implementing mitigation strategies, such as changing monitoring requirements, increasing use of telehealth, and using local non-study facilities for laboratory and radiology services.
These measures led to an increase in trial enrollment toward the end of 2020, the survey results show.
“The COVID-19 pandemic created many challenges [that led to] reductions in lung cancer clinical trial enrollment,” commented study presenter Matthew P. Smeltzer, PhD, from the Division of Epidemiology, Biostatistics, and Environmental Health, University of Memphis.
The employment of mitigation strategies allowed the removal of “barriers,” and although the pandemic “worsened, trial enrollment began to improve due in part to these strategies,” Dr. Smeltzer said.
Many of these measures were successful and should be maintained, he suggested. Strategies include allowing telehealth visits, performing testing at local laboratories, using local radiology services, mailing experimental agents “where possible,” and allowing flexibility in trial schedules.
This is a “very important” study, commented Marina Garassino, MD, professor of medicine, hematology, and oncology, the University of Chicago Medicine, in her discussion of the abstract.
Irrespective of the pandemic, the regulation and the bureaucracy of clinical trials hinder participation by patients and physicians, she said.
Many of the mitigation strategies highlighted by the survey were similar to recommendations on the conduct of clinical trials published by the American Society of Clinical Oncology during the pandemic. Those recommendations emphasize the use of telehealth and offsite strategies to help with patient monitoring, she noted.
The findings from the survey show that it is possible to conduct more “streamlined and pragmatic trials,” she said.
“More flexible approaches should be approved by the sponsors of clinical trials and global regulatory bodies,” she added.
However, she expressed concern that “with the telehealth visits, we can create some disparities.”
“We have to remember that lung cancer patients are sometimes a very old population, and they are not digitally evolved,” she commented.
Commenting on Twitter, Jennifer C. King, PhD, chief scientific officer at the GO2 Foundation for Lung Cancer, in Washington, D.C., agreed that many of the mitigation strategies identified in the study “are good for patients all of the time, not just during a pandemic.”
Impact on lung cancer clinical trials
The survey, which included 64 questions, was intended to assess the impact of the COVID pandemic on lung cancer clinical trials.
Most of the survey responses came from sites in Europe (37.6%); 21.4% came from Asia, 13.3% came from the United States, and 7.5% came from Canada.
The team found that enrollment into lung cancer trials declined by 43% in 2020 compared to 2019, at an incidence rate ratio of 0.57 (P = .0115).
The largest decreases in enrollment were between April and August 2020, Dr. Smeltzer noted. However, in the last quarter of 2020 (October to December), the differences in enrollment were significantly smaller (P = .0160), despite a marked increase in global COVID-19 cases per month, he added.
The most common challenges faced by clinical trial sites during the pandemic were the following: There were fewer eligible patients (cited by 67% of respondents); compliance protocol was worse (61%); trials were suspended (60%); there was a lack of research staff (48%); and there were institutional closures (39%).
Regarding patient-related challenges, 67% of sites cited less willingness to visit the site. Other challenges included less ability to travel (cited by 60%), reduced access to the trial site (52%), quarantining because of exposure to COVID-19 (40%), and SARS-CoV-2 infection (26%).
Concerns of patients included the following: Fear of SARS-CoV-2 infection, which was cited by 83%; travel restrictions (47%); securing transportation (38%); and access to the laboratory/radiology services (14%).
“Patient willingness to visit the site was a consistent barrier reported across Europe, the U.S., and Canada,” said Dr. Smeltzer, although the effect was smaller in North America, he added.
Regarding mitigation strategies that were employed during the pandemic to combat the challenges and concerns, the team found that the most common measure was the modification of monitoring requirements, used by 44% of sites.
This was followed by the use of telehealth visits (43% sites), the use of laboratories at non-study facilities ( 27%), and alterations to the number of required visits (25%).
Other mitigation strategies included use of mail-order medications, (24%), using radiology services at a non-study site (20%), and altering the trial schedules (19%).
The most effective mitigation strategies were felt to be those that allowed flexibility with respect to location. These measures included use of remote monitoring, remote diagnostics, telehealth visits, and modified symptom monitoring.
Effective strategies that increased flexibility in time were delayed visits, delayed assessments, and changes to the Institutional Review Board.
The study was funded by the IASLC, which received industry support to conduct the project. Dr. Smeltzer reported no relevant financial relationships. Dr. Garassino has relationships with AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Ignyta, Incyte, MedImmune, Mirati, MSD International, Novartis, Pfizer, Regeneron, Roche, Takeda, and Seattle Genetics.
A version of this article first appeared on Medscape.com.
Air pollution – second leading cause of lung cancer
The new data show that the rate of lung cancer deaths attributable to air pollution varies widely between countries. Serbia, Poland, China, Mongolia, and Turkey are among the worst affected. The analysis shows an association between deaths from lung cancer and the proportion of national energy that is produced from coal.
“Both smoking and air pollution are important causes of lung cancer,” said study presenter Christine D. Berg, MD, former codirector of the National Lung Screening Trial, and “both need to be eliminated to help prevent lung cancer and save lives.
“As lung cancer professionals, we can mitigate the effects of air pollution on causing lung cancer by speaking out for clean energy standards,” she said.
Dr. Berg presented the new analysis on Sept. 9 at the 2021 World Conference on Lung Cancer, which was organized by the International Association for the Study of Lung Cancer.
She welcomed the recent statement issued by the IASLC in support of the International Day of Clean Air for Blue Skies, which took place on Sept. 7. It was a call for action that emphasized the need for further efforts to improve air quality to protect human health.
The findings from the new analysis are “depressing,” commented Joachim G. J. V. Aerts, MD. PhD, department of pulmonary diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.
It is now clear that air pollution has an impact not only on the incidence of lung cancer but also on its outcome, he added.
Indeed, previous research showed that each 10 mcg/m3 increase in particular matter of 2.5 mcg in size was associated with a 15%-27% increase in lung cancer mortality. There was no difference in rates between women and men.
A key question, Dr. Aerts said, is whether reducing air pollution would be beneficial.
Efforts to reduce air pollution over recent decades in the United Kingdom have not led to a reduction in lung cancer deaths. This is because of the increase in life expectancy – individuals have been exposed to pollution for longer, albeit at lower levels, he pointed out.
Because of lockdowns during the COVID pandemic, travel has been greatly reduced. This has resulted in a dramatic reduction in air pollution, “and this led to a decrease in the number of children born with low birth weight,” said Dr. Aerts.
