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Safe to stop immunotherapy at 2 years in stable lung cancer
A new review of clinical trial data suggests that it is safe to stop immunotherapy after 2 years if the patient is progression free. There was no difference in overall survival between such patients and those who carried on with immunotherapy for another 2 years, so for 4 years in total.
“For patients who are progression free on immunotherapy for NSCLC, it is reasonable to stop therapy at 2 years, rather than continuing indefinitely,” said the investigators, led by medical oncologist Lova Sun, MD, a lung and head and neck cancer specialist at the University of Pennsylvania, Philadelphia.
“The lack of statistically significant overall survival advantage for” indefinite treatment “on adjusted analysis provides reassurance to patients and clinicians who wish to discontinue immunotherapy at 2 years,” they added.
The study was published online in JAMA Oncology to coincide with a presentation at the annual meeting of the American Society of Clinical Oncology.
Dr. Sun and colleagues commented that there have been a number of trials that have shown durable benefits persisting long after immunotherapy was stopped at 2 years, but clinicians seem to have been spooked into preferring indefinite treatment by a trial that showed worse survival with nivolumab when it was stopped at 1 year in responders versus ongoing treatment.
In an accompanying editorial, Jack West, MD, a medical oncologist and lung cancer specialist at City of Hope, Duarte, Calif., noted that given the “clear limitations in retrospective clinical data, we may want to wait for prospective randomized clinical trial data, but this will be a difficult study to complete, and results will take many years to become available.
“In the meantime, the perfect should not be the enemy of the good. These data may provide reassurance to us and patients that discontinuing treatment at 2 years can confer the same overall survival as extended treatment with lower risk of toxic effects, less time in treatment for patients, and considerably lower costs for our health care system,” he said.
Study details
For their review, Dr. Sun and colleagues included patients with advanced NSCLC called from 280 cancer clinics from across the United States.
The investigators compared overall survival in 113 advanced NSCLC patients treated with up-front immune checkpoint inhibitors (ICIs) for 700-760 days (that is, stopping within 2 years) with survival in 593 patients treated beyond 760 days (the indefinite therapy group).
Patients were diagnosed from 2016 to 2020 at a median age of 69 years and were about evenly split between the sexes. The team noted that although all the patients were progression free at 2 years, only about one in five discontinued ICIs, highlighting “a strong bias toward potential overtreatment [vs.] possible undertreatment,” as Dr. West put it in the editorial.
Approximately half of the patients in both groups were treated initially with immunotherapy alone and the rest in combination with chemotherapy.
The 2-year overall survival from the 760-day mark was 79% in the fixed-duration group versus 81% with indefinite treatment, with no difference on either univariate (hazard ratio, 1.26; P = .36) or multivariable (HR, 1.33; P = .29) analysis adjusting for smoking history, PD-L1 status, histology, and other covariates.
Eleven patients in the fixed-duration cohort (10%) subsequently had progression and were rechallenged with an ICI; all but one with the same ICI used frontline.
Median progression-free survival after rechallenge was 8.1 months, demonstrating that patients can still benefit from ICIs even after discontinuation, the investigators said.
The groups were well balanced except that patients in the fixed-duration group were more likely to be treated at an academic center and have a history of smoking, with a trend toward being more likely to have squamous cell carcinoma. “Even after adjusting for these covariates, there was no overall survival benefit for indefinite-duration therapy,” the team said.
There was no funding for the work. The investigators have numerous pharmaceutical industry ties, including Dr. Sun, who is a consultant for Regeneron, Genmab, Seagen, and Bayer, and disclosed funding from BluePrint Research, Seagen Research, and IO Biotech Research. Dr. West reported receiving personal fees from AstraZeneca, Genentech/Roche, Merck, and Regeneron.
A version of this article first appeared on Medscape.com.
A new review of clinical trial data suggests that it is safe to stop immunotherapy after 2 years if the patient is progression free. There was no difference in overall survival between such patients and those who carried on with immunotherapy for another 2 years, so for 4 years in total.
“For patients who are progression free on immunotherapy for NSCLC, it is reasonable to stop therapy at 2 years, rather than continuing indefinitely,” said the investigators, led by medical oncologist Lova Sun, MD, a lung and head and neck cancer specialist at the University of Pennsylvania, Philadelphia.
“The lack of statistically significant overall survival advantage for” indefinite treatment “on adjusted analysis provides reassurance to patients and clinicians who wish to discontinue immunotherapy at 2 years,” they added.
The study was published online in JAMA Oncology to coincide with a presentation at the annual meeting of the American Society of Clinical Oncology.
Dr. Sun and colleagues commented that there have been a number of trials that have shown durable benefits persisting long after immunotherapy was stopped at 2 years, but clinicians seem to have been spooked into preferring indefinite treatment by a trial that showed worse survival with nivolumab when it was stopped at 1 year in responders versus ongoing treatment.
In an accompanying editorial, Jack West, MD, a medical oncologist and lung cancer specialist at City of Hope, Duarte, Calif., noted that given the “clear limitations in retrospective clinical data, we may want to wait for prospective randomized clinical trial data, but this will be a difficult study to complete, and results will take many years to become available.
“In the meantime, the perfect should not be the enemy of the good. These data may provide reassurance to us and patients that discontinuing treatment at 2 years can confer the same overall survival as extended treatment with lower risk of toxic effects, less time in treatment for patients, and considerably lower costs for our health care system,” he said.
Study details
For their review, Dr. Sun and colleagues included patients with advanced NSCLC called from 280 cancer clinics from across the United States.
The investigators compared overall survival in 113 advanced NSCLC patients treated with up-front immune checkpoint inhibitors (ICIs) for 700-760 days (that is, stopping within 2 years) with survival in 593 patients treated beyond 760 days (the indefinite therapy group).
