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Many patients, doctors unaware of advancements in cancer care
This is the main finding from two studies presented at the 2021 European Society for Medical Oncology Congress.
The survey of patients found that most don’t understand how immunotherapy works, and the survey of doctors found that many working outside of the cancer field are using information on survival that is wildly out of date.
When a patient is first told they have cancer, counseling is usually done by a surgeon or general medical doctor and not an oncologist, said Conleth Murphy, MD, of Bon Secours Hospital Cork, Ireland, and coauthor of the second study.
Noncancer doctors often grossly underestimate patients’ chances of survival, Dr. Murphy’s study found. This suggests that doctors who practice outside of cancer care may be working with the same information they learned in medical school, he said.
“These patients must be spared the traumatic effects of being handed a death sentence that no longer reflects the current reality,” Dr. Murphy said.
After receiving a diagnosis of cancer, “patients often immediately have pressing questions about what it means for their future,” he noted. A common question is: “How long do I have left?”
Nononcologists should refrain from answering patients’ questions with numbers, Dr. Murphy said.
Family doctors are likely to be influenced by the experience they have had with specific cancer patients in their practice, said Cyril Bonin, MD, a general practitioner in Usson-du-Poitou, France, who has 900 patients in his practice.
He sees about 10 patients with a new diagnosis of cancer each year. In addition, about 50 of his patients are in active treatment for cancer or have finished treatment and are considered cancer survivors.
“It is not entirely realistic for us to expect practitioners who deal with hundreds of different diseases to keep up with every facet of a rapidly changing oncology landscape,” said Marco Donia, MD, an expert in immunotherapy from the University of Copenhagen.
That landscape has changed dramatically in recent years, particularly since immunotherapy was added to the arsenal. Immunotherapy is a way to fine-tune your immune system to fight cancer.
For example, in the past, patients with metastatic melanoma would have an average survival of about 1 year. But now, some patients who have responded to immunotherapy are still alive 10 years later.
Findings from the patient survey
It is important that patients stay well informed because immunotherapy is a “complex treatment that is too often mistaken for a miracle cure,” said Paris Kosmidis, MD, the co-author of the patient survey.
“The more patients know about it, the better the communication with their medical team and thus the better their outcomes are likely to be,” said Dr. Kosmidis, who is co-founder and chief medical officer of CareAcross, an online service that provides personalized education for cancer patients
The survey was of 5,589 patients with cancer who were recruited from CareAcross clients from the United Kingdom, France, Italy, Spain, and Germany.
The survey asked them about how immunotherapy works, what it costs, and its side effects.
Almost half responded “not sure/do not know,” but about a third correctly answered that immunotherapy “activates the immune system to kill cancer cells.”
Similarly, more than half thought that immunotherapy started working right away, while only 20% correctly answered that it takes several weeks to become effective.
“This is important because patients need to start their therapy with realistic expectations, for example to avoid disappointment when their symptoms take some time to disappear,” Dr. Kosmidis said.
A small group of 24 patients with lung cancer who had been treated with immunotherapy got many correct answers, but they overestimated the intensity of side effects, compared with other therapies.
“Well-informed patients who know what to expect can do 90% of the job of preventing side effects from becoming severe by having them treated early,” said Dr. Donia, of the University of Copenhagen.
Most cancer patients were also unaware of the cost of immunotherapy, which can exceed $100,000 a year, Dr. Kosmidis said.
Results of the doctor survey
The other survey presented at the meeting looked at how much doctors know about survival for 12 of the most common cancers.
Dr. Murphy and colleagues asked 301 noncancer doctors and 46 cancer specialists to estimate the percentage of patients who could be expected to live for 5 years after diagnosis (a measure known as the 5-year survival rate).
Answers from the two groups were compared and graded according to cancer survival statistics from the National Cancer Registry of Ireland.
Both groups of doctors had a hard time estimating the survival of common cancers.
Nononcologists accurately predicted 5-year survival for just two of the cancer types, while the cancer specialists got it right for four cancer types.
However, the noncancer doctors had a more pessimistic outlook on cancer survival generally and severely underestimated the chances of survival in specific cancers, particularly stage IV breast cancer. The survival for this cancer has “evolved considerably over time and now reaches 40% in Ireland,” Dr. Murphy pointed out.
“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past,” Dr. Murphy said.
A version of this article first appeared on Medscape.com.
This is the main finding from two studies presented at the 2021 European Society for Medical Oncology Congress.
The survey of patients found that most don’t understand how immunotherapy works, and the survey of doctors found that many working outside of the cancer field are using information on survival that is wildly out of date.
When a patient is first told they have cancer, counseling is usually done by a surgeon or general medical doctor and not an oncologist, said Conleth Murphy, MD, of Bon Secours Hospital Cork, Ireland, and coauthor of the second study.
Noncancer doctors often grossly underestimate patients’ chances of survival, Dr. Murphy’s study found. This suggests that doctors who practice outside of cancer care may be working with the same information they learned in medical school, he said.
“These patients must be spared the traumatic effects of being handed a death sentence that no longer reflects the current reality,” Dr. Murphy said.
After receiving a diagnosis of cancer, “patients often immediately have pressing questions about what it means for their future,” he noted. A common question is: “How long do I have left?”
Nononcologists should refrain from answering patients’ questions with numbers, Dr. Murphy said.
Family doctors are likely to be influenced by the experience they have had with specific cancer patients in their practice, said Cyril Bonin, MD, a general practitioner in Usson-du-Poitou, France, who has 900 patients in his practice.
He sees about 10 patients with a new diagnosis of cancer each year. In addition, about 50 of his patients are in active treatment for cancer or have finished treatment and are considered cancer survivors.
“It is not entirely realistic for us to expect practitioners who deal with hundreds of different diseases to keep up with every facet of a rapidly changing oncology landscape,” said Marco Donia, MD, an expert in immunotherapy from the University of Copenhagen.
That landscape has changed dramatically in recent years, particularly since immunotherapy was added to the arsenal. Immunotherapy is a way to fine-tune your immune system to fight cancer.
For example, in the past, patients with metastatic melanoma would have an average survival of about 1 year. But now, some patients who have responded to immunotherapy are still alive 10 years later.
Findings from the patient survey
It is important that patients stay well informed because immunotherapy is a “complex treatment that is too often mistaken for a miracle cure,” said Paris Kosmidis, MD, the co-author of the patient survey.
“The more patients know about it, the better the communication with their medical team and thus the better their outcomes are likely to be,” said Dr. Kosmidis, who is co-founder and chief medical officer of CareAcross, an online service that provides personalized education for cancer patients
The survey was of 5,589 patients with cancer who were recruited from CareAcross clients from the United Kingdom, France, Italy, Spain, and Germany.
The survey asked them about how immunotherapy works, what it costs, and its side effects.
Almost half responded “not sure/do not know,” but about a third correctly answered that immunotherapy “activates the immune system to kill cancer cells.”
Similarly, more than half thought that immunotherapy started working right away, while only 20% correctly answered that it takes several weeks to become effective.
“This is important because patients need to start their therapy with realistic expectations, for example to avoid disappointment when their symptoms take some time to disappear,” Dr. Kosmidis said.
A small group of 24 patients with lung cancer who had been treated with immunotherapy got many correct answers, but they overestimated the intensity of side effects, compared with other therapies.
“Well-informed patients who know what to expect can do 90% of the job of preventing side effects from becoming severe by having them treated early,” said Dr. Donia, of the University of Copenhagen.
Most cancer patients were also unaware of the cost of immunotherapy, which can exceed $100,000 a year, Dr. Kosmidis said.
Results of the doctor survey
The other survey presented at the meeting looked at how much doctors know about survival for 12 of the most common cancers.
Dr. Murphy and colleagues asked 301 noncancer doctors and 46 cancer specialists to estimate the percentage of patients who could be expected to live for 5 years after diagnosis (a measure known as the 5-year survival rate).
Answers from the two groups were compared and graded according to cancer survival statistics from the National Cancer Registry of Ireland.
Both groups of doctors had a hard time estimating the survival of common cancers.
Nononcologists accurately predicted 5-year survival for just two of the cancer types, while the cancer specialists got it right for four cancer types.
However, the noncancer doctors had a more pessimistic outlook on cancer survival generally and severely underestimated the chances of survival in specific cancers, particularly stage IV breast cancer. The survival for this cancer has “evolved considerably over time and now reaches 40% in Ireland,” Dr. Murphy pointed out.
“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past,” Dr. Murphy said.
A version of this article first appeared on Medscape.com.
This is the main finding from two studies presented at the 2021 European Society for Medical Oncology Congress.
The survey of patients found that most don’t understand how immunotherapy works, and the survey of doctors found that many working outside of the cancer field are using information on survival that is wildly out of date.
When a patient is first told they have cancer, counseling is usually done by a surgeon or general medical doctor and not an oncologist, said Conleth Murphy, MD, of Bon Secours Hospital Cork, Ireland, and coauthor of the second study.
Noncancer doctors often grossly underestimate patients’ chances of survival, Dr. Murphy’s study found. This suggests that doctors who practice outside of cancer care may be working with the same information they learned in medical school, he said.
“These patients must be spared the traumatic effects of being handed a death sentence that no longer reflects the current reality,” Dr. Murphy said.
After receiving a diagnosis of cancer, “patients often immediately have pressing questions about what it means for their future,” he noted. A common question is: “How long do I have left?”
Nononcologists should refrain from answering patients’ questions with numbers, Dr. Murphy said.
Family doctors are likely to be influenced by the experience they have had with specific cancer patients in their practice, said Cyril Bonin, MD, a general practitioner in Usson-du-Poitou, France, who has 900 patients in his practice.
He sees about 10 patients with a new diagnosis of cancer each year. In addition, about 50 of his patients are in active treatment for cancer or have finished treatment and are considered cancer survivors.
“It is not entirely realistic for us to expect practitioners who deal with hundreds of different diseases to keep up with every facet of a rapidly changing oncology landscape,” said Marco Donia, MD, an expert in immunotherapy from the University of Copenhagen.
That landscape has changed dramatically in recent years, particularly since immunotherapy was added to the arsenal. Immunotherapy is a way to fine-tune your immune system to fight cancer.
For example, in the past, patients with metastatic melanoma would have an average survival of about 1 year. But now, some patients who have responded to immunotherapy are still alive 10 years later.
Findings from the patient survey
It is important that patients stay well informed because immunotherapy is a “complex treatment that is too often mistaken for a miracle cure,” said Paris Kosmidis, MD, the co-author of the patient survey.
“The more patients know about it, the better the communication with their medical team and thus the better their outcomes are likely to be,” said Dr. Kosmidis, who is co-founder and chief medical officer of CareAcross, an online service that provides personalized education for cancer patients
The survey was of 5,589 patients with cancer who were recruited from CareAcross clients from the United Kingdom, France, Italy, Spain, and Germany.
The survey asked them about how immunotherapy works, what it costs, and its side effects.
Almost half responded “not sure/do not know,” but about a third correctly answered that immunotherapy “activates the immune system to kill cancer cells.”
Similarly, more than half thought that immunotherapy started working right away, while only 20% correctly answered that it takes several weeks to become effective.
“This is important because patients need to start their therapy with realistic expectations, for example to avoid disappointment when their symptoms take some time to disappear,” Dr. Kosmidis said.
A small group of 24 patients with lung cancer who had been treated with immunotherapy got many correct answers, but they overestimated the intensity of side effects, compared with other therapies.
“Well-informed patients who know what to expect can do 90% of the job of preventing side effects from becoming severe by having them treated early,” said Dr. Donia, of the University of Copenhagen.
Most cancer patients were also unaware of the cost of immunotherapy, which can exceed $100,000 a year, Dr. Kosmidis said.