Hopefully, that benefit will also be seen regarding other diseases, he added.
The call to action to reduce air pollution is of the “utmost importance,” he said. He noted that the focus should be on global, national, local, and personal preventive measures.
“It is time to join forces,” he added, “to ‘clean the air.’ ”
Dr. Berg’s presentation was warmly received on social media.
It was “fabulous,” commented Eric H. Bernicker, MD, director of medical thoracic oncology at Houston Methodist Cancer Center.
“Thoracic oncologists need to add air pollution to things they advocate about; we have an important voice here,” he added.
It is “so important to understand that air pollution is a human carcinogen,” commented Ivy Elkins, a lung cancer survivor and advocate and cofounder of the EGFR Resisters Lung Cancer Patient Group. “All you need are lungs to get lung cancer!”
Contribution of air pollution to lung cancer
In her presentation, Dr. Berg emphasized that lung cancer is the leading cause of cancer death worldwide, although the distribution between countries “depends on historical and current smoking patterns and the demographics of the population.”
Overall, data from GLOBOCAN 2018 indicate that annually there are approximately 2.1 million incident cases of lung cancer and almost 1.8 million lung cancer deaths around the globe.
A recent study estimated that, worldwide, 14.1% of all lung cancer deaths, including in never-smokers, are directly linked to air pollution.
Dr. Berg said that this makes it the “second-leading cause of lung cancer” behind smoking.
The figure is somewhat lower for the United States, where around 4.7% of lung cancer deaths each year are directly attributable to pollution. However, with “the wildfires out West, we’re going to be seeing more of a toll from air pollution,” she predicted.
She pointed out that the International Agency for Research on Cancer classifies outdoor air pollution, especially particulate matter, as a human carcinogen on the basis of evidence of an association with lung cancer.
It is thought that direct deposits and local effects of particulate matter lead to oxidative damage and low-grade chronic inflammation. These in turn result in molecular changes that affect DNA and gene transcription and inhibit apoptosis, all of which lead to the development of cancerous lesions, she explained.
Synthesizing various estimates on global burden of disease, Dr. Berg and colleagues calculated that in 2019 the rate of lung cancer deaths attributable to particular matter in people aged 50-69 years was highest in Serbia, at 36.88 attributable deaths per 100,000.
Next was Poland, with a rate of 27.97 per 100,000, followed by China at 24.63 per 100,000, Mongolia at 19.71 per 100,000, and Turkey at 19.2 per 100,000.
The major sources of air pollution in the most affected countries were transportation, indoor cooking, and energy sources, she said.
In Serbia, 70% of energy production was from coal. It was 74% in Poland, 65% in China, 80% in Mongolia, 35% in Turkey, and 19% in the United States.
At the time of the analysis, only 17.3% of U.S. adults were smokers, and the air concentration of particular matter of 2.5 mcm was 9.6% mcg/m3. Both of these rates are far below those seen in more severely affected countries.
“But 40% of our energy now comes from natural gas,” noted Dr. Berg, “which is still a pollutant and a source of methane. It’s a very potent greenhouse gas.”
No funding for the study has been reported. Dr. Berg has relationships with GRAIL and Mercy BioAnalytics. Dr. Aerts has relationships with Amphera, AstraZeneca, Bayer, BIOCAD, Bristol-Myers Squibb, Eli Lilly, and Roche.
A version of this article first appeared on Medscape.com.
The new data show that the rate of lung cancer deaths attributable to air pollution varies widely between countries. Serbia, Poland, China, Mongolia, and Turkey are among the worst affected. The analysis shows an association between deaths from lung cancer and the proportion of national energy that is produced from coal.
“Both smoking and air pollution are important causes of lung cancer,” said study presenter Christine D. Berg, MD, former codirector of the National Lung Screening Trial, and “both need to be eliminated to help prevent lung cancer and save lives.
“As lung cancer professionals, we can mitigate the effects of air pollution on causing lung cancer by speaking out for clean energy standards,” she said.
Dr. Berg presented the new analysis on Sept. 9 at the 2021 World Conference on Lung Cancer, which was organized by the International Association for the Study of Lung Cancer.
She welcomed the recent statement issued by the IASLC in support of the International Day of Clean Air for Blue Skies, which took place on Sept. 7. It was a call for action that emphasized the need for further efforts to improve air quality to protect human health.
The findings from the new analysis are “depressing,” commented Joachim G. J. V. Aerts, MD. PhD, department of pulmonary diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.
It is now clear that air pollution has an impact not only on the incidence of lung cancer but also on its outcome, he added.
Indeed, previous research showed that each 10 mcg/m3 increase in particular matter of 2.5 mcg in size was associated with a 15%-27% increase in lung cancer mortality. There was no difference in rates between women and men.
A key question, Dr. Aerts said, is whether reducing air pollution would be beneficial.
Efforts to reduce air pollution over recent decades in the United Kingdom have not led to a reduction in lung cancer deaths. This is because of the increase in life expectancy – individuals have been exposed to pollution for longer, albeit at lower levels, he pointed out.
Because of lockdowns during the COVID pandemic, travel has been greatly reduced. This has resulted in a dramatic reduction in air pollution, “and this led to a decrease in the number of children born with low birth weight,” said Dr. Aerts.
Hopefully, that benefit will also be seen regarding other diseases, he added.
The call to action to reduce air pollution is of the “utmost importance,” he said. He noted that the focus should be on global, national, local, and personal preventive measures.
“It is time to join forces,” he added, “to ‘clean the air.’ ”
Dr. Berg’s presentation was warmly received on social media.
It was “fabulous,” commented Eric H. Bernicker, MD, director of medical thoracic oncology at Houston Methodist Cancer Center.
“Thoracic oncologists need to add air pollution to things they advocate about; we have an important voice here,” he added.
It is “so important to understand that air pollution is a human carcinogen,” commented Ivy Elkins, a lung cancer survivor and advocate and cofounder of the EGFR Resisters Lung Cancer Patient Group. “All you need are lungs to get lung cancer!”
Contribution of air pollution to lung cancer
In her presentation, Dr. Berg emphasized that lung cancer is the leading cause of cancer death worldwide, although the distribution between countries “depends on historical and current smoking patterns and the demographics of the population.”
Overall, data from GLOBOCAN 2018 indicate that annually there are approximately 2.1 million incident cases of lung cancer and almost 1.8 million lung cancer deaths around the globe.