Patients were diagnosed from 2016 to 2020 at a median age of 69 years and were about evenly split between the sexes. The team noted that although all the patients were progression free at 2 years, only about one in five discontinued ICIs, highlighting “a strong bias toward potential overtreatment [vs.] possible undertreatment,” as Dr. West put it in the editorial.
Approximately half of the patients in both groups were treated initially with immunotherapy alone and the rest in combination with chemotherapy.
The 2-year overall survival from the 760-day mark was 79% in the fixed-duration group versus 81% with indefinite treatment, with no difference on either univariate (hazard ratio, 1.26; P = .36) or multivariable (HR, 1.33; P = .29) analysis adjusting for smoking history, PD-L1 status, histology, and other covariates.
Eleven patients in the fixed-duration cohort (10%) subsequently had progression and were rechallenged with an ICI; all but one with the same ICI used frontline.
Median progression-free survival after rechallenge was 8.1 months, demonstrating that patients can still benefit from ICIs even after discontinuation, the investigators said.
The groups were well balanced except that patients in the fixed-duration group were more likely to be treated at an academic center and have a history of smoking, with a trend toward being more likely to have squamous cell carcinoma. “Even after adjusting for these covariates, there was no overall survival benefit for indefinite-duration therapy,” the team said.
There was no funding for the work. The investigators have numerous pharmaceutical industry ties, including Dr. Sun, who is a consultant for Regeneron, Genmab, Seagen, and Bayer, and disclosed funding from BluePrint Research, Seagen Research, and IO Biotech Research. Dr. West reported receiving personal fees from AstraZeneca, Genentech/Roche, Merck, and Regeneron.
A version of this article first appeared on Medscape.com.
A new review of clinical trial data suggests that it is safe to stop immunotherapy after 2 years if the patient is progression free. There was no difference in overall survival between such patients and those who carried on with immunotherapy for another 2 years, so for 4 years in total.
“For patients who are progression free on immunotherapy for NSCLC, it is reasonable to stop therapy at 2 years, rather than continuing indefinitely,” said the investigators, led by medical oncologist Lova Sun, MD, a lung and head and neck cancer specialist at the University of Pennsylvania, Philadelphia.
“The lack of statistically significant overall survival advantage for” indefinite treatment “on adjusted analysis provides reassurance to patients and clinicians who wish to discontinue immunotherapy at 2 years,” they added.
The study was published online in JAMA Oncology to coincide with a presentation at the annual meeting of the American Society of Clinical Oncology.
Dr. Sun and colleagues commented that there have been a number of trials that have shown durable benefits persisting long after immunotherapy was stopped at 2 years, but clinicians seem to have been spooked into preferring indefinite treatment by a trial that showed worse survival with nivolumab when it was stopped at 1 year in responders versus ongoing treatment.
In an accompanying editorial, Jack West, MD, a medical oncologist and lung cancer specialist at City of Hope, Duarte, Calif., noted that given the “clear limitations in retrospective clinical data, we may want to wait for prospective randomized clinical trial data, but this will be a difficult study to complete, and results will take many years to become available.
“In the meantime, the perfect should not be the enemy of the good. These data may provide reassurance to us and patients that discontinuing treatment at 2 years can confer the same overall survival as extended treatment with lower risk of toxic effects, less time in treatment for patients, and considerably lower costs for our health care system,” he said.
Study details
For their review, Dr. Sun and colleagues included patients with advanced NSCLC called from 280 cancer clinics from across the United States.
The investigators compared overall survival in 113 advanced NSCLC patients treated with up-front immune checkpoint inhibitors (ICIs) for 700-760 days (that is, stopping within 2 years) with survival in 593 patients treated beyond 760 days (the indefinite therapy group).
Patients were diagnosed from 2016 to 2020 at a median age of 69 years and were about evenly split between the sexes. The team noted that although all the patients were progression free at 2 years, only about one in five discontinued ICIs, highlighting “a strong bias toward potential overtreatment [vs.] possible undertreatment,” as Dr. West put it in the editorial.
Approximately half of the patients in both groups were treated initially with immunotherapy alone and the rest in combination with chemotherapy.
The 2-year overall survival from the 760-day mark was 79% in the fixed-duration group versus 81% with indefinite treatment, with no difference on either univariate (hazard ratio, 1.26; P = .36) or multivariable (HR, 1.33; P = .29) analysis adjusting for smoking history, PD-L1 status, histology, and other covariates.
Eleven patients in the fixed-duration cohort (10%) subsequently had progression and were rechallenged with an ICI; all but one with the same ICI used frontline.
Median progression-free survival after rechallenge was 8.1 months, demonstrating that patients can still benefit from ICIs even after discontinuation, the investigators said.
The groups were well balanced except that patients in the fixed-duration group were more likely to be treated at an academic center and have a history of smoking, with a trend toward being more likely to have squamous cell carcinoma. “Even after adjusting for these covariates, there was no overall survival benefit for indefinite-duration therapy,” the team said.
There was no funding for the work. The investigators have numerous pharmaceutical industry ties, including Dr. Sun, who is a consultant for Regeneron, Genmab, Seagen, and Bayer, and disclosed funding from BluePrint Research, Seagen Research, and IO Biotech Research. Dr. West reported receiving personal fees from AstraZeneca, Genentech/Roche, Merck, and Regeneron.
A version of this article first appeared on Medscape.com.
FROM JAMA ONCOLOGY
SCLC: Bispecific antibody shows phase 1 promise
CHICAGO –
The antibody promotes the destruction of tumor cells by T cells by acting as a bridge between T cells and tumors.