Results of the doctor survey
The other survey presented at the meeting looked at how much doctors know about survival for 12 of the most common cancers.
Dr. Murphy and colleagues asked 301 noncancer doctors and 46 cancer specialists to estimate the percentage of patients who could be expected to live for 5 years after diagnosis (a measure known as the 5-year survival rate).
Answers from the two groups were compared and graded according to cancer survival statistics from the National Cancer Registry of Ireland.
Both groups of doctors had a hard time estimating the survival of common cancers.
Nononcologists accurately predicted 5-year survival for just two of the cancer types, while the cancer specialists got it right for four cancer types.
However, the noncancer doctors had a more pessimistic outlook on cancer survival generally and severely underestimated the chances of survival in specific cancers, particularly stage IV breast cancer. The survival for this cancer has “evolved considerably over time and now reaches 40% in Ireland,” Dr. Murphy pointed out.
“These results are in line with what we had expected because most physicians’ knowledge of oncology dates back to whatever education they received during their years of training, so their perceptions of cancer prognosis are likely to lag behind the major survival gains achieved in the recent past,” Dr. Murphy said.
A version of this article first appeared on Medscape.com.
‘Unprecedented’ 3-year sustained survival with lung cancer combo treatment
The durable overall survival (OS) benefit and the well-tolerated safety profile of the durvalumab with EP therapy further establishes the combination as the standard of care for the first-line treatment of ES-SCLC, Luis Paz-Ares, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 18 (abstract LBA61).
At 3 years, there is more than three times the survival in patients with durvalumab and EP versus EP, and at the same time, the adverse-event profile continues to be favorable,” said Dr. Paz-Ares of Universidad Complutense & Ciberonc, Madrid.
This is the longest follow-up reported to date for a phase 3 trial of a programmed death–ligand 1 inhibitor and EP in this setting, he said.
The CASPIAN trial included 805 treatment-naive patients with ES-SCLC who were randomized 1:1:1 to receive 1,500 mg of durvalumab with EP every 3 weeks, 1,500 mg of durvalumab at 75 mg of tremelimumab and EP every 3 weeks, or EP alone. Patients in the durvalumab arms received four cycles of treatment followed by maintenance durvalumab, and those in the EP-only arm received up to six cycles of EP.
Primary outcomes data from the trial showed a significant overall survival benefit with durvalumab and EP versus EP alone (hazard ratio, 0.73), as did a subsequent analysis after a median follow-up of 25.1 mo (HR, 0.75).
Durvalumab with tremelimumab and EP numerically improved overall survival versus EP (HR, 0.82), but did not reach statistical significance.
At median follow up of 39.4 months, the durvalumab and EP combination showed sustained improvement in overall survival versus EP alone (HR, 0.71).
Median overall survival was 12.9 versus 10.5 months. OS was 22.9% versus 13.9% at 24 months, and 17.6% versus 5.8% at 36 months with durvalumab with EP versus EP, respectively, Dr. Paz-Ares said.
Durvalumab plus tremelimumab plus EP continued to numerically improve overall survival, compared with EP alone (HR, 0.81); median OS in that arm was 10.4 months, and 15.3% of patients were alive at 36 months, he noted.
Serious adverse events occurred in 32.5%, 47.4%, and 36.5% of patients in the durvalumab with EP, durvalumab plus tremelimumab plus EP, and EP arms respectively, and adverse events leading to death occurred in 5.3%, 10.9%, and 6.0%, respectively.
The findings are “really encouraging and unprecedented, frankly,” said session chair Alfredo Addeo, MD, of University Hospital, Geneva.
“They are setting the bar for competitors,” he said, referencing the IMpower 133 trial looking at atezolizumab with chemotherapy in ES-SCLC.
The CASPIAN study was funded by AstraZeneca. Dr. Paz-Ares reported relationships with multiple pharmaceutical companies.
The durable overall survival (OS) benefit and the well-tolerated safety profile of the durvalumab with EP therapy further establishes the combination as the standard of care for the first-line treatment of ES-SCLC, Luis Paz-Ares, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 18 (abstract LBA61).
At 3 years, there is more than three times the survival in patients with durvalumab and EP versus EP, and at the same time, the adverse-event profile continues to be favorable,” said Dr. Paz-Ares of Universidad Complutense & Ciberonc, Madrid.
This is the longest follow-up reported to date for a phase 3 trial of a programmed death–ligand 1 inhibitor and EP in this setting, he said.
The CASPIAN trial included 805 treatment-naive patients with ES-SCLC who were randomized 1:1:1 to receive 1,500 mg of durvalumab with EP every 3 weeks, 1,500 mg of durvalumab at 75 mg of tremelimumab and EP every 3 weeks, or EP alone. Patients in the durvalumab arms received four cycles of treatment followed by maintenance durvalumab, and those in the EP-only arm received up to six cycles of EP.
Primary outcomes data from the trial showed a significant overall survival benefit with durvalumab and EP versus EP alone (hazard ratio, 0.73), as did a subsequent analysis after a median follow-up of 25.1 mo (HR, 0.75).
Durvalumab with tremelimumab and EP numerically improved overall survival versus EP (HR, 0.82), but did not reach statistical significance.
At median follow up of 39.4 months, the durvalumab and EP combination showed sustained improvement in overall survival versus EP alone (HR, 0.71).
Median overall survival was 12.9 versus 10.5 months. OS was 22.9% versus 13.9% at 24 months, and 17.6% versus 5.8% at 36 months with durvalumab with EP versus EP, respectively, Dr. Paz-Ares said.
Durvalumab plus tremelimumab plus EP continued to numerically improve overall survival, compared with EP alone (HR, 0.81); median OS in that arm was 10.4 months, and 15.3% of patients were alive at 36 months, he noted.
Serious adverse events occurred in 32.5%, 47.4%, and 36.5% of patients in the durvalumab with EP, durvalumab plus tremelimumab plus EP, and EP arms respectively, and adverse events leading to death occurred in 5.3%, 10.9%, and 6.0%, respectively.
The findings are “really encouraging and unprecedented, frankly,” said session chair Alfredo Addeo, MD, of University Hospital, Geneva.
“They are setting the bar for competitors,” he said, referencing the IMpower 133 trial looking at atezolizumab with chemotherapy in ES-SCLC.
The CASPIAN study was funded by AstraZeneca. Dr. Paz-Ares reported relationships with multiple pharmaceutical companies.
The durable overall survival (OS) benefit and the well-tolerated safety profile of the durvalumab with EP therapy further establishes the combination as the standard of care for the first-line treatment of ES-SCLC, Luis Paz-Ares, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 18 (abstract LBA61).
At 3 years, there is more than three times the survival in patients with durvalumab and EP versus EP, and at the same time, the adverse-event profile continues to be favorable,” said Dr. Paz-Ares of Universidad Complutense & Ciberonc, Madrid.
This is the longest follow-up reported to date for a phase 3 trial of a programmed death–ligand 1 inhibitor and EP in this setting, he said.
The CASPIAN trial included 805 treatment-naive patients with ES-SCLC who were randomized 1:1:1 to receive 1,500 mg of durvalumab with EP every 3 weeks, 1,500 mg of durvalumab at 75 mg of tremelimumab and EP every 3 weeks, or EP alone. Patients in the durvalumab arms received four cycles of treatment followed by maintenance durvalumab, and those in the EP-only arm received up to six cycles of EP.
Primary outcomes data from the trial showed a significant overall survival benefit with durvalumab and EP versus EP alone (hazard ratio, 0.73), as did a subsequent analysis after a median follow-up of 25.1 mo (HR, 0.75).
Durvalumab with tremelimumab and EP numerically improved overall survival versus EP (HR, 0.82), but did not reach statistical significance.
At median follow up of 39.4 months, the durvalumab and EP combination showed sustained improvement in overall survival versus EP alone (HR, 0.71).
Median overall survival was 12.9 versus 10.5 months. OS was 22.9% versus 13.9% at 24 months, and 17.6% versus 5.8% at 36 months with durvalumab with EP versus EP, respectively, Dr. Paz-Ares said.
Durvalumab plus tremelimumab plus EP continued to numerically improve overall survival, compared with EP alone (HR, 0.81); median OS in that arm was 10.4 months, and 15.3% of patients were alive at 36 months, he noted.
Serious adverse events occurred in 32.5%, 47.4%, and 36.5% of patients in the durvalumab with EP, durvalumab plus tremelimumab plus EP, and EP arms respectively, and adverse events leading to death occurred in 5.3%, 10.9%, and 6.0%, respectively.
The findings are “really encouraging and unprecedented, frankly,” said session chair Alfredo Addeo, MD, of University Hospital, Geneva.
“They are setting the bar for competitors,” he said, referencing the IMpower 133 trial looking at atezolizumab with chemotherapy in ES-SCLC.
The CASPIAN study was funded by AstraZeneca. Dr. Paz-Ares reported relationships with multiple pharmaceutical companies.
FROM ESMO 2021
Use of Biomarkers to Optimize Treatment of NSCLC
Benjamin Cooper, MD, Director of Proton Therapy at NYU Langone Health, discusses how physicians who treat patients with non-small cell lung cancer (NSCLC) can use genetic profiling results to select effective therapy. Although the current list of therapies is not applicable to all genetic mutations, there are approved treatments for several biomarkers and agents targeting other biomarkers are in clinical trials.
Dr. Cooper explains that biomarkers in NSCLC either boost the immune system’s capability to destroy oncogenes or they block driver and escape mutations that advance disease.
Immunotherapies that target either PD-1 or PD-L1 are now mainstays of NSCLC treatment. To gauge whether these therapies have potential effectiveness for a given patient, oncologists test for the presence of PD-L1 in the tumor. Higher expression of PD-L1 indicates stronger potential response to therapy.
Dr. Cooper then turns to a discussion of oncogenic driver mutations, focusing on EGFR, ALK, ROS1, BRAF, NTRK, RET, MET, KRAS, and HER2. Although there are hundreds of oncogenic driver mutations, not all are currently actionable. Effective therapy options have been available for EGFR, ALK, and BRAF for more than a decade, and treatments for other drivers such as NTRK, MET, KRAS, and HER2 have shown promising results in recent trials.
--
Benjamin Cooper, MD is an Assistant Professor, Department of Radiation Oncology, Director, Proton Therapy Services, NYU Grossman School of Medicine,
New York, New York
Benjamin Cooper, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca.
Benjamin Cooper, MD, Director of Proton Therapy at NYU Langone Health, discusses how physicians who treat patients with non-small cell lung cancer (NSCLC) can use genetic profiling results to select effective therapy. Although the current list of therapies is not applicable to all genetic mutations, there are approved treatments for several biomarkers and agents targeting other biomarkers are in clinical trials.
Dr. Cooper explains that biomarkers in NSCLC either boost the immune system’s capability to destroy oncogenes or they block driver and escape mutations that advance disease.
Immunotherapies that target either PD-1 or PD-L1 are now mainstays of NSCLC treatment. To gauge whether these therapies have potential effectiveness for a given patient, oncologists test for the presence of PD-L1 in the tumor. Higher expression of PD-L1 indicates stronger potential response to therapy.
Dr. Cooper then turns to a discussion of oncogenic driver mutations, focusing on EGFR, ALK, ROS1, BRAF, NTRK, RET, MET, KRAS, and HER2. Although there are hundreds of oncogenic driver mutations, not all are currently actionable. Effective therapy options have been available for EGFR, ALK, and BRAF for more than a decade, and treatments for other drivers such as NTRK, MET, KRAS, and HER2 have shown promising results in recent trials.