A recent study estimated that, worldwide, 14.1% of all lung cancer deaths, including in never-smokers, are directly linked to air pollution.
Dr. Berg said that this makes it the “second-leading cause of lung cancer” behind smoking.
The figure is somewhat lower for the United States, where around 4.7% of lung cancer deaths each year are directly attributable to pollution. However, with “the wildfires out West, we’re going to be seeing more of a toll from air pollution,” she predicted.
She pointed out that the International Agency for Research on Cancer classifies outdoor air pollution, especially particulate matter, as a human carcinogen on the basis of evidence of an association with lung cancer.
It is thought that direct deposits and local effects of particulate matter lead to oxidative damage and low-grade chronic inflammation. These in turn result in molecular changes that affect DNA and gene transcription and inhibit apoptosis, all of which lead to the development of cancerous lesions, she explained.
Synthesizing various estimates on global burden of disease, Dr. Berg and colleagues calculated that in 2019 the rate of lung cancer deaths attributable to particular matter in people aged 50-69 years was highest in Serbia, at 36.88 attributable deaths per 100,000.
Next was Poland, with a rate of 27.97 per 100,000, followed by China at 24.63 per 100,000, Mongolia at 19.71 per 100,000, and Turkey at 19.2 per 100,000.
The major sources of air pollution in the most affected countries were transportation, indoor cooking, and energy sources, she said.
In Serbia, 70% of energy production was from coal. It was 74% in Poland, 65% in China, 80% in Mongolia, 35% in Turkey, and 19% in the United States.
At the time of the analysis, only 17.3% of U.S. adults were smokers, and the air concentration of particular matter of 2.5 mcm was 9.6% mcg/m3. Both of these rates are far below those seen in more severely affected countries.
“But 40% of our energy now comes from natural gas,” noted Dr. Berg, “which is still a pollutant and a source of methane. It’s a very potent greenhouse gas.”
No funding for the study has been reported. Dr. Berg has relationships with GRAIL and Mercy BioAnalytics. Dr. Aerts has relationships with Amphera, AstraZeneca, Bayer, BIOCAD, Bristol-Myers Squibb, Eli Lilly, and Roche.
A version of this article first appeared on Medscape.com.
The new data show that the rate of lung cancer deaths attributable to air pollution varies widely between countries. Serbia, Poland, China, Mongolia, and Turkey are among the worst affected. The analysis shows an association between deaths from lung cancer and the proportion of national energy that is produced from coal.
“Both smoking and air pollution are important causes of lung cancer,” said study presenter Christine D. Berg, MD, former codirector of the National Lung Screening Trial, and “both need to be eliminated to help prevent lung cancer and save lives.
“As lung cancer professionals, we can mitigate the effects of air pollution on causing lung cancer by speaking out for clean energy standards,” she said.
Dr. Berg presented the new analysis on Sept. 9 at the 2021 World Conference on Lung Cancer, which was organized by the International Association for the Study of Lung Cancer.
She welcomed the recent statement issued by the IASLC in support of the International Day of Clean Air for Blue Skies, which took place on Sept. 7. It was a call for action that emphasized the need for further efforts to improve air quality to protect human health.
The findings from the new analysis are “depressing,” commented Joachim G. J. V. Aerts, MD. PhD, department of pulmonary diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.
It is now clear that air pollution has an impact not only on the incidence of lung cancer but also on its outcome, he added.
Indeed, previous research showed that each 10 mcg/m3 increase in particular matter of 2.5 mcg in size was associated with a 15%-27% increase in lung cancer mortality. There was no difference in rates between women and men.
A key question, Dr. Aerts said, is whether reducing air pollution would be beneficial.
Efforts to reduce air pollution over recent decades in the United Kingdom have not led to a reduction in lung cancer deaths. This is because of the increase in life expectancy – individuals have been exposed to pollution for longer, albeit at lower levels, he pointed out.
Because of lockdowns during the COVID pandemic, travel has been greatly reduced. This has resulted in a dramatic reduction in air pollution, “and this led to a decrease in the number of children born with low birth weight,” said Dr. Aerts.
Hopefully, that benefit will also be seen regarding other diseases, he added.
The call to action to reduce air pollution is of the “utmost importance,” he said. He noted that the focus should be on global, national, local, and personal preventive measures.
“It is time to join forces,” he added, “to ‘clean the air.’ ”
Dr. Berg’s presentation was warmly received on social media.
It was “fabulous,” commented Eric H. Bernicker, MD, director of medical thoracic oncology at Houston Methodist Cancer Center.
“Thoracic oncologists need to add air pollution to things they advocate about; we have an important voice here,” he added.
It is “so important to understand that air pollution is a human carcinogen,” commented Ivy Elkins, a lung cancer survivor and advocate and cofounder of the EGFR Resisters Lung Cancer Patient Group. “All you need are lungs to get lung cancer!”
Contribution of air pollution to lung cancer
In her presentation, Dr. Berg emphasized that lung cancer is the leading cause of cancer death worldwide, although the distribution between countries “depends on historical and current smoking patterns and the demographics of the population.”
Overall, data from GLOBOCAN 2018 indicate that annually there are approximately 2.1 million incident cases of lung cancer and almost 1.8 million lung cancer deaths around the globe.
A recent study estimated that, worldwide, 14.1% of all lung cancer deaths, including in never-smokers, are directly linked to air pollution.
Dr. Berg said that this makes it the “second-leading cause of lung cancer” behind smoking.
The figure is somewhat lower for the United States, where around 4.7% of lung cancer deaths each year are directly attributable to pollution. However, with “the wildfires out West, we’re going to be seeing more of a toll from air pollution,” she predicted.
She pointed out that the International Agency for Research on Cancer classifies outdoor air pollution, especially particulate matter, as a human carcinogen on the basis of evidence of an association with lung cancer.
It is thought that direct deposits and local effects of particulate matter lead to oxidative damage and low-grade chronic inflammation. These in turn result in molecular changes that affect DNA and gene transcription and inhibit apoptosis, all of which lead to the development of cancerous lesions, she explained.
Synthesizing various estimates on global burden of disease, Dr. Berg and colleagues calculated that in 2019 the rate of lung cancer deaths attributable to particular matter in people aged 50-69 years was highest in Serbia, at 36.88 attributable deaths per 100,000.
Next was Poland, with a rate of 27.97 per 100,000, followed by China at 24.63 per 100,000, Mongolia at 19.71 per 100,000, and Turkey at 19.2 per 100,000.