SCLC has largely resisted efforts to identify unique surface markers. DLL3 is an exception: It is rarely expressed in normal cells, and it seems to be important to tumor biology, according to Martin Wermke, MD, who presented the study at the annual meeting of the American Society of Clinical Oncology.
A rare SCLC biomarker
“The problem, I think, is that small cell [lung cancer] with its high mutational burden is a bunch of many different subentities and you will probably not find a single driver mutation as you do in non–small cell lung cancer. So in that [way] it’s different in its biology,” said Dr. Wermke, professor of experimental tumor therapy at the National Center for Tumor Diseases in Dresden, Germany.
Nevertheless, DLL3 is a sensitive biomarker, with over 90% of SCLC tumors positive for the surface marker, according to Dr. Wermke. “It’s one of the first which proved to be a reliable [SCLC] biomarker for therapeutic approaches,” said Dr. Wermke.
This isn’t the first clinical experience with DLL3. An anti-DLL3 antibody was used as part of an antibody-drug conjugate called Rova-T, which failed a phase 3 trial in SCLC in 2021 and was subsequently canceled by AbbVie, but Dr. Wermke believes that the issue was with the drug and linker (a chemical tag that links the cytotoxic drug to the antibody, which is designed to release the drug in an appropriate environment such as the interior of a tumor cell after an antibody-drug conjugate has been internalized by the tumor cell), not DLL3. DLL3 is also being investigated as a component of chimeric antigen receptor T-cell therapy, though no clinical results have been reported, Dr. Wermke said.
Study methods and results
The study included 107 patients. The median age was 60.0 years, and 57% were male. To be included, patients had to have advanced SCLC, large cell neuroendocrine carcinoma, or extrapulmonary neuroendocrine carcinoma, as well as test positive for DLL3 expression.
The drug was well tolerated: 86% of patients experienced at least one treatment-related adverse event: 59% with a grade 1-2 TRAE and 27% with a grade 3-5 TRAE. Cytokine release syndrome (CRS) occurred in 59% of patients, but just 2% were grade 3-5. TRAEs led to discontinuation in 4% of patients. Physicians were able to manage CRS with supportive care, steroids, and anti–interleukin-6 receptor antibodies.
The treatment showed signs of efficacy, with partial responses occurring in 18% of patients, stable disease in 23%, progressive disease in 45%, while 13% were not evaluable.
At doses of 90 mg/kg or above, partial response occurred in 25% of patients, stable disease in 27%, and progressive disease in 31%, while 13% were not evaluable. Similar patterns were seen across three tumor types.
Of 18 responders, 14 continued to be responders at the time of the presentation. The longest response lengths were 13.1 months, 10.7 months, and 9.4 months.
Dr. Wermke said that the responses were encouraging, particularly the duration of some responses.
“Having a small cell [lung cancer] patient responding to something for more than a year is extraordinary. It comes with side effects, which are usually seen during the first [doses]. After that, the drug is pretty well tolerable, and that is also something which distinguishes it from alternative second-line approaches,” he said.
Well tolerated, but take efficacy data with a grain of salt
The study was encouraging but should be treated with caution, according to Vamsidhar Velcheti, MD, who moderated the session where the research was presented.
“The toxicity profile is actually very promising and it’s still very early, but there’s certainly a lot of interest in DLL3-targeted [therapies]. We’ve seen some very exciting data with other assets in this category as well,” said Dr. Velcheti, director of thoracic oncology at NYU Langone Health, New York.
Phase 1 efficacy data can be tantalizing but often fails to hold up to further testing, according to Dr. Velcheti. “We’ve seen signals in phase 1 data before, and we’ve been burned. We saw really promising data with Rova-T, and the confirmatory trials were negative, – so we want to be cautiously optimistic,” said Dr. Velcheti.
He also pointed out that patient selection will be important for such studies, considering that SCLC patients often have a lot of comorbidities and the therapy’s potential for causing CRS.
Both Dr. Wermke and Dr. Velcheti have received funding from numerous pharmaceutical companies. Dr. Wermke has consulted with or advised with Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, ImCheck Therapeutics, Immatics, ISA Pharmaceuticals, Lilly, and Novartis.
CHICAGO –
The antibody promotes the destruction of tumor cells by T cells by acting as a bridge between T cells and tumors.
SCLC has largely resisted efforts to identify unique surface markers. DLL3 is an exception: It is rarely expressed in normal cells, and it seems to be important to tumor biology, according to Martin Wermke, MD, who presented the study at the annual meeting of the American Society of Clinical Oncology.
A rare SCLC biomarker
“The problem, I think, is that small cell [lung cancer] with its high mutational burden is a bunch of many different subentities and you will probably not find a single driver mutation as you do in non–small cell lung cancer. So in that [way] it’s different in its biology,” said Dr. Wermke, professor of experimental tumor therapy at the National Center for Tumor Diseases in Dresden, Germany.
Nevertheless, DLL3 is a sensitive biomarker, with over 90% of SCLC tumors positive for the surface marker, according to Dr. Wermke. “It’s one of the first which proved to be a reliable [SCLC] biomarker for therapeutic approaches,” said Dr. Wermke.
This isn’t the first clinical experience with DLL3. An anti-DLL3 antibody was used as part of an antibody-drug conjugate called Rova-T, which failed a phase 3 trial in SCLC in 2021 and was subsequently canceled by AbbVie, but Dr. Wermke believes that the issue was with the drug and linker (a chemical tag that links the cytotoxic drug to the antibody, which is designed to release the drug in an appropriate environment such as the interior of a tumor cell after an antibody-drug conjugate has been internalized by the tumor cell), not DLL3. DLL3 is also being investigated as a component of chimeric antigen receptor T-cell therapy, though no clinical results have been reported, Dr. Wermke said.