--
Benjamin Cooper, MD is an Assistant Professor, Department of Radiation Oncology, Director, Proton Therapy Services, NYU Grossman School of Medicine,
New York, New York
Benjamin Cooper, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca.
Benjamin Cooper, MD, Director of Proton Therapy at NYU Langone Health, discusses how physicians who treat patients with non-small cell lung cancer (NSCLC) can use genetic profiling results to select effective therapy. Although the current list of therapies is not applicable to all genetic mutations, there are approved treatments for several biomarkers and agents targeting other biomarkers are in clinical trials.
Dr. Cooper explains that biomarkers in NSCLC either boost the immune system’s capability to destroy oncogenes or they block driver and escape mutations that advance disease.
Immunotherapies that target either PD-1 or PD-L1 are now mainstays of NSCLC treatment. To gauge whether these therapies have potential effectiveness for a given patient, oncologists test for the presence of PD-L1 in the tumor. Higher expression of PD-L1 indicates stronger potential response to therapy.
Dr. Cooper then turns to a discussion of oncogenic driver mutations, focusing on EGFR, ALK, ROS1, BRAF, NTRK, RET, MET, KRAS, and HER2. Although there are hundreds of oncogenic driver mutations, not all are currently actionable. Effective therapy options have been available for EGFR, ALK, and BRAF for more than a decade, and treatments for other drivers such as NTRK, MET, KRAS, and HER2 have shown promising results in recent trials.
--
Benjamin Cooper, MD is an Assistant Professor, Department of Radiation Oncology, Director, Proton Therapy Services, NYU Grossman School of Medicine,
New York, New York
Benjamin Cooper, MD, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca.
Response to preop immunotherapy predicts survival in early NSCLC
Although major pathological response after neoadjuvant cisplatin-based chemotherapy has been shown to predict survival in patients with early-stage NSCLC, this is the first time a similar association has been demonstrated with neoadjuvant immune checkpoint inhibition, Marie Wislez, MD, PhD, a researcher at Hopital Cochin, Paris, reported at the 2021 European Society of Medical Oncology Congress.
Primary outcomes of the multicenter trial showed 12- and 18-month OS of 89.1%, and 12- and 18-month DFS of 78.3% and 73.7%, respectively, in 46 patients treated with preoperative durvalumab. Median OS and DFS were not reached.
Major pathological response was observed in eight patients (18.6%), with three patients experiencing complete pathological response. No deaths or recurrences were observed in patients in this group. A significant association was observed between major pathological response and DFS. However, the study was stopped early because of excessive 90-day postoperative mortality, which the authors said were most likely related to comorbidities.
The current post hoc analysis of data from the study showed poorer overall survival and disease-free survival with increasing percentage of residual viable tumor (RVT) cells on multivariate prognostic analysis (hazard ratio, 1.05 and 1.06; P = .04 and .02, respectively), Dr. Wislez said in her presentation made on Sept. 18 (abstract 1151MO).
“For each 10% increase of RVT, you have an increased risk of death of 64% and increased risk of recurrence of 71%,” she said.
Study subjects, who were enrolled between April 2017 and August 2019, had a median age of 61 years, 67.4% were men, 98% were smokers or former smokes, and all had Eastern Cooperative Oncology Group performance status scores of 0-1. The median percentage of RVT cells was 36.11.
Of the 50 patients enrolled, 46 were eligible for and received durvalumab and 43 underwent surgery. Those with stages IB and 4 cm or greater tumor size to stage IIIA non-N2 NSCLC received three cycles of durvalumab before surgery. Durvalumab was given intravenously at a dose of 750 mg on days 1, 15, and 29, and surgery was performed 2-14 days after the last infusion.
Tissue specimens from patients who underwent neoadjuvant durvalumab and complete surgical resection were retrospectively evaluated by two pathologists blinded to patient outcomes, Dr. Wislez noted.
Session chair Michael Thomas, MD, of Thoraxklinik-Heidelberg at Heidelberg (Germany) University Hospital, described the study as “hypotheses generating,” and noted that it suggests incremental step-wise assessment of pathological response could be an additional tool for subgrouping of patients in upcoming trials.
Indeed, this novel finding suggests that the extent of pathological response could be considered as a surrogate marker for neoadjuvant treatment trials, although the use of a continuous variable would be challenging in the trial setting, Dr. Wislez agreed.
“But it’s a demonstration that [with] immunotherapy monotherapy ... the extent of pathological response is associated with overall survival,” she said.
This study was funded by AstraZeneca. Dr. Wislez reported honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche, Novartis, Merck, and MSD.
Although major pathological response after neoadjuvant cisplatin-based chemotherapy has been shown to predict survival in patients with early-stage NSCLC, this is the first time a similar association has been demonstrated with neoadjuvant immune checkpoint inhibition, Marie Wislez, MD, PhD, a researcher at Hopital Cochin, Paris, reported at the 2021 European Society of Medical Oncology Congress.
Primary outcomes of the multicenter trial showed 12- and 18-month OS of 89.1%, and 12- and 18-month DFS of 78.3% and 73.7%, respectively, in 46 patients treated with preoperative durvalumab. Median OS and DFS were not reached.
Major pathological response was observed in eight patients (18.6%), with three patients experiencing complete pathological response. No deaths or recurrences were observed in patients in this group. A significant association was observed between major pathological response and DFS. However, the study was stopped early because of excessive 90-day postoperative mortality, which the authors said were most likely related to comorbidities.
The current post hoc analysis of data from the study showed poorer overall survival and disease-free survival with increasing percentage of residual viable tumor (RVT) cells on multivariate prognostic analysis (hazard ratio, 1.05 and 1.06; P = .04 and .02, respectively), Dr. Wislez said in her presentation made on Sept. 18 (abstract 1151MO).
“For each 10% increase of RVT, you have an increased risk of death of 64% and increased risk of recurrence of 71%,” she said.
Study subjects, who were enrolled between April 2017 and August 2019, had a median age of 61 years, 67.4% were men, 98% were smokers or former smokes, and all had Eastern Cooperative Oncology Group performance status scores of 0-1. The median percentage of RVT cells was 36.11.
Of the 50 patients enrolled, 46 were eligible for and received durvalumab and 43 underwent surgery. Those with stages IB and 4 cm or greater tumor size to stage IIIA non-N2 NSCLC received three cycles of durvalumab before surgery. Durvalumab was given intravenously at a dose of 750 mg on days 1, 15, and 29, and surgery was performed 2-14 days after the last infusion.
Tissue specimens from patients who underwent neoadjuvant durvalumab and complete surgical resection were retrospectively evaluated by two pathologists blinded to patient outcomes, Dr. Wislez noted.
Session chair Michael Thomas, MD, of Thoraxklinik-Heidelberg at Heidelberg (Germany) University Hospital, described the study as “hypotheses generating,” and noted that it suggests incremental step-wise assessment of pathological response could be an additional tool for subgrouping of patients in upcoming trials.
Indeed, this novel finding suggests that the extent of pathological response could be considered as a surrogate marker for neoadjuvant treatment trials, although the use of a continuous variable would be challenging in the trial setting, Dr. Wislez agreed.
“But it’s a demonstration that [with] immunotherapy monotherapy ... the extent of pathological response is associated with overall survival,” she said.
This study was funded by AstraZeneca. Dr. Wislez reported honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche, Novartis, Merck, and MSD.
Although major pathological response after neoadjuvant cisplatin-based chemotherapy has been shown to predict survival in patients with early-stage NSCLC, this is the first time a similar association has been demonstrated with neoadjuvant immune checkpoint inhibition, Marie Wislez, MD, PhD, a researcher at Hopital Cochin, Paris, reported at the 2021 European Society of Medical Oncology Congress.
Primary outcomes of the multicenter trial showed 12- and 18-month OS of 89.1%, and 12- and 18-month DFS of 78.3% and 73.7%, respectively, in 46 patients treated with preoperative durvalumab. Median OS and DFS were not reached.
Major pathological response was observed in eight patients (18.6%), with three patients experiencing complete pathological response. No deaths or recurrences were observed in patients in this group. A significant association was observed between major pathological response and DFS. However, the study was stopped early because of excessive 90-day postoperative mortality, which the authors said were most likely related to comorbidities.
The current post hoc analysis of data from the study showed poorer overall survival and disease-free survival with increasing percentage of residual viable tumor (RVT) cells on multivariate prognostic analysis (hazard ratio, 1.05 and 1.06; P = .04 and .02, respectively), Dr. Wislez said in her presentation made on Sept. 18 (abstract 1151MO).
“For each 10% increase of RVT, you have an increased risk of death of 64% and increased risk of recurrence of 71%,” she said.
Study subjects, who were enrolled between April 2017 and August 2019, had a median age of 61 years, 67.4% were men, 98% were smokers or former smokes, and all had Eastern Cooperative Oncology Group performance status scores of 0-1. The median percentage of RVT cells was 36.11.
Of the 50 patients enrolled, 46 were eligible for and received durvalumab and 43 underwent surgery. Those with stages IB and 4 cm or greater tumor size to stage IIIA non-N2 NSCLC received three cycles of durvalumab before surgery. Durvalumab was given intravenously at a dose of 750 mg on days 1, 15, and 29, and surgery was performed 2-14 days after the last infusion.
Tissue specimens from patients who underwent neoadjuvant durvalumab and complete surgical resection were retrospectively evaluated by two pathologists blinded to patient outcomes, Dr. Wislez noted.
Session chair Michael Thomas, MD, of Thoraxklinik-Heidelberg at Heidelberg (Germany) University Hospital, described the study as “hypotheses generating,” and noted that it suggests incremental step-wise assessment of pathological response could be an additional tool for subgrouping of patients in upcoming trials.
Indeed, this novel finding suggests that the extent of pathological response could be considered as a surrogate marker for neoadjuvant treatment trials, although the use of a continuous variable would be challenging in the trial setting, Dr. Wislez agreed.
“But it’s a demonstration that [with] immunotherapy monotherapy ... the extent of pathological response is associated with overall survival,” she said.
This study was funded by AstraZeneca. Dr. Wislez reported honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche, Novartis, Merck, and MSD.
FROM ESMO 2021
Studies confirm survival benefit with postchemoradiotherapy consolidation in NSCLC
Checkpoint inhibition for consolidation after chemoradiotherapy (CRT) showed promising survival benefit in patients with unresectable stage III non–small cell lung cancer (NSCLC) in two recent studies, including one looking at the investigational agent sugemalimab and one assessing durvalumab in a real-world setting.
Statistically significant and clinically meaningful improvement in progression-free survival (PFS) was observed with sugemalimab versus placebo in the randomized, phase 3 GEMSTONE-301 study, and consolidation durvalumab showed effectiveness in a real-world cohort in the PACIFIC-R study.
Findings from both studies were presented at the 2021 European Society for Medical Oncology Congress.
GEMSTONE-301
Median progression-free survival among 381 patients randomized 2:1 to receive 1,200 mg of sugemalimab or placebo every 3 weeks after either concurrent or sequential chemoradiotherapy was 9.0 versus 5.8 months, in the treatment arms, respectively (hazard ratio, 0.64) (Abstract LBA43), reported Yi-Long Wu, MD, of Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.
Patients were recruited from 50 sites, and one-third had received sequential CRT. Progression-free survival was assessed at median follow up of 14 months.
“The 12- and 18-month PFS rates were 45% vs. 26% and 39% vs. 23%, respectively,” Dr. Wu said.
Of note, the PFS benefit was observed both for patients who underwent sequential CRT (median PFS, 8.1 vs. 4.1 months with sugemalimab vs. placebo; hazard ratio, 0.59) and for those who received concurrent CRT (median PFS, 10.5 vs. 6.4 months; HR, 0.66).