The major sources of air pollution in the most affected countries were transportation, indoor cooking, and energy sources, she said.
In Serbia, 70% of energy production was from coal. It was 74% in Poland, 65% in China, 80% in Mongolia, 35% in Turkey, and 19% in the United States.
At the time of the analysis, only 17.3% of U.S. adults were smokers, and the air concentration of particular matter of 2.5 mcm was 9.6% mcg/m3. Both of these rates are far below those seen in more severely affected countries.
“But 40% of our energy now comes from natural gas,” noted Dr. Berg, “which is still a pollutant and a source of methane. It’s a very potent greenhouse gas.”
No funding for the study has been reported. Dr. Berg has relationships with GRAIL and Mercy BioAnalytics. Dr. Aerts has relationships with Amphera, AstraZeneca, Bayer, BIOCAD, Bristol-Myers Squibb, Eli Lilly, and Roche.
A version of this article first appeared on Medscape.com.
Unequal resource distribution underlies lung cancer disparities
Lung cancer disparities are reversible, but it will take changes at the social policy and organizational levels to do it, according to Ray Osarogiagbon, MBBS, a medical oncologist in the thoracic oncology program at Baptist Cancer Center, Memphis.
Much of the issue comes down to unequal distribution of services across the country, with less high-end care available in areas hardest hit by lung cancer, which are often areas with higher percentages of Black people, Dr. Osarogiagbon said. He addressed the issues – which he conceptualizes as “avoidable differences” – in a plenary presentation at the virtual 2021 World Conference on Lung Cancer.
He said that much of disparity research has focused on patient-level issues, but it has the least potential to effect change and also has “the unpleasant side effect of stigmatizing the victims of disparate health care delivery.”
Better to look at the big picture. “We have to focus on the areas where we are most likely to be successful, the social policy level, next the organizational level, and then providers,” he said.
Kentucky, followed by Mississippi, Arkansas, Tennessee, West Virginia, and Alabama, has the highest lung cancer burden in the United States. While lung cancer has been on the decline for decades nationwide, some counties in those states in particular continue to struggle with rising lung cancer mortality.
Dr. Osarogiagbon’s own health care system, which serves western Tennessee as well as eastern Arkansas and northern Mississippi, sees about 1,300 lung cancer cases annually, more than many states in the United States.
Regional disparities in lung cancer care span the entirety of available services, from unequal access to tobacco cessation and other preventive measures straight through to access to leading-edge systemic therapies. Disparities are particularly acute with more recent advances such as immunotherapy and low-dose CT screening.
One recent study, for instance, found that several southern states with high lung cancer burdens had screening rates below 4%, while several New England states had rates ranging to over 15%.
“There is a mismatch between the places were lung cancer kills and the places where we have invested in low-dose CT scan facilities,” Dr. Osarogiagbon said. As a side effect, White patients have better access,
It’s not, he said, that Black people are more likely to refuse such services, as least as far as clinical trials go.
Black patients are significantly underrepresented in pharmaceutical industry trials. Part of the issues is that areas hardest hit by lung cancer are often also ones less likely to have the infrastructure to support trials.
But on an equal playing field, Black patients are at least as eager as White patients to sign up for a trial. Dr. Osarogiagbon and colleagues found that, if offered the chance, almost 60% of Black patients said they would participate in a trial versus 53.4% of White patients. If access were equal, there would be “no race-based disparities” in trial participation, he said.
It’s also emerging that Black patients might benefit more from innovations such as immune checkpoint inhibitors treatment and low-dose CT screening, which means that, if they were included in more trials, companies would likely have stronger study results.
It’s something they should pay attention to, if for no other reason than it would help their bottom line, Dr. Osarogiagbon said.
Curative surgery for early-stage lung tumors is another issue. At the county level in the United States, he and his team found that it’s offered to anywhere from 13% to 92% of patients who qualify.
“Counties in the lowest quartile for receipt of surgery were those with a high proportion of non-Hispanic Black subjects, high poverty and uninsured rates, low surgeon-to-population ratio, and nonmetropolitan status,” they found.
Dr. Osarogiagbon is a consultant for and/or has stock in a number of companies, including AstraZeneca, Eli Lilly, and Genentech.
Lung cancer disparities are reversible, but it will take changes at the social policy and organizational levels to do it, according to Ray Osarogiagbon, MBBS, a medical oncologist in the thoracic oncology program at Baptist Cancer Center, Memphis.
Much of the issue comes down to unequal distribution of services across the country, with less high-end care available in areas hardest hit by lung cancer, which are often areas with higher percentages of Black people, Dr. Osarogiagbon said. He addressed the issues – which he conceptualizes as “avoidable differences” – in a plenary presentation at the virtual 2021 World Conference on Lung Cancer.
He said that much of disparity research has focused on patient-level issues, but it has the least potential to effect change and also has “the unpleasant side effect of stigmatizing the victims of disparate health care delivery.”
Better to look at the big picture. “We have to focus on the areas where we are most likely to be successful, the social policy level, next the organizational level, and then providers,” he said.
Kentucky, followed by Mississippi, Arkansas, Tennessee, West Virginia, and Alabama, has the highest lung cancer burden in the United States. While lung cancer has been on the decline for decades nationwide, some counties in those states in particular continue to struggle with rising lung cancer mortality.
Dr. Osarogiagbon’s own health care system, which serves western Tennessee as well as eastern Arkansas and northern Mississippi, sees about 1,300 lung cancer cases annually, more than many states in the United States.
Regional disparities in lung cancer care span the entirety of available services, from unequal access to tobacco cessation and other preventive measures straight through to access to leading-edge systemic therapies. Disparities are particularly acute with more recent advances such as immunotherapy and low-dose CT screening.
One recent study, for instance, found that several southern states with high lung cancer burdens had screening rates below 4%, while several New England states had rates ranging to over 15%.
“There is a mismatch between the places were lung cancer kills and the places where we have invested in low-dose CT scan facilities,” Dr. Osarogiagbon said. As a side effect, White patients have better access,
It’s not, he said, that Black people are more likely to refuse such services, as least as far as clinical trials go.
Black patients are significantly underrepresented in pharmaceutical industry trials. Part of the issues is that areas hardest hit by lung cancer are often also ones less likely to have the infrastructure to support trials.