Study methods and results
The study included 107 patients. The median age was 60.0 years, and 57% were male. To be included, patients had to have advanced SCLC, large cell neuroendocrine carcinoma, or extrapulmonary neuroendocrine carcinoma, as well as test positive for DLL3 expression.
The drug was well tolerated: 86% of patients experienced at least one treatment-related adverse event: 59% with a grade 1-2 TRAE and 27% with a grade 3-5 TRAE. Cytokine release syndrome (CRS) occurred in 59% of patients, but just 2% were grade 3-5. TRAEs led to discontinuation in 4% of patients. Physicians were able to manage CRS with supportive care, steroids, and anti–interleukin-6 receptor antibodies.
The treatment showed signs of efficacy, with partial responses occurring in 18% of patients, stable disease in 23%, progressive disease in 45%, while 13% were not evaluable.
At doses of 90 mg/kg or above, partial response occurred in 25% of patients, stable disease in 27%, and progressive disease in 31%, while 13% were not evaluable. Similar patterns were seen across three tumor types.
Of 18 responders, 14 continued to be responders at the time of the presentation. The longest response lengths were 13.1 months, 10.7 months, and 9.4 months.
Dr. Wermke said that the responses were encouraging, particularly the duration of some responses.
“Having a small cell [lung cancer] patient responding to something for more than a year is extraordinary. It comes with side effects, which are usually seen during the first [doses]. After that, the drug is pretty well tolerable, and that is also something which distinguishes it from alternative second-line approaches,” he said.
Well tolerated, but take efficacy data with a grain of salt
The study was encouraging but should be treated with caution, according to Vamsidhar Velcheti, MD, who moderated the session where the research was presented.
“The toxicity profile is actually very promising and it’s still very early, but there’s certainly a lot of interest in DLL3-targeted [therapies]. We’ve seen some very exciting data with other assets in this category as well,” said Dr. Velcheti, director of thoracic oncology at NYU Langone Health, New York.
Phase 1 efficacy data can be tantalizing but often fails to hold up to further testing, according to Dr. Velcheti. “We’ve seen signals in phase 1 data before, and we’ve been burned. We saw really promising data with Rova-T, and the confirmatory trials were negative, – so we want to be cautiously optimistic,” said Dr. Velcheti.
He also pointed out that patient selection will be important for such studies, considering that SCLC patients often have a lot of comorbidities and the therapy’s potential for causing CRS.
Both Dr. Wermke and Dr. Velcheti have received funding from numerous pharmaceutical companies. Dr. Wermke has consulted with or advised with Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, ImCheck Therapeutics, Immatics, ISA Pharmaceuticals, Lilly, and Novartis.
CHICAGO –
The antibody promotes the destruction of tumor cells by T cells by acting as a bridge between T cells and tumors.
SCLC has largely resisted efforts to identify unique surface markers. DLL3 is an exception: It is rarely expressed in normal cells, and it seems to be important to tumor biology, according to Martin Wermke, MD, who presented the study at the annual meeting of the American Society of Clinical Oncology.
A rare SCLC biomarker
“The problem, I think, is that small cell [lung cancer] with its high mutational burden is a bunch of many different subentities and you will probably not find a single driver mutation as you do in non–small cell lung cancer. So in that [way] it’s different in its biology,” said Dr. Wermke, professor of experimental tumor therapy at the National Center for Tumor Diseases in Dresden, Germany.
Nevertheless, DLL3 is a sensitive biomarker, with over 90% of SCLC tumors positive for the surface marker, according to Dr. Wermke. “It’s one of the first which proved to be a reliable [SCLC] biomarker for therapeutic approaches,” said Dr. Wermke.
This isn’t the first clinical experience with DLL3. An anti-DLL3 antibody was used as part of an antibody-drug conjugate called Rova-T, which failed a phase 3 trial in SCLC in 2021 and was subsequently canceled by AbbVie, but Dr. Wermke believes that the issue was with the drug and linker (a chemical tag that links the cytotoxic drug to the antibody, which is designed to release the drug in an appropriate environment such as the interior of a tumor cell after an antibody-drug conjugate has been internalized by the tumor cell), not DLL3. DLL3 is also being investigated as a component of chimeric antigen receptor T-cell therapy, though no clinical results have been reported, Dr. Wermke said.
Study methods and results
The study included 107 patients. The median age was 60.0 years, and 57% were male. To be included, patients had to have advanced SCLC, large cell neuroendocrine carcinoma, or extrapulmonary neuroendocrine carcinoma, as well as test positive for DLL3 expression.
The drug was well tolerated: 86% of patients experienced at least one treatment-related adverse event: 59% with a grade 1-2 TRAE and 27% with a grade 3-5 TRAE. Cytokine release syndrome (CRS) occurred in 59% of patients, but just 2% were grade 3-5. TRAEs led to discontinuation in 4% of patients. Physicians were able to manage CRS with supportive care, steroids, and anti–interleukin-6 receptor antibodies.
The treatment showed signs of efficacy, with partial responses occurring in 18% of patients, stable disease in 23%, progressive disease in 45%, while 13% were not evaluable.
At doses of 90 mg/kg or above, partial response occurred in 25% of patients, stable disease in 27%, and progressive disease in 31%, while 13% were not evaluable. Similar patterns were seen across three tumor types.
Of 18 responders, 14 continued to be responders at the time of the presentation. The longest response lengths were 13.1 months, 10.7 months, and 9.4 months.
Dr. Wermke said that the responses were encouraging, particularly the duration of some responses.
“Having a small cell [lung cancer] patient responding to something for more than a year is extraordinary. It comes with side effects, which are usually seen during the first [doses]. After that, the drug is pretty well tolerable, and that is also something which distinguishes it from alternative second-line approaches,” he said.