Overall survival (OS) data were not mature at the time of the presentation, but a trend favoring sugemalimab was observed (HR, 0.44) he noted.
Sugemalimab, an investigational anti–programmed death-ligand 1 (PD-L1 )monoclonal antibody, was well tolerated; grade 3 or higher treatment-emergent adverse events (AEs) occurred in 24.3% of patients in the sugemalimab group and in 23.8% in the placebo group.
Concurrent chemoradiotherapy followed by immunotherapy is the standard of care for patients with unresectable stage III NSCLC, but nearly half undergo sequential CRT because they can’t tolerate concurrent treatment, Dr. Wu explained, describing the rationale for the study – the first phase 3 trial looking at both concurrent and sequential CRT in this patient population.
The results provide evidence for sugemalimab as a consolidation treatment for those who did not progress following either approach to CRT, he concluded.
PACIFIC-R study
The large, international, observational PACIFIC-R study also looked at consolidation in a real-world setting, and confirmed a PFS benefit with durvalumab in stage III NSCLC patients who had completed concurrent or sequential platinum-based CRT within the previous 12 weeks without evidence of disease progression (Abstract 1171MO).
“The median real-world PFS in this cohort was 21.7 months, which is higher than that in the durvalumab arm in the PACIFIC trial, which was 16.9 months,” reported Nicolas Girard, MD, a professor at Institut Curie, Paris.
The PACIFIC trial set the standard for durvalumab-based consolidation after CRT, and ongoing survival benefit was confirmed by 5-year follow-up data, he noted.
The PACIFIC-R trial included 1,399 patients from 11 countries who were treated as part of an expanded-access program following the PACIFIC trial.
Median time to durvalumab initiation after the end of radiotherapy in the cohort was 56 days. Overall median durvalumab treatment duration was 11 months, and the median number of infusions was 22, Dr. Girard said.
Pneumonitis was the most common adverse event leading to discontinuation: 214 (18.5%) patients experienced any-grade pneumonitis and/or interstitial lung disease, and 9.5 discontinued the study as a result. Most cases were mild or moderate, he said.
Subgroup analyses showed that real-world PFS was higher among patients with stage IIIa disease and those with PD-L1–positive tumors, those with nonsquamous disease histology, and those who received concurrent CRT.
“For example, in those with stage IIIa disease, the median real-world PFS was 23.7 months versus 19.2 months in patients with stage IIIb and c disease,” he said.
“PACIFIC-R demonstrated the efficacy of durvalumab consolidation in patients with unresectable stage III non–small cell lung cancer after completion of chemoradiotherapy,” said Dr. Girard. “The effectiveness of durvalumab was consistent among key subgroups, as was safety, when comparing the data with that of PACIFIC.
“The future read-outs of OS will further provide insight into the effectiveness of this regimen.”
Session chair Lizza E. Hendriks, MD, PhD, of Maastricht (the Netherlands) University, applauded the inclusion of patients undergoing sequential CRT in the GEMSTONE-301 and PACIFIC-R studies, noting that it is “very important to have data in sequential radiochemotherapy populations” given the substantial number of patients who require a sequential approach because of poor performance status, difficulty tolerating concurrent CRT, or logistical reasons, such as an inability to travel to receive concurrent CRT.
The GEMSTONE-301 study was funded by CStone Pharmaceuticals. Dr. Wu reported having no disclosures. The PACIFIC-R study was funded by AstraZeneca. Dr. Girard reported financial relationships with AstraZeneca, Bristol Myers Squibb, and Merck Sharp & Dohme. Dr. Hendriks reported financial relationships with numerous companies.
Checkpoint inhibition for consolidation after chemoradiotherapy (CRT) showed promising survival benefit in patients with unresectable stage III non–small cell lung cancer (NSCLC) in two recent studies, including one looking at the investigational agent sugemalimab and one assessing durvalumab in a real-world setting.
Statistically significant and clinically meaningful improvement in progression-free survival (PFS) was observed with sugemalimab versus placebo in the randomized, phase 3 GEMSTONE-301 study, and consolidation durvalumab showed effectiveness in a real-world cohort in the PACIFIC-R study.
Findings from both studies were presented at the 2021 European Society for Medical Oncology Congress.
GEMSTONE-301
Median progression-free survival among 381 patients randomized 2:1 to receive 1,200 mg of sugemalimab or placebo every 3 weeks after either concurrent or sequential chemoradiotherapy was 9.0 versus 5.8 months, in the treatment arms, respectively (hazard ratio, 0.64) (Abstract LBA43), reported Yi-Long Wu, MD, of Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.
Patients were recruited from 50 sites, and one-third had received sequential CRT. Progression-free survival was assessed at median follow up of 14 months.
“The 12- and 18-month PFS rates were 45% vs. 26% and 39% vs. 23%, respectively,” Dr. Wu said.
Of note, the PFS benefit was observed both for patients who underwent sequential CRT (median PFS, 8.1 vs. 4.1 months with sugemalimab vs. placebo; hazard ratio, 0.59) and for those who received concurrent CRT (median PFS, 10.5 vs. 6.4 months; HR, 0.66).
Overall survival (OS) data were not mature at the time of the presentation, but a trend favoring sugemalimab was observed (HR, 0.44) he noted.
Sugemalimab, an investigational anti–programmed death-ligand 1 (PD-L1 )monoclonal antibody, was well tolerated; grade 3 or higher treatment-emergent adverse events (AEs) occurred in 24.3% of patients in the sugemalimab group and in 23.8% in the placebo group.
Concurrent chemoradiotherapy followed by immunotherapy is the standard of care for patients with unresectable stage III NSCLC, but nearly half undergo sequential CRT because they can’t tolerate concurrent treatment, Dr. Wu explained, describing the rationale for the study – the first phase 3 trial looking at both concurrent and sequential CRT in this patient population.
The results provide evidence for sugemalimab as a consolidation treatment for those who did not progress following either approach to CRT, he concluded.
PACIFIC-R study
The large, international, observational PACIFIC-R study also looked at consolidation in a real-world setting, and confirmed a PFS benefit with durvalumab in stage III NSCLC patients who had completed concurrent or sequential platinum-based CRT within the previous 12 weeks without evidence of disease progression (Abstract 1171MO).
“The median real-world PFS in this cohort was 21.7 months, which is higher than that in the durvalumab arm in the PACIFIC trial, which was 16.9 months,” reported Nicolas Girard, MD, a professor at Institut Curie, Paris.
The PACIFIC trial set the standard for durvalumab-based consolidation after CRT, and ongoing survival benefit was confirmed by 5-year follow-up data, he noted.
The PACIFIC-R trial included 1,399 patients from 11 countries who were treated as part of an expanded-access program following the PACIFIC trial.
Median time to durvalumab initiation after the end of radiotherapy in the cohort was 56 days. Overall median durvalumab treatment duration was 11 months, and the median number of infusions was 22, Dr. Girard said.
Pneumonitis was the most common adverse event leading to discontinuation: 214 (18.5%) patients experienced any-grade pneumonitis and/or interstitial lung disease, and 9.5 discontinued the study as a result. Most cases were mild or moderate, he said.
Subgroup analyses showed that real-world PFS was higher among patients with stage IIIa disease and those with PD-L1–positive tumors, those with nonsquamous disease histology, and those who received concurrent CRT.
“For example, in those with stage IIIa disease, the median real-world PFS was 23.7 months versus 19.2 months in patients with stage IIIb and c disease,” he said.
“PACIFIC-R demonstrated the efficacy of durvalumab consolidation in patients with unresectable stage III non–small cell lung cancer after completion of chemoradiotherapy,” said Dr. Girard. “The effectiveness of durvalumab was consistent among key subgroups, as was safety, when comparing the data with that of PACIFIC.
“The future read-outs of OS will further provide insight into the effectiveness of this regimen.”
Session chair Lizza E. Hendriks, MD, PhD, of Maastricht (the Netherlands) University, applauded the inclusion of patients undergoing sequential CRT in the GEMSTONE-301 and PACIFIC-R studies, noting that it is “very important to have data in sequential radiochemotherapy populations” given the substantial number of patients who require a sequential approach because of poor performance status, difficulty tolerating concurrent CRT, or logistical reasons, such as an inability to travel to receive concurrent CRT.
The GEMSTONE-301 study was funded by CStone Pharmaceuticals. Dr. Wu reported having no disclosures. The PACIFIC-R study was funded by AstraZeneca. Dr. Girard reported financial relationships with AstraZeneca, Bristol Myers Squibb, and Merck Sharp & Dohme. Dr. Hendriks reported financial relationships with numerous companies.
Checkpoint inhibition for consolidation after chemoradiotherapy (CRT) showed promising survival benefit in patients with unresectable stage III non–small cell lung cancer (NSCLC) in two recent studies, including one looking at the investigational agent sugemalimab and one assessing durvalumab in a real-world setting.
Statistically significant and clinically meaningful improvement in progression-free survival (PFS) was observed with sugemalimab versus placebo in the randomized, phase 3 GEMSTONE-301 study, and consolidation durvalumab showed effectiveness in a real-world cohort in the PACIFIC-R study.
Findings from both studies were presented at the 2021 European Society for Medical Oncology Congress.
GEMSTONE-301
Median progression-free survival among 381 patients randomized 2:1 to receive 1,200 mg of sugemalimab or placebo every 3 weeks after either concurrent or sequential chemoradiotherapy was 9.0 versus 5.8 months, in the treatment arms, respectively (hazard ratio, 0.64) (Abstract LBA43), reported Yi-Long Wu, MD, of Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.
Patients were recruited from 50 sites, and one-third had received sequential CRT. Progression-free survival was assessed at median follow up of 14 months.
“The 12- and 18-month PFS rates were 45% vs. 26% and 39% vs. 23%, respectively,” Dr. Wu said.
Of note, the PFS benefit was observed both for patients who underwent sequential CRT (median PFS, 8.1 vs. 4.1 months with sugemalimab vs. placebo; hazard ratio, 0.59) and for those who received concurrent CRT (median PFS, 10.5 vs. 6.4 months; HR, 0.66).
Overall survival (OS) data were not mature at the time of the presentation, but a trend favoring sugemalimab was observed (HR, 0.44) he noted.
Sugemalimab, an investigational anti–programmed death-ligand 1 (PD-L1 )monoclonal antibody, was well tolerated; grade 3 or higher treatment-emergent adverse events (AEs) occurred in 24.3% of patients in the sugemalimab group and in 23.8% in the placebo group.
Concurrent chemoradiotherapy followed by immunotherapy is the standard of care for patients with unresectable stage III NSCLC, but nearly half undergo sequential CRT because they can’t tolerate concurrent treatment, Dr. Wu explained, describing the rationale for the study – the first phase 3 trial looking at both concurrent and sequential CRT in this patient population.
The results provide evidence for sugemalimab as a consolidation treatment for those who did not progress following either approach to CRT, he concluded.
PACIFIC-R study
The large, international, observational PACIFIC-R study also looked at consolidation in a real-world setting, and confirmed a PFS benefit with durvalumab in stage III NSCLC patients who had completed concurrent or sequential platinum-based CRT within the previous 12 weeks without evidence of disease progression (Abstract 1171MO).
“The median real-world PFS in this cohort was 21.7 months, which is higher than that in the durvalumab arm in the PACIFIC trial, which was 16.9 months,” reported Nicolas Girard, MD, a professor at Institut Curie, Paris.
The PACIFIC trial set the standard for durvalumab-based consolidation after CRT, and ongoing survival benefit was confirmed by 5-year follow-up data, he noted.
The PACIFIC-R trial included 1,399 patients from 11 countries who were treated as part of an expanded-access program following the PACIFIC trial.