But on an equal playing field, Black patients are at least as eager as White patients to sign up for a trial. Dr. Osarogiagbon and colleagues found that, if offered the chance, almost 60% of Black patients said they would participate in a trial versus 53.4% of White patients. If access were equal, there would be “no race-based disparities” in trial participation, he said.
It’s also emerging that Black patients might benefit more from innovations such as immune checkpoint inhibitors treatment and low-dose CT screening, which means that, if they were included in more trials, companies would likely have stronger study results.
It’s something they should pay attention to, if for no other reason than it would help their bottom line, Dr. Osarogiagbon said.
Curative surgery for early-stage lung tumors is another issue. At the county level in the United States, he and his team found that it’s offered to anywhere from 13% to 92% of patients who qualify.
“Counties in the lowest quartile for receipt of surgery were those with a high proportion of non-Hispanic Black subjects, high poverty and uninsured rates, low surgeon-to-population ratio, and nonmetropolitan status,” they found.
Dr. Osarogiagbon is a consultant for and/or has stock in a number of companies, including AstraZeneca, Eli Lilly, and Genentech.
Lung cancer disparities are reversible, but it will take changes at the social policy and organizational levels to do it, according to Ray Osarogiagbon, MBBS, a medical oncologist in the thoracic oncology program at Baptist Cancer Center, Memphis.
Much of the issue comes down to unequal distribution of services across the country, with less high-end care available in areas hardest hit by lung cancer, which are often areas with higher percentages of Black people, Dr. Osarogiagbon said. He addressed the issues – which he conceptualizes as “avoidable differences” – in a plenary presentation at the virtual 2021 World Conference on Lung Cancer.
He said that much of disparity research has focused on patient-level issues, but it has the least potential to effect change and also has “the unpleasant side effect of stigmatizing the victims of disparate health care delivery.”
Better to look at the big picture. “We have to focus on the areas where we are most likely to be successful, the social policy level, next the organizational level, and then providers,” he said.
Kentucky, followed by Mississippi, Arkansas, Tennessee, West Virginia, and Alabama, has the highest lung cancer burden in the United States. While lung cancer has been on the decline for decades nationwide, some counties in those states in particular continue to struggle with rising lung cancer mortality.
Dr. Osarogiagbon’s own health care system, which serves western Tennessee as well as eastern Arkansas and northern Mississippi, sees about 1,300 lung cancer cases annually, more than many states in the United States.
Regional disparities in lung cancer care span the entirety of available services, from unequal access to tobacco cessation and other preventive measures straight through to access to leading-edge systemic therapies. Disparities are particularly acute with more recent advances such as immunotherapy and low-dose CT screening.
One recent study, for instance, found that several southern states with high lung cancer burdens had screening rates below 4%, while several New England states had rates ranging to over 15%.
“There is a mismatch between the places were lung cancer kills and the places where we have invested in low-dose CT scan facilities,” Dr. Osarogiagbon said. As a side effect, White patients have better access,
It’s not, he said, that Black people are more likely to refuse such services, as least as far as clinical trials go.
Black patients are significantly underrepresented in pharmaceutical industry trials. Part of the issues is that areas hardest hit by lung cancer are often also ones less likely to have the infrastructure to support trials.
But on an equal playing field, Black patients are at least as eager as White patients to sign up for a trial. Dr. Osarogiagbon and colleagues found that, if offered the chance, almost 60% of Black patients said they would participate in a trial versus 53.4% of White patients. If access were equal, there would be “no race-based disparities” in trial participation, he said.
It’s also emerging that Black patients might benefit more from innovations such as immune checkpoint inhibitors treatment and low-dose CT screening, which means that, if they were included in more trials, companies would likely have stronger study results.
It’s something they should pay attention to, if for no other reason than it would help their bottom line, Dr. Osarogiagbon said.
Curative surgery for early-stage lung tumors is another issue. At the county level in the United States, he and his team found that it’s offered to anywhere from 13% to 92% of patients who qualify.
“Counties in the lowest quartile for receipt of surgery were those with a high proportion of non-Hispanic Black subjects, high poverty and uninsured rates, low surgeon-to-population ratio, and nonmetropolitan status,” they found.
Dr. Osarogiagbon is a consultant for and/or has stock in a number of companies, including AstraZeneca, Eli Lilly, and Genentech.
FROM WCLC 2021
Finding the most bang for the buck with adjuvant atezolizumab for NSCLC
Investigators are zeroing in on the stage II-IIIa non–small cell lung cancer patients most likely to benefit from adjuvant atezolizumab (Tecentriq) following resection and chemotherapy.
It seems that PD-L1 positive patients, those who undergo lobectomy, those who have nodal involvement, and those treated with all common platinum doublets, with the possible exception of cisplatin-gemcitabine, are most likely to benefit from adjuvant treatment, according to a report at the virtual 2021 World Congress on Lung Cancer.
Results come for an analysis of IMpower010, which randomized 1,005 patients equally to either best supportive care or atezolizumab every 21 days for 16 cycles following resection and chemotherapy.
The topline results, reported recently, found a 34% improvement in disease-free survival (DFS) in stage II-IIIa patients expressing PD-L1 and a 21% improvement across all patients regardless of PD-L1 expression.
It was the first positive phase 3 trial for adjuvant immunotherapy in NSCLC. Maker Hoffman-La Roche subsequently applied to the U.S. Food and Drug Administration for an indication for adjuvant treatment following surgery and platinum-based chemotherapy for NSCLC with PD-L1 expression of at least 1%.
At the WCLC meeting, investigators took a closer look at IMpower010 to gauge the impact of different surgery and chemotherapy types on outcomes.
“Improved DFS was observed with adjuvant atezolizumab” for II-IIIa disease across most stages in patients “with nodal involvement, and across most surgery resection types and chemotherapy regimens,” said lead investigator Nasser Altorki, MD, director of the division of thoracic surgery at New York Presbyterian-Weill Cornell Medical Center in New York.
Study discussant Ichiro Yoshino, MD, PhD, a thoracic surgeon at Chiba University, in Japan, expanded on the “most” part of the assertion.
“Patients who underwent lobectomy [78%] had more evident benefit. … Patients who had a pneumonectomy [16%] did not benefit from atezolizumab,” he said (DFS hazard ratio, 0.91, 95% confidence interval, 0.56-1.47).
The reasons are unclear. It could be because patients who have pneumonectomies are less tolerant of adjuvant chemotherapy, so might have not gotten complete courses, but whatever the cause, Dr. Yoshino said it’s an important finding that needs further investigation.