Well tolerated, but take efficacy data with a grain of salt
The study was encouraging but should be treated with caution, according to Vamsidhar Velcheti, MD, who moderated the session where the research was presented.
“The toxicity profile is actually very promising and it’s still very early, but there’s certainly a lot of interest in DLL3-targeted [therapies]. We’ve seen some very exciting data with other assets in this category as well,” said Dr. Velcheti, director of thoracic oncology at NYU Langone Health, New York.
Phase 1 efficacy data can be tantalizing but often fails to hold up to further testing, according to Dr. Velcheti. “We’ve seen signals in phase 1 data before, and we’ve been burned. We saw really promising data with Rova-T, and the confirmatory trials were negative, – so we want to be cautiously optimistic,” said Dr. Velcheti.
He also pointed out that patient selection will be important for such studies, considering that SCLC patients often have a lot of comorbidities and the therapy’s potential for causing CRS.
Both Dr. Wermke and Dr. Velcheti have received funding from numerous pharmaceutical companies. Dr. Wermke has consulted with or advised with Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, ImCheck Therapeutics, Immatics, ISA Pharmaceuticals, Lilly, and Novartis.
AT ASCO 2023
Warning on use of sotorasib after ICI in lung cancer
because of the risk of increased toxicity.
Sotorasib is indicated for adults with locally advanced or metastatic NSCLC who carry a KRASG12C mutation, which occurs in about 13% of cases.
Since its approval in 2021, sotorasib has emerged as “a new standard of care” for such patients after chemotherapy and anti–PD-L1 failure, the investigators say.
The new warning comes after the team compared 48 patients who received an anti–PD-L1 – most often pembrolizumab alone or in combination with platinum-based chemotherapy – before sotorasib with a control group of 54 patients who either didn’t receive an anti–PD-L1 before sotorasib or had at least one other treatment in between.
The team found that sequential anti–PD-L1 and sotorasib therapy significantly increased the risk of severe sotorasib-related hepatotoxicity and also the risk of non-liver adverse events, typically in patients who received sotorasib within 30 days of an anti–PD-L1.
“We suggest avoiding starting sotorasib within 30 days from the last anti–PD-(L)1 infusion,” say senior author Michaël Duruisseaux, MD, PhD, Louis Pradel Hospital, Bron, France, and collegues.
The findings should also “prompt a close monitoring for the development of hepatotoxicity and non-liver AEs [in] patients who receive sotorasib after anti–PD-(L)1,” they add.
The study was published in the Journal of Thoracic Oncology.
Actionable findings
“I consider the results to be highly credible and informative to my own practice,” said Jack West, MD, a thoracic medical oncologist at the City of Hope outside of Los Angeles, said in an interview.
The findings “may lead me to favor a trial of docetaxel as an intervening therapy for patients who have very recently discontinued immunotherapy, deferring sotorasib at least a few weeks and ideally several months,” Dr. West commented. “I think this is a particularly reasonable approach when we remember that sotorasib conferred no improvement in overall survival at all over docetaxel in the CodeBreaK 200 trial in KRASG12C-mutated NSCLC.”
Overall, the study “corroborates what we’ve seen in the limited first-line experience of sotorasib combined with immunotherapy and also echoes our experience of other targeted therapies, such as osimertinib administered in the weeks just after patients received immunotherapy, which is known to be associated with life-threatening pneumonitis,” he said.
Jared Weiss, MD, a thoracic medical oncologist at the University of North Carolina, Chapel Hill, said that given the long half-life of immune checkpoint inhibitors, “it is quite understandable that the toxicity challenges we previously saw with concurrent administration of immunotherapy and certain targeted therapies would be recapitulated in patients who had a relatively short interval between prior checkpoint inhibitor therapy and sotorasib.”
Even so, because of the aggressiveness of NSCLC, long treatment delays between immunotherapy and sotorasib therapy are “not a favored option.”
Like Dr. West, Dr. Weiss said docetaxel (with or without ramucirumab) is a sound intervening alternative.
Another option is to use adagrasib in the second line instead of sotorasib, Dr. Weiss suggested. It’s also a KRASG12C inhibitor but hasn’t so far been associated with severe hepatotoxicity, he said.
Hossein Borghaei, DO, a thoracic medical oncologist at Fox Chase Cancer Center, Philadelphia, agrees with his colleagues and thinks that what the French team found “is real.”
As the investigators suggest, “it might be that sotorasib leads to an inflammatory microenvironment that causes hepatotoxicity in the presence of a checkpoint inhibitor. In that case,” a lower dose of sotorasib might help reduce toxicity while remaining effective, Dr. Broghaei suggested.
Study details
The French team was prompted to investigate the issue by a report of life-threatening hepatitis in a patient with NSCLC for whom sotorasib therapy was initiated 14 weeks after treatment with pembrolizumab, as well as by “the long story of adverse events ... observed with sequential use of [immune checkpoint inhibitors] and targeted therapy.”
Like Dr. Weiss, they note that severe hepatotoxicity after anti–PD-L1 therapy has not, to date, been reported for other KRASG12C inhibitors.
Patients in the study were treated outside of clinical trials at 16 medical centers in France.
Half of the patients (24/48) who were treated immediately with an anti–PD-L1 after sotorasib therapy developed grade 3 or higher sotorasib-related adverse events, including 16 (33%) with severe sotorasib-related hepatotoxicity. Severe diarrhea and fatigue were also more frequent with sequential therapy.
Severe events typically occurred within 30 days of the last anti–PD-L1 infusion and to a lesser extent within 31-60 days.
In the control arm, the rate of severe sotorasib-related adverse events was 13% (7/54). Six patients (11%) experienced severe hepatotoxicity. There was one sotorasib-related death in the sequential therapy arm, which was due to toxic epidermal necrosis. No deaths occurred in the control group.