Median time to durvalumab initiation after the end of radiotherapy in the cohort was 56 days. Overall median durvalumab treatment duration was 11 months, and the median number of infusions was 22, Dr. Girard said.
Pneumonitis was the most common adverse event leading to discontinuation: 214 (18.5%) patients experienced any-grade pneumonitis and/or interstitial lung disease, and 9.5 discontinued the study as a result. Most cases were mild or moderate, he said.
Subgroup analyses showed that real-world PFS was higher among patients with stage IIIa disease and those with PD-L1–positive tumors, those with nonsquamous disease histology, and those who received concurrent CRT.
“For example, in those with stage IIIa disease, the median real-world PFS was 23.7 months versus 19.2 months in patients with stage IIIb and c disease,” he said.
“PACIFIC-R demonstrated the efficacy of durvalumab consolidation in patients with unresectable stage III non–small cell lung cancer after completion of chemoradiotherapy,” said Dr. Girard. “The effectiveness of durvalumab was consistent among key subgroups, as was safety, when comparing the data with that of PACIFIC.
“The future read-outs of OS will further provide insight into the effectiveness of this regimen.”
Session chair Lizza E. Hendriks, MD, PhD, of Maastricht (the Netherlands) University, applauded the inclusion of patients undergoing sequential CRT in the GEMSTONE-301 and PACIFIC-R studies, noting that it is “very important to have data in sequential radiochemotherapy populations” given the substantial number of patients who require a sequential approach because of poor performance status, difficulty tolerating concurrent CRT, or logistical reasons, such as an inability to travel to receive concurrent CRT.
The GEMSTONE-301 study was funded by CStone Pharmaceuticals. Dr. Wu reported having no disclosures. The PACIFIC-R study was funded by AstraZeneca. Dr. Girard reported financial relationships with AstraZeneca, Bristol Myers Squibb, and Merck Sharp & Dohme. Dr. Hendriks reported financial relationships with numerous companies.
FROM ESMO 2021
Once daily poziotinib shows efficacy in non–small cell lung cancer
Tumor reductions, stated lead author Robin Cornelissen, PhD, MD, Erasmus University, Rotterdam, the Netherlands, were seen in 88% of patients.
EGFR and HER2 exon 20 insertion mutations are rare subsets accounting for about 10% each of all mutations and 2%-4% each in NSCLC. “There is no approved therapy for either treatment-naive or previously treated NSCLC with HER2 exon 20 mutations,” Dr. Cornelissen said in a virtual oral presentation (abstract LBA46) on Sept. 18. While chemotherapy agents with or without checkpoint inhibitors and tyrosine kinase inhibitors (TKIs) are currently utilized, none are specific to exon 20 mutations, and historical response rates from mostly small uncontrolled studies vary widely from about 6.9%-35%, with median progression-free survival (PFS) ranging from 3 to 7 months. Poziotinib is a potent oral pan-HER TKI with activity in patients with EGFR or HER2 exon 20–mutated NSCLC.
Dr. Cornelissen presented preliminary safety and efficacy data from the phase 2 ZENITH20, a seven-cohort global clinical trial, specifically from cohort 4 (daily dosing) which included 48 HER2 exon 20 insertion NSCLC patients (median age, 60.5 years; female/male, 26/22) treated first-line with oral daily poziotinib (16 mg). The majority were White (75%), female (54%), and nonsmokers (69%) with an Eastern Cooperative Oncology Group performance status of 1 (65%).The primary endpoint was objective response rate evaluated centrally by an independent image review committee using RECIST 1.1 criteria.
All patients have experienced treatment-related adverse events (TRAEs) with 10% considered serious, and permanent discontinuation in 13%. About 83% of patients had dose interruptions and 76% had dose reductions. The most common adverse events were diarrhea (any grade, 83%; grade 3, 15%), rash (any grade, 69%; grade 3, 35%), stomatitis/mucosal inflammation (any grade, 81%; grade 3, 21%), and paronychia (any grade, 46%; grade 3 8%). Pneumonitis occurred in two patients (4%), with one grade 3 (2%). No grade 4/5 TRAEs were reported.
Discontinuations in 44 patients (92%), Dr. Cornelissen said, are attributed to death (5/10%), disease progression (30/63%), adverse events (1/2%), and other (8/17%), with treatment ongoing in 4 patients (8%).
The rate for the primary endpoint of ORR was 43.8% (n = 21) (95% confidence interval, 29.5%-58.8%).Tumor reductions have been observed in 42/48 patients (88%) with a median reduction of 35%. One complete response was reported (2.1%), with partial responses in 20 (41.7%), stable disease in 15 (31.3%), progressive disease in 7 (14.6%), and 5 (10.4%) not evaluable. The disease control rate was 75.0%.
Among secondary endpoints, median duration of response (DoR) was 5.4 months (range, 2.8 to >19.1), with 42% of patients having response duration greater than6 months and 24% greater than 12 months. Median PFS was 5.6 months (range, 0 to >20.2), with progression-free survival duration greater than6 months in 42% and duration greater than12 months in 26%.
Dr. Cornelissen concluded: “Poziotinib shows clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.” The toxicity profile, he added, is manageable and in line with previous poziotinib studies and other second-generation EGFR TKIs.
Noting that improved tolerability and antitumor activity have been observed in the cohort 5 (8 mg b.i.d.) interim analysis, Dr. Cornelissen said that cohort 4 is ongoing with patients enrolling at 8-mg b.i.d. dosing.
HER2 mutations represents 1.7%-2.2% of NSCLC, with high-sequence homology with EGFR mutation, observed ESMO-appointed discussant Daniel S.W. Tan, PhD, National Cancer Center in Singapore. He pointed out that, while HER2 antibody drug conjugates and TKIs have gained approval in other cancer types (e.g., breast, gastric), currently no HER2 therapies are approved in NSCLC. Reviewing ZENITH20 findings (risk ratio, 43.8%; DoR, 5.4 months; PFS, 5.6 months), Dr. Tan stated that poziotinib is an active agent in HER2 mutated NSCLC. “One concern that remains for me is the safety profile that will require further evaluation in order to determine optimal dosing,” he said.
Potential combinations, he added, need to be explored to improve the durability of response. “Until we can properly characterize this and other important aspects such as CNS activity, we need to be cautious about transitioning to a frontline setting. Also, we do need to give due consideration to strategies to improve HER2 testing rates in order to expand on clinical experience. This argues for the importance of broad upfront next generation sequencing testing in NSCLC.”
The study was funded by Spectrum Pharmaceuticals. Other authors associated with the research disclosed full or part-time employment with Spectrum.
Tumor reductions, stated lead author Robin Cornelissen, PhD, MD, Erasmus University, Rotterdam, the Netherlands, were seen in 88% of patients.
EGFR and HER2 exon 20 insertion mutations are rare subsets accounting for about 10% each of all mutations and 2%-4% each in NSCLC. “There is no approved therapy for either treatment-naive or previously treated NSCLC with HER2 exon 20 mutations,” Dr. Cornelissen said in a virtual oral presentation (abstract LBA46) on Sept. 18. While chemotherapy agents with or without checkpoint inhibitors and tyrosine kinase inhibitors (TKIs) are currently utilized, none are specific to exon 20 mutations, and historical response rates from mostly small uncontrolled studies vary widely from about 6.9%-35%, with median progression-free survival (PFS) ranging from 3 to 7 months. Poziotinib is a potent oral pan-HER TKI with activity in patients with EGFR or HER2 exon 20–mutated NSCLC.
Dr. Cornelissen presented preliminary safety and efficacy data from the phase 2 ZENITH20, a seven-cohort global clinical trial, specifically from cohort 4 (daily dosing) which included 48 HER2 exon 20 insertion NSCLC patients (median age, 60.5 years; female/male, 26/22) treated first-line with oral daily poziotinib (16 mg). The majority were White (75%), female (54%), and nonsmokers (69%) with an Eastern Cooperative Oncology Group performance status of 1 (65%).The primary endpoint was objective response rate evaluated centrally by an independent image review committee using RECIST 1.1 criteria.
All patients have experienced treatment-related adverse events (TRAEs) with 10% considered serious, and permanent discontinuation in 13%. About 83% of patients had dose interruptions and 76% had dose reductions. The most common adverse events were diarrhea (any grade, 83%; grade 3, 15%), rash (any grade, 69%; grade 3, 35%), stomatitis/mucosal inflammation (any grade, 81%; grade 3, 21%), and paronychia (any grade, 46%; grade 3 8%). Pneumonitis occurred in two patients (4%), with one grade 3 (2%). No grade 4/5 TRAEs were reported.
Discontinuations in 44 patients (92%), Dr. Cornelissen said, are attributed to death (5/10%), disease progression (30/63%), adverse events (1/2%), and other (8/17%), with treatment ongoing in 4 patients (8%).
The rate for the primary endpoint of ORR was 43.8% (n = 21) (95% confidence interval, 29.5%-58.8%).Tumor reductions have been observed in 42/48 patients (88%) with a median reduction of 35%. One complete response was reported (2.1%), with partial responses in 20 (41.7%), stable disease in 15 (31.3%), progressive disease in 7 (14.6%), and 5 (10.4%) not evaluable. The disease control rate was 75.0%.
Among secondary endpoints, median duration of response (DoR) was 5.4 months (range, 2.8 to >19.1), with 42% of patients having response duration greater than6 months and 24% greater than 12 months. Median PFS was 5.6 months (range, 0 to >20.2), with progression-free survival duration greater than6 months in 42% and duration greater than12 months in 26%.
Dr. Cornelissen concluded: “Poziotinib shows clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.” The toxicity profile, he added, is manageable and in line with previous poziotinib studies and other second-generation EGFR TKIs.
Noting that improved tolerability and antitumor activity have been observed in the cohort 5 (8 mg b.i.d.) interim analysis, Dr. Cornelissen said that cohort 4 is ongoing with patients enrolling at 8-mg b.i.d. dosing.
HER2 mutations represents 1.7%-2.2% of NSCLC, with high-sequence homology with EGFR mutation, observed ESMO-appointed discussant Daniel S.W. Tan, PhD, National Cancer Center in Singapore. He pointed out that, while HER2 antibody drug conjugates and TKIs have gained approval in other cancer types (e.g., breast, gastric), currently no HER2 therapies are approved in NSCLC. Reviewing ZENITH20 findings (risk ratio, 43.8%; DoR, 5.4 months; PFS, 5.6 months), Dr. Tan stated that poziotinib is an active agent in HER2 mutated NSCLC. “One concern that remains for me is the safety profile that will require further evaluation in order to determine optimal dosing,” he said.
Potential combinations, he added, need to be explored to improve the durability of response. “Until we can properly characterize this and other important aspects such as CNS activity, we need to be cautious about transitioning to a frontline setting. Also, we do need to give due consideration to strategies to improve HER2 testing rates in order to expand on clinical experience. This argues for the importance of broad upfront next generation sequencing testing in NSCLC.”
The study was funded by Spectrum Pharmaceuticals. Other authors associated with the research disclosed full or part-time employment with Spectrum.
Tumor reductions, stated lead author Robin Cornelissen, PhD, MD, Erasmus University, Rotterdam, the Netherlands, were seen in 88% of patients.
EGFR and HER2 exon 20 insertion mutations are rare subsets accounting for about 10% each of all mutations and 2%-4% each in NSCLC. “There is no approved therapy for either treatment-naive or previously treated NSCLC with HER2 exon 20 mutations,” Dr. Cornelissen said in a virtual oral presentation (abstract LBA46) on Sept. 18. While chemotherapy agents with or without checkpoint inhibitors and tyrosine kinase inhibitors (TKIs) are currently utilized, none are specific to exon 20 mutations, and historical response rates from mostly small uncontrolled studies vary widely from about 6.9%-35%, with median progression-free survival (PFS) ranging from 3 to 7 months. Poziotinib is a potent oral pan-HER TKI with activity in patients with EGFR or HER2 exon 20–mutated NSCLC.