Also, there was no DFS benefit in the 16% of patients who received cisplatin-gemcitabine for chemotherapy instead of other platinum doublets (HR, 0.94, 95% CI, 0.56-1.57).
It might have to do with the fact that under 80% of cisplatin-gemcitabine patients completed all four cycles of chemotherapy versus completion rates of up to more than 90% with other platinum doublets. It might also, however, have something to do with the way gemcitabine works or its interaction with atezolizumab.
The issue is another one that needs “to be examined,” Dr. Yoshino said.
The trial was funded by Hoffman-La Roche. Dr. Altorki is an advisor and/or researcher for AstraZeneca, Merck, and Johnson & Johnson. Among various company ties, Dr. Yoshino is an advisor and speaker for AstraZeneca and Johnson & Johnson and a researcher for Pfizer.
Investigators are zeroing in on the stage II-IIIa non–small cell lung cancer patients most likely to benefit from adjuvant atezolizumab (Tecentriq) following resection and chemotherapy.
It seems that PD-L1 positive patients, those who undergo lobectomy, those who have nodal involvement, and those treated with all common platinum doublets, with the possible exception of cisplatin-gemcitabine, are most likely to benefit from adjuvant treatment, according to a report at the virtual 2021 World Congress on Lung Cancer.
Results come for an analysis of IMpower010, which randomized 1,005 patients equally to either best supportive care or atezolizumab every 21 days for 16 cycles following resection and chemotherapy.
The topline results, reported recently, found a 34% improvement in disease-free survival (DFS) in stage II-IIIa patients expressing PD-L1 and a 21% improvement across all patients regardless of PD-L1 expression.
It was the first positive phase 3 trial for adjuvant immunotherapy in NSCLC. Maker Hoffman-La Roche subsequently applied to the U.S. Food and Drug Administration for an indication for adjuvant treatment following surgery and platinum-based chemotherapy for NSCLC with PD-L1 expression of at least 1%.
At the WCLC meeting, investigators took a closer look at IMpower010 to gauge the impact of different surgery and chemotherapy types on outcomes.
“Improved DFS was observed with adjuvant atezolizumab” for II-IIIa disease across most stages in patients “with nodal involvement, and across most surgery resection types and chemotherapy regimens,” said lead investigator Nasser Altorki, MD, director of the division of thoracic surgery at New York Presbyterian-Weill Cornell Medical Center in New York.
Study discussant Ichiro Yoshino, MD, PhD, a thoracic surgeon at Chiba University, in Japan, expanded on the “most” part of the assertion.
“Patients who underwent lobectomy [78%] had more evident benefit. … Patients who had a pneumonectomy [16%] did not benefit from atezolizumab,” he said (DFS hazard ratio, 0.91, 95% confidence interval, 0.56-1.47).
The reasons are unclear. It could be because patients who have pneumonectomies are less tolerant of adjuvant chemotherapy, so might have not gotten complete courses, but whatever the cause, Dr. Yoshino said it’s an important finding that needs further investigation.
Also, there was no DFS benefit in the 16% of patients who received cisplatin-gemcitabine for chemotherapy instead of other platinum doublets (HR, 0.94, 95% CI, 0.56-1.57).
It might have to do with the fact that under 80% of cisplatin-gemcitabine patients completed all four cycles of chemotherapy versus completion rates of up to more than 90% with other platinum doublets. It might also, however, have something to do with the way gemcitabine works or its interaction with atezolizumab.
The issue is another one that needs “to be examined,” Dr. Yoshino said.
The trial was funded by Hoffman-La Roche. Dr. Altorki is an advisor and/or researcher for AstraZeneca, Merck, and Johnson & Johnson. Among various company ties, Dr. Yoshino is an advisor and speaker for AstraZeneca and Johnson & Johnson and a researcher for Pfizer.
Investigators are zeroing in on the stage II-IIIa non–small cell lung cancer patients most likely to benefit from adjuvant atezolizumab (Tecentriq) following resection and chemotherapy.
It seems that PD-L1 positive patients, those who undergo lobectomy, those who have nodal involvement, and those treated with all common platinum doublets, with the possible exception of cisplatin-gemcitabine, are most likely to benefit from adjuvant treatment, according to a report at the virtual 2021 World Congress on Lung Cancer.
Results come for an analysis of IMpower010, which randomized 1,005 patients equally to either best supportive care or atezolizumab every 21 days for 16 cycles following resection and chemotherapy.
The topline results, reported recently, found a 34% improvement in disease-free survival (DFS) in stage II-IIIa patients expressing PD-L1 and a 21% improvement across all patients regardless of PD-L1 expression.
It was the first positive phase 3 trial for adjuvant immunotherapy in NSCLC. Maker Hoffman-La Roche subsequently applied to the U.S. Food and Drug Administration for an indication for adjuvant treatment following surgery and platinum-based chemotherapy for NSCLC with PD-L1 expression of at least 1%.
At the WCLC meeting, investigators took a closer look at IMpower010 to gauge the impact of different surgery and chemotherapy types on outcomes.
“Improved DFS was observed with adjuvant atezolizumab” for II-IIIa disease across most stages in patients “with nodal involvement, and across most surgery resection types and chemotherapy regimens,” said lead investigator Nasser Altorki, MD, director of the division of thoracic surgery at New York Presbyterian-Weill Cornell Medical Center in New York.
Study discussant Ichiro Yoshino, MD, PhD, a thoracic surgeon at Chiba University, in Japan, expanded on the “most” part of the assertion.
“Patients who underwent lobectomy [78%] had more evident benefit. … Patients who had a pneumonectomy [16%] did not benefit from atezolizumab,” he said (DFS hazard ratio, 0.91, 95% confidence interval, 0.56-1.47).
The reasons are unclear. It could be because patients who have pneumonectomies are less tolerant of adjuvant chemotherapy, so might have not gotten complete courses, but whatever the cause, Dr. Yoshino said it’s an important finding that needs further investigation.
Also, there was no DFS benefit in the 16% of patients who received cisplatin-gemcitabine for chemotherapy instead of other platinum doublets (HR, 0.94, 95% CI, 0.56-1.57).
It might have to do with the fact that under 80% of cisplatin-gemcitabine patients completed all four cycles of chemotherapy versus completion rates of up to more than 90% with other platinum doublets. It might also, however, have something to do with the way gemcitabine works or its interaction with atezolizumab.