The two groups were balanced with respect to history of daily alcohol consumption and the presence of liver metastasis. More patients in the control arm had a history of hepatobiliary disease.
The study received no outside funding. Many of the authors report ties with pharmaceutical companies, including to Amgen, the maker of sotorasib, and Mirati Therapeutics, the maker of adagrasib. Dr. Weiss was an adagrasib investigator for Mirati. Dr. West is a regular contribiutor to Medscape and is an adviser for Amgen and Mirati as well as a speaker for Amgen. Dr. Borghaei reported extensive company ties. He has received research support, travel funding, and consulting fees from Amgen as well as consulting fees from Mirati.
A version of this article first appeared on Medscape.com.
because of the risk of increased toxicity.
Sotorasib is indicated for adults with locally advanced or metastatic NSCLC who carry a KRASG12C mutation, which occurs in about 13% of cases.
Since its approval in 2021, sotorasib has emerged as “a new standard of care” for such patients after chemotherapy and anti–PD-L1 failure, the investigators say.
The new warning comes after the team compared 48 patients who received an anti–PD-L1 – most often pembrolizumab alone or in combination with platinum-based chemotherapy – before sotorasib with a control group of 54 patients who either didn’t receive an anti–PD-L1 before sotorasib or had at least one other treatment in between.
The team found that sequential anti–PD-L1 and sotorasib therapy significantly increased the risk of severe sotorasib-related hepatotoxicity and also the risk of non-liver adverse events, typically in patients who received sotorasib within 30 days of an anti–PD-L1.
“We suggest avoiding starting sotorasib within 30 days from the last anti–PD-(L)1 infusion,” say senior author Michaël Duruisseaux, MD, PhD, Louis Pradel Hospital, Bron, France, and collegues.
The findings should also “prompt a close monitoring for the development of hepatotoxicity and non-liver AEs [in] patients who receive sotorasib after anti–PD-(L)1,” they add.
The study was published in the Journal of Thoracic Oncology.
Actionable findings
“I consider the results to be highly credible and informative to my own practice,” said Jack West, MD, a thoracic medical oncologist at the City of Hope outside of Los Angeles, said in an interview.
The findings “may lead me to favor a trial of docetaxel as an intervening therapy for patients who have very recently discontinued immunotherapy, deferring sotorasib at least a few weeks and ideally several months,” Dr. West commented. “I think this is a particularly reasonable approach when we remember that sotorasib conferred no improvement in overall survival at all over docetaxel in the CodeBreaK 200 trial in KRASG12C-mutated NSCLC.”
Overall, the study “corroborates what we’ve seen in the limited first-line experience of sotorasib combined with immunotherapy and also echoes our experience of other targeted therapies, such as osimertinib administered in the weeks just after patients received immunotherapy, which is known to be associated with life-threatening pneumonitis,” he said.
Jared Weiss, MD, a thoracic medical oncologist at the University of North Carolina, Chapel Hill, said that given the long half-life of immune checkpoint inhibitors, “it is quite understandable that the toxicity challenges we previously saw with concurrent administration of immunotherapy and certain targeted therapies would be recapitulated in patients who had a relatively short interval between prior checkpoint inhibitor therapy and sotorasib.”
Even so, because of the aggressiveness of NSCLC, long treatment delays between immunotherapy and sotorasib therapy are “not a favored option.”
Like Dr. West, Dr. Weiss said docetaxel (with or without ramucirumab) is a sound intervening alternative.
Another option is to use adagrasib in the second line instead of sotorasib, Dr. Weiss suggested. It’s also a KRASG12C inhibitor but hasn’t so far been associated with severe hepatotoxicity, he said.
Hossein Borghaei, DO, a thoracic medical oncologist at Fox Chase Cancer Center, Philadelphia, agrees with his colleagues and thinks that what the French team found “is real.”
As the investigators suggest, “it might be that sotorasib leads to an inflammatory microenvironment that causes hepatotoxicity in the presence of a checkpoint inhibitor. In that case,” a lower dose of sotorasib might help reduce toxicity while remaining effective, Dr. Broghaei suggested.
Study details
The French team was prompted to investigate the issue by a report of life-threatening hepatitis in a patient with NSCLC for whom sotorasib therapy was initiated 14 weeks after treatment with pembrolizumab, as well as by “the long story of adverse events ... observed with sequential use of [immune checkpoint inhibitors] and targeted therapy.”
Like Dr. Weiss, they note that severe hepatotoxicity after anti–PD-L1 therapy has not, to date, been reported for other KRASG12C inhibitors.
Patients in the study were treated outside of clinical trials at 16 medical centers in France.
Half of the patients (24/48) who were treated immediately with an anti–PD-L1 after sotorasib therapy developed grade 3 or higher sotorasib-related adverse events, including 16 (33%) with severe sotorasib-related hepatotoxicity. Severe diarrhea and fatigue were also more frequent with sequential therapy.
Severe events typically occurred within 30 days of the last anti–PD-L1 infusion and to a lesser extent within 31-60 days.
In the control arm, the rate of severe sotorasib-related adverse events was 13% (7/54). Six patients (11%) experienced severe hepatotoxicity. There was one sotorasib-related death in the sequential therapy arm, which was due to toxic epidermal necrosis. No deaths occurred in the control group.
The two groups were balanced with respect to history of daily alcohol consumption and the presence of liver metastasis. More patients in the control arm had a history of hepatobiliary disease.