Dr. Cornelissen presented preliminary safety and efficacy data from the phase 2 ZENITH20, a seven-cohort global clinical trial, specifically from cohort 4 (daily dosing) which included 48 HER2 exon 20 insertion NSCLC patients (median age, 60.5 years; female/male, 26/22) treated first-line with oral daily poziotinib (16 mg). The majority were White (75%), female (54%), and nonsmokers (69%) with an Eastern Cooperative Oncology Group performance status of 1 (65%).The primary endpoint was objective response rate evaluated centrally by an independent image review committee using RECIST 1.1 criteria.
All patients have experienced treatment-related adverse events (TRAEs) with 10% considered serious, and permanent discontinuation in 13%. About 83% of patients had dose interruptions and 76% had dose reductions. The most common adverse events were diarrhea (any grade, 83%; grade 3, 15%), rash (any grade, 69%; grade 3, 35%), stomatitis/mucosal inflammation (any grade, 81%; grade 3, 21%), and paronychia (any grade, 46%; grade 3 8%). Pneumonitis occurred in two patients (4%), with one grade 3 (2%). No grade 4/5 TRAEs were reported.
Discontinuations in 44 patients (92%), Dr. Cornelissen said, are attributed to death (5/10%), disease progression (30/63%), adverse events (1/2%), and other (8/17%), with treatment ongoing in 4 patients (8%).
The rate for the primary endpoint of ORR was 43.8% (n = 21) (95% confidence interval, 29.5%-58.8%).Tumor reductions have been observed in 42/48 patients (88%) with a median reduction of 35%. One complete response was reported (2.1%), with partial responses in 20 (41.7%), stable disease in 15 (31.3%), progressive disease in 7 (14.6%), and 5 (10.4%) not evaluable. The disease control rate was 75.0%.
Among secondary endpoints, median duration of response (DoR) was 5.4 months (range, 2.8 to >19.1), with 42% of patients having response duration greater than6 months and 24% greater than 12 months. Median PFS was 5.6 months (range, 0 to >20.2), with progression-free survival duration greater than6 months in 42% and duration greater than12 months in 26%.
Dr. Cornelissen concluded: “Poziotinib shows clinically meaningful efficacy for treatment-naive NSCLC HER2 exon 20 mutations with [daily] dosing.” The toxicity profile, he added, is manageable and in line with previous poziotinib studies and other second-generation EGFR TKIs.
Noting that improved tolerability and antitumor activity have been observed in the cohort 5 (8 mg b.i.d.) interim analysis, Dr. Cornelissen said that cohort 4 is ongoing with patients enrolling at 8-mg b.i.d. dosing.
HER2 mutations represents 1.7%-2.2% of NSCLC, with high-sequence homology with EGFR mutation, observed ESMO-appointed discussant Daniel S.W. Tan, PhD, National Cancer Center in Singapore. He pointed out that, while HER2 antibody drug conjugates and TKIs have gained approval in other cancer types (e.g., breast, gastric), currently no HER2 therapies are approved in NSCLC. Reviewing ZENITH20 findings (risk ratio, 43.8%; DoR, 5.4 months; PFS, 5.6 months), Dr. Tan stated that poziotinib is an active agent in HER2 mutated NSCLC. “One concern that remains for me is the safety profile that will require further evaluation in order to determine optimal dosing,” he said.
Potential combinations, he added, need to be explored to improve the durability of response. “Until we can properly characterize this and other important aspects such as CNS activity, we need to be cautious about transitioning to a frontline setting. Also, we do need to give due consideration to strategies to improve HER2 testing rates in order to expand on clinical experience. This argues for the importance of broad upfront next generation sequencing testing in NSCLC.”
The study was funded by Spectrum Pharmaceuticals. Other authors associated with the research disclosed full or part-time employment with Spectrum.
FROM ESMO 2021
Atezolizumab plus chemotherapy superior to best supportive care in early lung cancer
according to Enriqueta Felip, MD, the head of thoracic and head and neck cancer unit at Vall d’Hebron Institute of Oncology, Hospital, Barcelona.
IMpower010 is the first positive randomized phase 3 study to show significant disease-free survival (DFS) improvement with adjuvant cancer immunotherapy (atezolizumab, anti–programmed death–ligand 1, and platinum-based chemotherapy) in this population, Dr. Felip said in a presentation at the 2021 European Society for Medical Oncology Congress on Sept. 20 (abstract LBA9).
High unmet need
Up to 60% of patients with stage I-III NSCLC still experience disease relapse despite having received treatment, Dr. Felip said. IMpower010 included 1,280 patients who received up to four cycles of chemotherapy (cisplatin with pemetrexed, gemcitabine, docetaxel, or vinorelbine) after completely resected stage IB-IIIA NSCLC. Patients were randomized to open label to atezolizumab (1,200 mg every 21 days for 16 cycles or best supportive care (BSC). The primary endpoint of investigator-assessed DFS in the stage II-IIIA population (n = 1,005) was stratified according to three groups: PD-L1 tumor cells of at least 1% (stage II-IIIA), all-randomized (stage II-IIIA) and intention-to-treat (stage IB-IIIA).
Median disease-free survival in PD-L1 tumor cells of at least 1% was not estimated in the atezolizumab group and was 35.3 months in the BSC group (95% CI, 29.0 to NE). In the all-randomized group, median DFS was 42.3 months in the atezolizumab group (95% CI, 36.0 to NE) and 35.3 months in the BSC group (95% CI, 30.4-46.4) with a stratified hazard ratio of 0.79 (95% CI, 0.64-0.96; P = .02). In the intent-to-treat population, median DFS was not evaluable in the atezolizumab group and 37.2 months in the BSC group (95% CI, 31.6 to NE) with a hazard ratio of 0.81 (95% CI, 0.67-0.99; P = .04).
DFS hazard ratio 0.43 in TC ≥50% group
Looking at DFS by PD-L1 status in the population with and without known EGFR/ALK+ disease, Dr. Felip said that the hazard ratio for the tumor cells of at least 50% group (n = 229) was 0.43 (95% CI, 0.27-0.68), as compared with 0.87 (95% CI, 0.60-1.26) for the tumor cells 1%-49% group. With EGFR/ALK+ patients excluded, the respective HRs were similar (0.43/0.82). Considering DFS events including only disease recurrence, disease incidence was 29.4%/44.7% in the atezolizumab and BSC groups, respectively for those with PD-L1 tumor cells of at least 1%. The same pattern of atezolizumab benefit persisted in the all-randomized and intent-to-treat groups.
An assessment according to regions of relapse (locoregional only, distant only, locoregional and distant, CNS only, second primary lung) revealed no differences in the three groups. Analysis of time from randomization to relapse revealed regional differences in the PD-L1 tumor cells of at least 1% group with a median time to any relapse of 17.6 months in the atezolizumab group and 10.9 months in the BSC group. Time from randomization to relapse was generally similar for atezolizumab and best supportive care in the all randomized and intent-to-treat groups (about 11-12 months).
“The greatest magnitude of disease-free survival benefit was observed in the PD-L1 tumor cell of at least 50% population with a hazard ratio of 0.43,” Dr. Felip said. In a post hoc analysis excluding patients with known EFGR/ALK with NSCLC, she said that hazard ratios were numerically improved in most PD-L1 subgroups. Postrelapse cancer immunotherapies were used at a higher rate in the BSC arm of the trial. “Longer-term follow-up is warranted and may reveal differences in relapse patterns and treatment options.
Playing with the immune system
Benjamin Besse, MD, director of oncology and chair of the EORTC Lung Group at Paris-Saclay University, acknowledged the disease-free survival benefit with atezolizumab in IMpower010 and underscored that adjuvant immunotherapy has been changing treatment in resected cancers across tumor types (i.e., melanoma, renal cell carcinoma, NSCLC). He voiced some concerns, including the absence of benefit in PD-L1 less than 1%, pneumonectomy and EGFRmut/ALK+ patients, and generally the potential “when you play with the immune system for there to be a dark side too.” Dr. Besse said delayed side effects in 43.2% of patients , citing a recent report of chronic, mostly grade 1-2 immune-related adverse events following (>12 weeks after discontinuation) adjuvant anti–PD-1 therapy for high-risk resected melanoma. He mentioned, however, that the rate of second primary lung tumors in the atezolizumab group (1.4%) was lower than in the BSC group (2.6%), with generally similar rates between immuno- and nonimmunotherapies in melanoma and breast cancer trials.
“IMpower 010 is the first adjuvant study establishing immune checkpoint blockade as a new standard of care. We need to cure more, not to delay relapse,” he said. The optimal population for treatment is still yet to be defined, as is the best perioperative strategy, Dr. Besse added. “If approved I would prescribe adjuvant atezolizumab ... until I see the overall survival curves.”
IMpower010 was funded by–F. Hoffmann-La Roche. Dr. Felip disclosed numerous financial interests, including having received financial support from F. Hoffmann–La Roche, AstraZeneca, Amgen, and Merck, among other pharmaceutical companies.
according to Enriqueta Felip, MD, the head of thoracic and head and neck cancer unit at Vall d’Hebron Institute of Oncology, Hospital, Barcelona.
IMpower010 is the first positive randomized phase 3 study to show significant disease-free survival (DFS) improvement with adjuvant cancer immunotherapy (atezolizumab, anti–programmed death–ligand 1, and platinum-based chemotherapy) in this population, Dr. Felip said in a presentation at the 2021 European Society for Medical Oncology Congress on Sept. 20 (abstract LBA9).
High unmet need
Up to 60% of patients with stage I-III NSCLC still experience disease relapse despite having received treatment, Dr. Felip said. IMpower010 included 1,280 patients who received up to four cycles of chemotherapy (cisplatin with pemetrexed, gemcitabine, docetaxel, or vinorelbine) after completely resected stage IB-IIIA NSCLC. Patients were randomized to open label to atezolizumab (1,200 mg every 21 days for 16 cycles or best supportive care (BSC). The primary endpoint of investigator-assessed DFS in the stage II-IIIA population (n = 1,005) was stratified according to three groups: PD-L1 tumor cells of at least 1% (stage II-IIIA), all-randomized (stage II-IIIA) and intention-to-treat (stage IB-IIIA).
Median disease-free survival in PD-L1 tumor cells of at least 1% was not estimated in the atezolizumab group and was 35.3 months in the BSC group (95% CI, 29.0 to NE). In the all-randomized group, median DFS was 42.3 months in the atezolizumab group (95% CI, 36.0 to NE) and 35.3 months in the BSC group (95% CI, 30.4-46.4) with a stratified hazard ratio of 0.79 (95% CI, 0.64-0.96; P = .02). In the intent-to-treat population, median DFS was not evaluable in the atezolizumab group and 37.2 months in the BSC group (95% CI, 31.6 to NE) with a hazard ratio of 0.81 (95% CI, 0.67-0.99; P = .04).
DFS hazard ratio 0.43 in TC ≥50% group
Looking at DFS by PD-L1 status in the population with and without known EGFR/ALK+ disease, Dr. Felip said that the hazard ratio for the tumor cells of at least 50% group (n = 229) was 0.43 (95% CI, 0.27-0.68), as compared with 0.87 (95% CI, 0.60-1.26) for the tumor cells 1%-49% group. With EGFR/ALK+ patients excluded, the respective HRs were similar (0.43/0.82). Considering DFS events including only disease recurrence, disease incidence was 29.4%/44.7% in the atezolizumab and BSC groups, respectively for those with PD-L1 tumor cells of at least 1%. The same pattern of atezolizumab benefit persisted in the all-randomized and intent-to-treat groups.