The issue is another one that needs “to be examined,” Dr. Yoshino said.
The trial was funded by Hoffman-La Roche. Dr. Altorki is an advisor and/or researcher for AstraZeneca, Merck, and Johnson & Johnson. Among various company ties, Dr. Yoshino is an advisor and speaker for AstraZeneca and Johnson & Johnson and a researcher for Pfizer.
FROM WCLC 2021
Microwave ablation an alternative therapy in lung malignancy
Lung cancer patients with relatively small nodules who cannot or will not undergo surgery or radiotherapy can be successfully treated with targeted transbronchial microwave ablation, indicate results from a U.K.-led preliminary trial.
The NAVABLATE study included 30 patients from the U.K. and Hong Kong who had malignant lung nodules no more than 30 mm in diameter, who underwent transbronchial microwave ablation and were followed up one month later.
On the day, the technique was performed successfully in all 30 patients, while follow-up imaging at one month suggested that the ablation had been satisfactory in every case, with no repeat procedures necessary.
It was also associated with a “low rate of device-related adverse events and no serious adverse events,” said lead author Kevin Lau, Barts Thorax Centre, St. Bartholomew’s Hospital, Barts Health NHS Trust, London.
Consequently, transbronchial microwave ablation can be considered “an alternative treatment modality for patients with primary and metastatic malignant lung nodules … who decline or are ineligible” for surgery and radiotherapy.
The research was presented at the European Respiratory Society International Congress (ERS) 2021 on September 5.
‘Encouraging’ results
Professor Stefano Elia, head of the European Respiratory Society’s Assembly on Thoracic Surgery and Transplantation, told this news organization that the results “are encouraging.”
However, the patient numbers are “very low, so it is difficult to draw value conclusions,” and he would like to have seen more detailed characterization of the patients’ tumors.
Prof. Elia, from the University of Rome Tor Vergata, added that transbronchial microwave ablation should, in line with the study’s inclusion criteria, “probably be reserved” for lung cancer patients “who are unfit for or refuse surgery or alternative treatment strategies.”
He added that “prospective, randomized trials are warranted to see if the technique is feasible, safe and indicated” in these patients, and the potential cost of performing it needs to be specified.
Study details
Presenting the study, Mr. Lau explained that NAVABLATE was a prospective, multicenter study that enrolled patients with a confirmed malignant lung nodule ≤30 mm that did not abut the pleura, fissure, or critical structures.
In addition, the patients had declined or were not eligible for both surgery and stereotactic body radiotherapy.
They underwent transbronchial microwave ablation with the Emprint ablation catheter (Medtronic) in a hybrid theatre while undergoing cone-beam computed tomography. Only one nodule was ablated if the patients had more than one.
The team recruited 30 patients at two centres in the U.K. and Hong Kong, who had a mean age of 68.4 years and of whom 40% were female. The majority (66.7%) were prior or current tobacco users.
Primary lung cancer was the diagnosis in 20 patients, while 10 had oligometastatic disease, and the median nodule size was 12.5 mm. Thirty percent of patients had previously undergone lobectomy and 16.7% wedge resection.
Thirty-nine ablations were performed in the 30 patients, with 22 having a single ablation. Two ablations were performed in seven patients, while one had three ablations.
The most common ablation times were 10 minutes, in 21 procedures, and 7 minutes, in eight procedures, and the average total bronchoscopy time was 127 minutes.
Technical success
The procedure was deemed a technical success, defined as the nodule being reached and ablated according to the study protocol, in all patients.
The average ablation margin was 9.9 mm, and 1-month follow-up imaging was performed in all patients. This revealed a satisfactory ablation in 100% of cases. No patients required retreatment.
One patient had an adverse event relating to the ablation itself over the one-month follow-up, consisting of grade 1 mild haemoptysis on day 5, which self-resolved.
Adverse events relating to any aspect of the bronchoscopy were seen in 70% of patients, while 13.3% had grade ≥3 events, These included post-procedure pleuritic chest pain in two patients, pleural effusion in two patients, post-ablation syndrome in one patient, and ablation site infection in one patient, all grade 3.
The researchers found that the patients reported only mild pain immediately post-procedure, at an average score of 1.5 on a 10-point scale, falling to 1.4 one week later. At one month, the average pain score was 0.5.
Quality of life, as measured on the EQ-5D-3L was unaffected by the procedure, with scores rising slightly from 74.6 at baseline to 77.4 at the one-month follow-up.
The study was sponsored and funded by Medtronic.
Mr. Lau declares relationships with Medtronic, Philips, and Johnson & Johnson.
A version of this article first appeared on Medscape.com.
Lung cancer patients with relatively small nodules who cannot or will not undergo surgery or radiotherapy can be successfully treated with targeted transbronchial microwave ablation, indicate results from a U.K.-led preliminary trial.
The NAVABLATE study included 30 patients from the U.K. and Hong Kong who had malignant lung nodules no more than 30 mm in diameter, who underwent transbronchial microwave ablation and were followed up one month later.
On the day, the technique was performed successfully in all 30 patients, while follow-up imaging at one month suggested that the ablation had been satisfactory in every case, with no repeat procedures necessary.
It was also associated with a “low rate of device-related adverse events and no serious adverse events,” said lead author Kevin Lau, Barts Thorax Centre, St. Bartholomew’s Hospital, Barts Health NHS Trust, London.
Consequently, transbronchial microwave ablation can be considered “an alternative treatment modality for patients with primary and metastatic malignant lung nodules … who decline or are ineligible” for surgery and radiotherapy.
The research was presented at the European Respiratory Society International Congress (ERS) 2021 on September 5.
‘Encouraging’ results
Professor Stefano Elia, head of the European Respiratory Society’s Assembly on Thoracic Surgery and Transplantation, told this news organization that the results “are encouraging.”
However, the patient numbers are “very low, so it is difficult to draw value conclusions,” and he would like to have seen more detailed characterization of the patients’ tumors.
Prof. Elia, from the University of Rome Tor Vergata, added that transbronchial microwave ablation should, in line with the study’s inclusion criteria, “probably be reserved” for lung cancer patients “who are unfit for or refuse surgery or alternative treatment strategies.”
He added that “prospective, randomized trials are warranted to see if the technique is feasible, safe and indicated” in these patients, and the potential cost of performing it needs to be specified.
Study details
Presenting the study, Mr. Lau explained that NAVABLATE was a prospective, multicenter study that enrolled patients with a confirmed malignant lung nodule ≤30 mm that did not abut the pleura, fissure, or critical structures.