The study received no outside funding. Many of the authors report ties with pharmaceutical companies, including to Amgen, the maker of sotorasib, and Mirati Therapeutics, the maker of adagrasib. Dr. Weiss was an adagrasib investigator for Mirati. Dr. West is a regular contribiutor to Medscape and is an adviser for Amgen and Mirati as well as a speaker for Amgen. Dr. Borghaei reported extensive company ties. He has received research support, travel funding, and consulting fees from Amgen as well as consulting fees from Mirati.
A version of this article first appeared on Medscape.com.
because of the risk of increased toxicity.
Sotorasib is indicated for adults with locally advanced or metastatic NSCLC who carry a KRASG12C mutation, which occurs in about 13% of cases.
Since its approval in 2021, sotorasib has emerged as “a new standard of care” for such patients after chemotherapy and anti–PD-L1 failure, the investigators say.
The new warning comes after the team compared 48 patients who received an anti–PD-L1 – most often pembrolizumab alone or in combination with platinum-based chemotherapy – before sotorasib with a control group of 54 patients who either didn’t receive an anti–PD-L1 before sotorasib or had at least one other treatment in between.
The team found that sequential anti–PD-L1 and sotorasib therapy significantly increased the risk of severe sotorasib-related hepatotoxicity and also the risk of non-liver adverse events, typically in patients who received sotorasib within 30 days of an anti–PD-L1.
“We suggest avoiding starting sotorasib within 30 days from the last anti–PD-(L)1 infusion,” say senior author Michaël Duruisseaux, MD, PhD, Louis Pradel Hospital, Bron, France, and collegues.
The findings should also “prompt a close monitoring for the development of hepatotoxicity and non-liver AEs [in] patients who receive sotorasib after anti–PD-(L)1,” they add.
The study was published in the Journal of Thoracic Oncology.
Actionable findings
“I consider the results to be highly credible and informative to my own practice,” said Jack West, MD, a thoracic medical oncologist at the City of Hope outside of Los Angeles, said in an interview.
The findings “may lead me to favor a trial of docetaxel as an intervening therapy for patients who have very recently discontinued immunotherapy, deferring sotorasib at least a few weeks and ideally several months,” Dr. West commented. “I think this is a particularly reasonable approach when we remember that sotorasib conferred no improvement in overall survival at all over docetaxel in the CodeBreaK 200 trial in KRASG12C-mutated NSCLC.”
Overall, the study “corroborates what we’ve seen in the limited first-line experience of sotorasib combined with immunotherapy and also echoes our experience of other targeted therapies, such as osimertinib administered in the weeks just after patients received immunotherapy, which is known to be associated with life-threatening pneumonitis,” he said.
Jared Weiss, MD, a thoracic medical oncologist at the University of North Carolina, Chapel Hill, said that given the long half-life of immune checkpoint inhibitors, “it is quite understandable that the toxicity challenges we previously saw with concurrent administration of immunotherapy and certain targeted therapies would be recapitulated in patients who had a relatively short interval between prior checkpoint inhibitor therapy and sotorasib.”
Even so, because of the aggressiveness of NSCLC, long treatment delays between immunotherapy and sotorasib therapy are “not a favored option.”
Like Dr. West, Dr. Weiss said docetaxel (with or without ramucirumab) is a sound intervening alternative.
Another option is to use adagrasib in the second line instead of sotorasib, Dr. Weiss suggested. It’s also a KRASG12C inhibitor but hasn’t so far been associated with severe hepatotoxicity, he said.
Hossein Borghaei, DO, a thoracic medical oncologist at Fox Chase Cancer Center, Philadelphia, agrees with his colleagues and thinks that what the French team found “is real.”
As the investigators suggest, “it might be that sotorasib leads to an inflammatory microenvironment that causes hepatotoxicity in the presence of a checkpoint inhibitor. In that case,” a lower dose of sotorasib might help reduce toxicity while remaining effective, Dr. Broghaei suggested.
Study details
The French team was prompted to investigate the issue by a report of life-threatening hepatitis in a patient with NSCLC for whom sotorasib therapy was initiated 14 weeks after treatment with pembrolizumab, as well as by “the long story of adverse events ... observed with sequential use of [immune checkpoint inhibitors] and targeted therapy.”
Like Dr. Weiss, they note that severe hepatotoxicity after anti–PD-L1 therapy has not, to date, been reported for other KRASG12C inhibitors.
Patients in the study were treated outside of clinical trials at 16 medical centers in France.
Half of the patients (24/48) who were treated immediately with an anti–PD-L1 after sotorasib therapy developed grade 3 or higher sotorasib-related adverse events, including 16 (33%) with severe sotorasib-related hepatotoxicity. Severe diarrhea and fatigue were also more frequent with sequential therapy.
Severe events typically occurred within 30 days of the last anti–PD-L1 infusion and to a lesser extent within 31-60 days.
In the control arm, the rate of severe sotorasib-related adverse events was 13% (7/54). Six patients (11%) experienced severe hepatotoxicity. There was one sotorasib-related death in the sequential therapy arm, which was due to toxic epidermal necrosis. No deaths occurred in the control group.
The two groups were balanced with respect to history of daily alcohol consumption and the presence of liver metastasis. More patients in the control arm had a history of hepatobiliary disease.
The study received no outside funding. Many of the authors report ties with pharmaceutical companies, including to Amgen, the maker of sotorasib, and Mirati Therapeutics, the maker of adagrasib. Dr. Weiss was an adagrasib investigator for Mirati. Dr. West is a regular contribiutor to Medscape and is an adviser for Amgen and Mirati as well as a speaker for Amgen. Dr. Borghaei reported extensive company ties. He has received research support, travel funding, and consulting fees from Amgen as well as consulting fees from Mirati.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THORACIC ONCOLOGY
Immunotherapy plus chemo improves quality of life in NSCLC
In the trial, patients who received the PD-1 inhibitor plus platinum-doublet chemotherapy in the first-line setting reported significant improvements in pain symptoms and delay in time to deterioration, as well as improvements in disease-related symptoms, such as dyspnea, constipation, nausea, and vomiting.