An assessment according to regions of relapse (locoregional only, distant only, locoregional and distant, CNS only, second primary lung) revealed no differences in the three groups. Analysis of time from randomization to relapse revealed regional differences in the PD-L1 tumor cells of at least 1% group with a median time to any relapse of 17.6 months in the atezolizumab group and 10.9 months in the BSC group. Time from randomization to relapse was generally similar for atezolizumab and best supportive care in the all randomized and intent-to-treat groups (about 11-12 months).
“The greatest magnitude of disease-free survival benefit was observed in the PD-L1 tumor cell of at least 50% population with a hazard ratio of 0.43,” Dr. Felip said. In a post hoc analysis excluding patients with known EFGR/ALK with NSCLC, she said that hazard ratios were numerically improved in most PD-L1 subgroups. Postrelapse cancer immunotherapies were used at a higher rate in the BSC arm of the trial. “Longer-term follow-up is warranted and may reveal differences in relapse patterns and treatment options.
Playing with the immune system
Benjamin Besse, MD, director of oncology and chair of the EORTC Lung Group at Paris-Saclay University, acknowledged the disease-free survival benefit with atezolizumab in IMpower010 and underscored that adjuvant immunotherapy has been changing treatment in resected cancers across tumor types (i.e., melanoma, renal cell carcinoma, NSCLC). He voiced some concerns, including the absence of benefit in PD-L1 less than 1%, pneumonectomy and EGFRmut/ALK+ patients, and generally the potential “when you play with the immune system for there to be a dark side too.” Dr. Besse said delayed side effects in 43.2% of patients , citing a recent report of chronic, mostly grade 1-2 immune-related adverse events following (>12 weeks after discontinuation) adjuvant anti–PD-1 therapy for high-risk resected melanoma. He mentioned, however, that the rate of second primary lung tumors in the atezolizumab group (1.4%) was lower than in the BSC group (2.6%), with generally similar rates between immuno- and nonimmunotherapies in melanoma and breast cancer trials.
“IMpower 010 is the first adjuvant study establishing immune checkpoint blockade as a new standard of care. We need to cure more, not to delay relapse,” he said. The optimal population for treatment is still yet to be defined, as is the best perioperative strategy, Dr. Besse added. “If approved I would prescribe adjuvant atezolizumab ... until I see the overall survival curves.”
IMpower010 was funded by–F. Hoffmann-La Roche. Dr. Felip disclosed numerous financial interests, including having received financial support from F. Hoffmann–La Roche, AstraZeneca, Amgen, and Merck, among other pharmaceutical companies.
according to Enriqueta Felip, MD, the head of thoracic and head and neck cancer unit at Vall d’Hebron Institute of Oncology, Hospital, Barcelona.
IMpower010 is the first positive randomized phase 3 study to show significant disease-free survival (DFS) improvement with adjuvant cancer immunotherapy (atezolizumab, anti–programmed death–ligand 1, and platinum-based chemotherapy) in this population, Dr. Felip said in a presentation at the 2021 European Society for Medical Oncology Congress on Sept. 20 (abstract LBA9).
High unmet need
Up to 60% of patients with stage I-III NSCLC still experience disease relapse despite having received treatment, Dr. Felip said. IMpower010 included 1,280 patients who received up to four cycles of chemotherapy (cisplatin with pemetrexed, gemcitabine, docetaxel, or vinorelbine) after completely resected stage IB-IIIA NSCLC. Patients were randomized to open label to atezolizumab (1,200 mg every 21 days for 16 cycles or best supportive care (BSC). The primary endpoint of investigator-assessed DFS in the stage II-IIIA population (n = 1,005) was stratified according to three groups: PD-L1 tumor cells of at least 1% (stage II-IIIA), all-randomized (stage II-IIIA) and intention-to-treat (stage IB-IIIA).
Median disease-free survival in PD-L1 tumor cells of at least 1% was not estimated in the atezolizumab group and was 35.3 months in the BSC group (95% CI, 29.0 to NE). In the all-randomized group, median DFS was 42.3 months in the atezolizumab group (95% CI, 36.0 to NE) and 35.3 months in the BSC group (95% CI, 30.4-46.4) with a stratified hazard ratio of 0.79 (95% CI, 0.64-0.96; P = .02). In the intent-to-treat population, median DFS was not evaluable in the atezolizumab group and 37.2 months in the BSC group (95% CI, 31.6 to NE) with a hazard ratio of 0.81 (95% CI, 0.67-0.99; P = .04).
DFS hazard ratio 0.43 in TC ≥50% group
Looking at DFS by PD-L1 status in the population with and without known EGFR/ALK+ disease, Dr. Felip said that the hazard ratio for the tumor cells of at least 50% group (n = 229) was 0.43 (95% CI, 0.27-0.68), as compared with 0.87 (95% CI, 0.60-1.26) for the tumor cells 1%-49% group. With EGFR/ALK+ patients excluded, the respective HRs were similar (0.43/0.82). Considering DFS events including only disease recurrence, disease incidence was 29.4%/44.7% in the atezolizumab and BSC groups, respectively for those with PD-L1 tumor cells of at least 1%. The same pattern of atezolizumab benefit persisted in the all-randomized and intent-to-treat groups.
An assessment according to regions of relapse (locoregional only, distant only, locoregional and distant, CNS only, second primary lung) revealed no differences in the three groups. Analysis of time from randomization to relapse revealed regional differences in the PD-L1 tumor cells of at least 1% group with a median time to any relapse of 17.6 months in the atezolizumab group and 10.9 months in the BSC group. Time from randomization to relapse was generally similar for atezolizumab and best supportive care in the all randomized and intent-to-treat groups (about 11-12 months).
“The greatest magnitude of disease-free survival benefit was observed in the PD-L1 tumor cell of at least 50% population with a hazard ratio of 0.43,” Dr. Felip said. In a post hoc analysis excluding patients with known EFGR/ALK with NSCLC, she said that hazard ratios were numerically improved in most PD-L1 subgroups. Postrelapse cancer immunotherapies were used at a higher rate in the BSC arm of the trial. “Longer-term follow-up is warranted and may reveal differences in relapse patterns and treatment options.
Playing with the immune system
Benjamin Besse, MD, director of oncology and chair of the EORTC Lung Group at Paris-Saclay University, acknowledged the disease-free survival benefit with atezolizumab in IMpower010 and underscored that adjuvant immunotherapy has been changing treatment in resected cancers across tumor types (i.e., melanoma, renal cell carcinoma, NSCLC). He voiced some concerns, including the absence of benefit in PD-L1 less than 1%, pneumonectomy and EGFRmut/ALK+ patients, and generally the potential “when you play with the immune system for there to be a dark side too.” Dr. Besse said delayed side effects in 43.2% of patients , citing a recent report of chronic, mostly grade 1-2 immune-related adverse events following (>12 weeks after discontinuation) adjuvant anti–PD-1 therapy for high-risk resected melanoma. He mentioned, however, that the rate of second primary lung tumors in the atezolizumab group (1.4%) was lower than in the BSC group (2.6%), with generally similar rates between immuno- and nonimmunotherapies in melanoma and breast cancer trials.
“IMpower 010 is the first adjuvant study establishing immune checkpoint blockade as a new standard of care. We need to cure more, not to delay relapse,” he said. The optimal population for treatment is still yet to be defined, as is the best perioperative strategy, Dr. Besse added. “If approved I would prescribe adjuvant atezolizumab ... until I see the overall survival curves.”
IMpower010 was funded by–F. Hoffmann-La Roche. Dr. Felip disclosed numerous financial interests, including having received financial support from F. Hoffmann–La Roche, AstraZeneca, Amgen, and Merck, among other pharmaceutical companies.
FROM ESMO 2021
Study supports chemotherapy with immunotherapy for some never-smokers with lung cancer
Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).
However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.
She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.
Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.
The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.
“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.
The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.
Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.
Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.
For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.
The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.
“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.
Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.
Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.
This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.
Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).
However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.
She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.
Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.
The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.
“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.
The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.
Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.
Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.
For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.
The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.
“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.
Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.
Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.
This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.
Median overall survival was similar at 21.0 months and 22.1 months in 169 patients who received cancer immunotherapy plus chemotherapy and 351 who received cancer immunotherapy monotherapy, respectively (adjusted hazard ratio, 1.03). Median real-world progression-free survival (PFS) was also similar in the two groups (10.8 vs. 11.5 months; aHR, 1.04), Solange Peters, MD, reported at the 2021 European Society for Medical Oncology Congress on Sept. 17 (abstract VP2_2021).
However, in a small subgroup of 50 never-smokers, CIT plus chemotherapy showed significant and meaningful improvement in both overall survival and real-world progression-free survival, compared with CIT monotherapy, said Dr. Peters, ESMO president and professor and chair of medical oncology at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
The hazard ratios for overall survival and progression-free survival, after adjusting for baseline characteristics, were 0.50 and 0.40 in this subgroup, Dr. Peters said.
She and her colleagues reviewed data from the nationwide Flatiron Health Electronic Health Record–derived deidentified database for patients with metastatic nonsquamous NSCLC with a PD-L1 tumor proportion score at least 50% expression who initiated first-line CIT monotherapy or CIT plus chemotherapy between Oct. 24, 2016, and Feb. 28, 2019.
Median follow-up was 23.5 and 19.9 months in the monotherapy and combination therapy groups, respectively.
The findings are notable because “this is a very important scientific question, which by the way, is a daily question we have,” Dr. Peters said during a plenary debate session at the conference.
“One in four patients [with metastatic nonsquamous NSCLC has] this high PDL expression,” she explained, noting that both treatment approaches are commonly used in the first-line setting in this patient population.
The findings highlight the value of “well-conducted real-world evidence trials” in the absence of randomized trial results, she said.
Invited discussant Marina Chiara Garassino, MBBS, professor of medicine at the University of Chicago, also acknowledged the importance of the findings, noting the “multiple possibilities” for treatment selection in the metastatic nonsquamous NSCLC patient population.
Although patients with PD-L1 expression below 50% derive clear benefit from combination versus single-agent therapy, treatment selection for those with high PD-L1 expression is “very tricky and debatable,” she said.
For those with high PD-L1 expression, the choice is less clear and wrought with uncertainties – particularly for certain subgroups like never-smokers and those with PD-L1 expression over 90%, she said.
The findings reinforce those seen in prior meta-analyses and other clinical trials, particularly with respect to the role of smoking history when making treatment decisions.
“After these results and previous subgroup analyses, in my opinion, in [patients with] PD-L1 expression over 50%, we should consider the combination of chemotherapy and immunotherapy,” she said.
Conversely, findings from this study showing no difference in outcomes between the treatment approaches in patients with brain or liver metastases are based on small numbers and lack power for drawing any conclusions, she said. It also remains unclear whether there is a differential effect for women and those with PD-L1 expression over 90%, high tumor mutation burden, performance score greater than 2, and age over 75 years.
Both Dr. Garassino and Dr. Peters said they are looking to the INSIGNA trial, which is currently recruiting patients in the United States to evaluate the timing of pembrolizumab alone or with chemotherapy as first-line treatment and maintenance in NSCLC, to provide more clarification regarding the best treatment approaches.
This study was funded by F. Hoffmann–La Roche. Dr. Peters and Dr. Garassino each disclosed personal and/or institutional financial relationships with numerous pharmaceutical companies.
FROM ESMO 2021
Should Geriatric Veterans Get Immunotherapy?