In addition, the patients had declined or were not eligible for both surgery and stereotactic body radiotherapy.
They underwent transbronchial microwave ablation with the Emprint ablation catheter (Medtronic) in a hybrid theatre while undergoing cone-beam computed tomography. Only one nodule was ablated if the patients had more than one.
The team recruited 30 patients at two centres in the U.K. and Hong Kong, who had a mean age of 68.4 years and of whom 40% were female. The majority (66.7%) were prior or current tobacco users.
Primary lung cancer was the diagnosis in 20 patients, while 10 had oligometastatic disease, and the median nodule size was 12.5 mm. Thirty percent of patients had previously undergone lobectomy and 16.7% wedge resection.
Thirty-nine ablations were performed in the 30 patients, with 22 having a single ablation. Two ablations were performed in seven patients, while one had three ablations.
The most common ablation times were 10 minutes, in 21 procedures, and 7 minutes, in eight procedures, and the average total bronchoscopy time was 127 minutes.
Technical success
The procedure was deemed a technical success, defined as the nodule being reached and ablated according to the study protocol, in all patients.
The average ablation margin was 9.9 mm, and 1-month follow-up imaging was performed in all patients. This revealed a satisfactory ablation in 100% of cases. No patients required retreatment.
One patient had an adverse event relating to the ablation itself over the one-month follow-up, consisting of grade 1 mild haemoptysis on day 5, which self-resolved.
Adverse events relating to any aspect of the bronchoscopy were seen in 70% of patients, while 13.3% had grade ≥3 events, These included post-procedure pleuritic chest pain in two patients, pleural effusion in two patients, post-ablation syndrome in one patient, and ablation site infection in one patient, all grade 3.
The researchers found that the patients reported only mild pain immediately post-procedure, at an average score of 1.5 on a 10-point scale, falling to 1.4 one week later. At one month, the average pain score was 0.5.
Quality of life, as measured on the EQ-5D-3L was unaffected by the procedure, with scores rising slightly from 74.6 at baseline to 77.4 at the one-month follow-up.
The study was sponsored and funded by Medtronic.
Mr. Lau declares relationships with Medtronic, Philips, and Johnson & Johnson.
A version of this article first appeared on Medscape.com.
Lung cancer patients with relatively small nodules who cannot or will not undergo surgery or radiotherapy can be successfully treated with targeted transbronchial microwave ablation, indicate results from a U.K.-led preliminary trial.
The NAVABLATE study included 30 patients from the U.K. and Hong Kong who had malignant lung nodules no more than 30 mm in diameter, who underwent transbronchial microwave ablation and were followed up one month later.
On the day, the technique was performed successfully in all 30 patients, while follow-up imaging at one month suggested that the ablation had been satisfactory in every case, with no repeat procedures necessary.
It was also associated with a “low rate of device-related adverse events and no serious adverse events,” said lead author Kevin Lau, Barts Thorax Centre, St. Bartholomew’s Hospital, Barts Health NHS Trust, London.
Consequently, transbronchial microwave ablation can be considered “an alternative treatment modality for patients with primary and metastatic malignant lung nodules … who decline or are ineligible” for surgery and radiotherapy.
The research was presented at the European Respiratory Society International Congress (ERS) 2021 on September 5.
‘Encouraging’ results
Professor Stefano Elia, head of the European Respiratory Society’s Assembly on Thoracic Surgery and Transplantation, told this news organization that the results “are encouraging.”
However, the patient numbers are “very low, so it is difficult to draw value conclusions,” and he would like to have seen more detailed characterization of the patients’ tumors.
Prof. Elia, from the University of Rome Tor Vergata, added that transbronchial microwave ablation should, in line with the study’s inclusion criteria, “probably be reserved” for lung cancer patients “who are unfit for or refuse surgery or alternative treatment strategies.”
He added that “prospective, randomized trials are warranted to see if the technique is feasible, safe and indicated” in these patients, and the potential cost of performing it needs to be specified.
Study details
Presenting the study, Mr. Lau explained that NAVABLATE was a prospective, multicenter study that enrolled patients with a confirmed malignant lung nodule ≤30 mm that did not abut the pleura, fissure, or critical structures.
In addition, the patients had declined or were not eligible for both surgery and stereotactic body radiotherapy.
They underwent transbronchial microwave ablation with the Emprint ablation catheter (Medtronic) in a hybrid theatre while undergoing cone-beam computed tomography. Only one nodule was ablated if the patients had more than one.
The team recruited 30 patients at two centres in the U.K. and Hong Kong, who had a mean age of 68.4 years and of whom 40% were female. The majority (66.7%) were prior or current tobacco users.
Primary lung cancer was the diagnosis in 20 patients, while 10 had oligometastatic disease, and the median nodule size was 12.5 mm. Thirty percent of patients had previously undergone lobectomy and 16.7% wedge resection.
Thirty-nine ablations were performed in the 30 patients, with 22 having a single ablation. Two ablations were performed in seven patients, while one had three ablations.
The most common ablation times were 10 minutes, in 21 procedures, and 7 minutes, in eight procedures, and the average total bronchoscopy time was 127 minutes.
Technical success
The procedure was deemed a technical success, defined as the nodule being reached and ablated according to the study protocol, in all patients.
The average ablation margin was 9.9 mm, and 1-month follow-up imaging was performed in all patients. This revealed a satisfactory ablation in 100% of cases. No patients required retreatment.
One patient had an adverse event relating to the ablation itself over the one-month follow-up, consisting of grade 1 mild haemoptysis on day 5, which self-resolved.
Adverse events relating to any aspect of the bronchoscopy were seen in 70% of patients, while 13.3% had grade ≥3 events, These included post-procedure pleuritic chest pain in two patients, pleural effusion in two patients, post-ablation syndrome in one patient, and ablation site infection in one patient, all grade 3.
The researchers found that the patients reported only mild pain immediately post-procedure, at an average score of 1.5 on a 10-point scale, falling to 1.4 one week later. At one month, the average pain score was 0.5.
Quality of life, as measured on the EQ-5D-3L was unaffected by the procedure, with scores rising slightly from 74.6 at baseline to 77.4 at the one-month follow-up.
The study was sponsored and funded by Medtronic.
Mr. Lau declares relationships with Medtronic, Philips, and Johnson & Johnson.
A version of this article first appeared on Medscape.com.