Patients in their 90s with cancer tolerated immunotherapy well with few serious adverse effects, and they lived for an average of 1.6 years after treatment, a small new study within the US Department of Veterans Affairs (VA) health system reports.
Only 6.3% of 48 patients who were treated with immune checkpoint inhibitors experienced the most severe types of side effects – grade III/IV events – and a total of 27% had any adverse effects, according to the report, which was presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and inperson in Denver Colorado, September 24 to September 26, 2021.
“Our project should help give confidence to oncologists treating the elderly,” said Andrew Joseph Benefield, MD, a hematology/oncology fellow at Wake Forest Baptist Medical Center, in an interview. “Immunotherapy can be given safely and likely effectively in select individuals over the age of 90 with good performance status.”
Benefield and colleagues launched their study to gain insight into a little-studied area: How does cancer treatment affects nonagenarians? “I think many oncologists have been in a situation where they encounter an individual over the age of 90 years who has a good performance status, and they've wondered if immunotherapy would be helpful and safe, particularly given our knowledge of waning immune strength as people age,” he said.
The researchers retrospectively tracked patients with cancer who were at least 90 years old from 2016 to 2017 and were treated with immune checkpoint inhibitors. Most were fit or fairly fit with Eastern Cooperative Oncology Group (ECOG) physical performance scales of 0 or 1 (n = 26), and nearly all had cancer in stage IV (n = 42). Melanoma was the most common type of cancer (n = 19), followed by non-small-cell lung cancer (n = 15). Patients were treated with an average of 12.2 cycles.
“In general, we saw that treatment was well-tolerated,” Dr. Benefield said. “We also noted that a trend toward better long-term survival outcomes in individuals with very good performance status at the start of treatment. We hope to parse this out more as we add more data to our data-set, as the numbers are still too small for confident direct comparison.”
Dr. Benefield said he has treated a limited number of patients in their 90s who were highly physical fit for their age and “very eager” to be treated. “They wanted to do anything they could to maintain their lifestyle,” he said. “In my experience, aggressive supportive care and close monitoring for developing toxicities has been most helpful.”
The researchers don’t know the causes of death of many of the patients, and it’s not clear how they fared in their final days. Still, Dr. Benefield said, “extending someone's life by more than 1 year with relatively low risk of adverse effects is reasonable.”
Oncologist Melisa Wong, MD, MAS, of the University of California, San Francisco, reviewed the study and said in an interview that it “a valuable description of outcomes for nonagenarians receiving immunotherapy in the VA healthcare system.” As she noted, “many other studies of immunotherapy among older adults focus on patients aged 65 or 70 and older while very few focus on octogenarians or nonagenarians.”
The findings suggest that “it is important to move beyond chronological age and assess patients’ physiologic age through a geriatric assessment,” she said. “Geriatric assessment-derived risk scores have been shown to predict chemotherapy toxicity for older adults and research to develop similar tools for immunotherapy are ongoing.”
However, she cautioned that older patients may become suffer so much from the most common side effect of immunotherapy -- fatigue – that “their independence is at stake.”
“Some of these patient choose to stop immunotherapy because the side effects aren’t worth it anymore,” she said. “The challenge for oncologists is not knowing in advance which patients will fall into each of these categories.”
She added that her geriatric oncology research focuses on improving risk stratification for older adults, such as those who are at least 70 with lung adenocarcinoma.
Oncologist Grant R. Williams, MD, MSPH, director of the Cancer & Aging Program at the University of Alabama at Birmingham, agreed in an interview that comprehensive geriatric assessments are important to guide treatment in the oldest adults. “In addition, it is important to elicit the goals of treatment as well,” he said. “For older adults that are fit or at least pre-frail and desire aggressive treatment, immunotherapy is a very reasonable approach, particularly when patients are closely monitored for side effects.”
No study funding is reported. The authors report no disclosures. Dr. Wong discloses an immediate family member is an employee and stock holder of Genentech. Dr. Williams has no disclosures.
Patients in their 90s with cancer tolerated immunotherapy well with few serious adverse effects, and they lived for an average of 1.6 years after treatment, a small new study within the US Department of Veterans Affairs (VA) health system reports.
Only 6.3% of 48 patients who were treated with immune checkpoint inhibitors experienced the most severe types of side effects – grade III/IV events – and a total of 27% had any adverse effects, according to the report, which was presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and inperson in Denver Colorado, September 24 to September 26, 2021.
“Our project should help give confidence to oncologists treating the elderly,” said Andrew Joseph Benefield, MD, a hematology/oncology fellow at Wake Forest Baptist Medical Center, in an interview. “Immunotherapy can be given safely and likely effectively in select individuals over the age of 90 with good performance status.”
Benefield and colleagues launched their study to gain insight into a little-studied area: How does cancer treatment affects nonagenarians? “I think many oncologists have been in a situation where they encounter an individual over the age of 90 years who has a good performance status, and they've wondered if immunotherapy would be helpful and safe, particularly given our knowledge of waning immune strength as people age,” he said.
The researchers retrospectively tracked patients with cancer who were at least 90 years old from 2016 to 2017 and were treated with immune checkpoint inhibitors. Most were fit or fairly fit with Eastern Cooperative Oncology Group (ECOG) physical performance scales of 0 or 1 (n = 26), and nearly all had cancer in stage IV (n = 42). Melanoma was the most common type of cancer (n = 19), followed by non-small-cell lung cancer (n = 15). Patients were treated with an average of 12.2 cycles.
“In general, we saw that treatment was well-tolerated,” Dr. Benefield said. “We also noted that a trend toward better long-term survival outcomes in individuals with very good performance status at the start of treatment. We hope to parse this out more as we add more data to our data-set, as the numbers are still too small for confident direct comparison.”
Dr. Benefield said he has treated a limited number of patients in their 90s who were highly physical fit for their age and “very eager” to be treated. “They wanted to do anything they could to maintain their lifestyle,” he said. “In my experience, aggressive supportive care and close monitoring for developing toxicities has been most helpful.”
The researchers don’t know the causes of death of many of the patients, and it’s not clear how they fared in their final days. Still, Dr. Benefield said, “extending someone's life by more than 1 year with relatively low risk of adverse effects is reasonable.”
Oncologist Melisa Wong, MD, MAS, of the University of California, San Francisco, reviewed the study and said in an interview that it “a valuable description of outcomes for nonagenarians receiving immunotherapy in the VA healthcare system.” As she noted, “many other studies of immunotherapy among older adults focus on patients aged 65 or 70 and older while very few focus on octogenarians or nonagenarians.”
The findings suggest that “it is important to move beyond chronological age and assess patients’ physiologic age through a geriatric assessment,” she said. “Geriatric assessment-derived risk scores have been shown to predict chemotherapy toxicity for older adults and research to develop similar tools for immunotherapy are ongoing.”
However, she cautioned that older patients may become suffer so much from the most common side effect of immunotherapy -- fatigue – that “their independence is at stake.”
“Some of these patient choose to stop immunotherapy because the side effects aren’t worth it anymore,” she said. “The challenge for oncologists is not knowing in advance which patients will fall into each of these categories.”
She added that her geriatric oncology research focuses on improving risk stratification for older adults, such as those who are at least 70 with lung adenocarcinoma.
Oncologist Grant R. Williams, MD, MSPH, director of the Cancer & Aging Program at the University of Alabama at Birmingham, agreed in an interview that comprehensive geriatric assessments are important to guide treatment in the oldest adults. “In addition, it is important to elicit the goals of treatment as well,” he said. “For older adults that are fit or at least pre-frail and desire aggressive treatment, immunotherapy is a very reasonable approach, particularly when patients are closely monitored for side effects.”
No study funding is reported. The authors report no disclosures. Dr. Wong discloses an immediate family member is an employee and stock holder of Genentech. Dr. Williams has no disclosures.
Patients in their 90s with cancer tolerated immunotherapy well with few serious adverse effects, and they lived for an average of 1.6 years after treatment, a small new study within the US Department of Veterans Affairs (VA) health system reports.
Only 6.3% of 48 patients who were treated with immune checkpoint inhibitors experienced the most severe types of side effects – grade III/IV events – and a total of 27% had any adverse effects, according to the report, which was presented at the 2021 annual meeting of the Association of VA Hematology/Oncology (AVAHO) being held virtually and inperson in Denver Colorado, September 24 to September 26, 2021.
“Our project should help give confidence to oncologists treating the elderly,” said Andrew Joseph Benefield, MD, a hematology/oncology fellow at Wake Forest Baptist Medical Center, in an interview. “Immunotherapy can be given safely and likely effectively in select individuals over the age of 90 with good performance status.”
Benefield and colleagues launched their study to gain insight into a little-studied area: How does cancer treatment affects nonagenarians? “I think many oncologists have been in a situation where they encounter an individual over the age of 90 years who has a good performance status, and they've wondered if immunotherapy would be helpful and safe, particularly given our knowledge of waning immune strength as people age,” he said.
The researchers retrospectively tracked patients with cancer who were at least 90 years old from 2016 to 2017 and were treated with immune checkpoint inhibitors. Most were fit or fairly fit with Eastern Cooperative Oncology Group (ECOG) physical performance scales of 0 or 1 (n = 26), and nearly all had cancer in stage IV (n = 42). Melanoma was the most common type of cancer (n = 19), followed by non-small-cell lung cancer (n = 15). Patients were treated with an average of 12.2 cycles.
“In general, we saw that treatment was well-tolerated,” Dr. Benefield said. “We also noted that a trend toward better long-term survival outcomes in individuals with very good performance status at the start of treatment. We hope to parse this out more as we add more data to our data-set, as the numbers are still too small for confident direct comparison.”
Dr. Benefield said he has treated a limited number of patients in their 90s who were highly physical fit for their age and “very eager” to be treated. “They wanted to do anything they could to maintain their lifestyle,” he said. “In my experience, aggressive supportive care and close monitoring for developing toxicities has been most helpful.”
The researchers don’t know the causes of death of many of the patients, and it’s not clear how they fared in their final days. Still, Dr. Benefield said, “extending someone's life by more than 1 year with relatively low risk of adverse effects is reasonable.”
Oncologist Melisa Wong, MD, MAS, of the University of California, San Francisco, reviewed the study and said in an interview that it “a valuable description of outcomes for nonagenarians receiving immunotherapy in the VA healthcare system.” As she noted, “many other studies of immunotherapy among older adults focus on patients aged 65 or 70 and older while very few focus on octogenarians or nonagenarians.”
The findings suggest that “it is important to move beyond chronological age and assess patients’ physiologic age through a geriatric assessment,” she said. “Geriatric assessment-derived risk scores have been shown to predict chemotherapy toxicity for older adults and research to develop similar tools for immunotherapy are ongoing.”
However, she cautioned that older patients may become suffer so much from the most common side effect of immunotherapy -- fatigue – that “their independence is at stake.”
“Some of these patient choose to stop immunotherapy because the side effects aren’t worth it anymore,” she said. “The challenge for oncologists is not knowing in advance which patients will fall into each of these categories.”
She added that her geriatric oncology research focuses on improving risk stratification for older adults, such as those who are at least 70 with lung adenocarcinoma.
Oncologist Grant R. Williams, MD, MSPH, director of the Cancer & Aging Program at the University of Alabama at Birmingham, agreed in an interview that comprehensive geriatric assessments are important to guide treatment in the oldest adults. “In addition, it is important to elicit the goals of treatment as well,” he said. “For older adults that are fit or at least pre-frail and desire aggressive treatment, immunotherapy is a very reasonable approach, particularly when patients are closely monitored for side effects.”
No study funding is reported. The authors report no disclosures. Dr. Wong discloses an immediate family member is an employee and stock holder of Genentech. Dr. Williams has no disclosures.