Overall, “the findings support the concept that the superior efficacy and favorable safety profile of cemiplimab plus chemotherapy translate to better patient-reported outcomes compared with chemotherapy alone in patients with advanced non–small cell lung cancer, “ corresponding author Tamta Makharadze, MD, of LTD High Technology Hospital Med Center in Batumi, Georgia, said in a press release.
The delays reported in time to definitive clinically meaningful deterioration “are particularly pertinent, given the anticipated continued improvements in cancer survivorship among patients with advanced NSCLC,” the authors explained.
The research was published online May 8 in Cancer.
Quality of life is especially important for patients with advanced NSCLC, for whom the benefits of improved survival must be weighed against the potential drawbacks of treatment toxicities, which can severely impact quality of life, the authors noted.
In the initial multinational phase 3 EMPOWER-Lung 3 trial, Dr. Makharadze and colleagues randomly assigned 466 patients with stage IIIB, IIIC, or stage IV NSCLC to receive either 350 mg of cemiplimab (Libtayo, Regeneron Pharmaceuticals) every 3 weeks along with investigator’s choice of platinum‐doublet chemotherapy or placebo plus chemotherapy. Investigator’s choice of chemotherapy was either paclitaxel plus carboplatin or cisplatin, pemetrexed plus carboplatin, or cisplatin.
The researchers found that the addition of cemiplimab to chemotherapy was associated with a significant, almost 9-month improvement in overall survival. While the trial also highlighted significant improvements in quality of life, functioning, and most symptoms with cemiplimab in comparison with placebo, the current study provides more details on these patient-reported quality-of-life outcomes.
In the latest analysis, Dr. Makharadze and colleagues evaluated data on the 312 patients in the cemiplimab arm and the 154 in the placebo arm. The median age of the patients was 63 years, and most (83.9%) were men.
Patients in the cemiplimab arm reported significant improvements in pain symptoms from baseline, as measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life–Core 30 (QLQ‐C30) score (–4.98; P = .004).
Patients who were treated with cemiplimab also reported a significant delay in time to definitive clinically meaningful deterioration (hazard ratio [HR], 0.39; P < .0001).
Significant delays in the time to deterioration in other functioning and symptom scales favored the cemiplimab group, including dyspnea (HR, 0.54), nausea/vomiting (HR, 0.39), and constipation (HR, 0.48).
The cemiplimab group also reported significantly delayed time to deterioration in physical (HR, 0.62) and emotional functioning (HR, 0.52) compared with the placebo arm as well as significant overall improvements from baseline in global health status/quality of life scores.
No significant improvements in patient-reported outcomes favoring the placebo group were observed on any quality-of-life metric evaluated using the symptom scales.
As for study limitations, the authors said that although about 86% of patients in both arms completed at least one question at baseline and post baseline, “the results may have overrepresented the patients who did well in both treatment arms because patients who progressed no longer completed the questionnaires.”
Nevertheless, the results “show that the favorable efficacy achieved with cemiplimab plus chemotherapy over placebo plus chemotherapy is accompanied by significant overall improvement in pain and significant delay in [time to definitive clinically meaningful deterioration] in multiple patient‐reported cancer‐related and lung cancer–specific functions and symptoms,” the authors concluded.
The study was sponsored by Regeneron Pharmaceuticals and Sanofi.
A version of this article originally appeared on Medscape.com.
In the trial, patients who received the PD-1 inhibitor plus platinum-doublet chemotherapy in the first-line setting reported significant improvements in pain symptoms and delay in time to deterioration, as well as improvements in disease-related symptoms, such as dyspnea, constipation, nausea, and vomiting.
Overall, “the findings support the concept that the superior efficacy and favorable safety profile of cemiplimab plus chemotherapy translate to better patient-reported outcomes compared with chemotherapy alone in patients with advanced non–small cell lung cancer, “ corresponding author Tamta Makharadze, MD, of LTD High Technology Hospital Med Center in Batumi, Georgia, said in a press release.
The delays reported in time to definitive clinically meaningful deterioration “are particularly pertinent, given the anticipated continued improvements in cancer survivorship among patients with advanced NSCLC,” the authors explained.
The research was published online May 8 in Cancer.
Quality of life is especially important for patients with advanced NSCLC, for whom the benefits of improved survival must be weighed against the potential drawbacks of treatment toxicities, which can severely impact quality of life, the authors noted.
In the initial multinational phase 3 EMPOWER-Lung 3 trial, Dr. Makharadze and colleagues randomly assigned 466 patients with stage IIIB, IIIC, or stage IV NSCLC to receive either 350 mg of cemiplimab (Libtayo, Regeneron Pharmaceuticals) every 3 weeks along with investigator’s choice of platinum‐doublet chemotherapy or placebo plus chemotherapy. Investigator’s choice of chemotherapy was either paclitaxel plus carboplatin or cisplatin, pemetrexed plus carboplatin, or cisplatin.
The researchers found that the addition of cemiplimab to chemotherapy was associated with a significant, almost 9-month improvement in overall survival. While the trial also highlighted significant improvements in quality of life, functioning, and most symptoms with cemiplimab in comparison with placebo, the current study provides more details on these patient-reported quality-of-life outcomes.
In the latest analysis, Dr. Makharadze and colleagues evaluated data on the 312 patients in the cemiplimab arm and the 154 in the placebo arm. The median age of the patients was 63 years, and most (83.9%) were men.
Patients in the cemiplimab arm reported significant improvements in pain symptoms from baseline, as measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life–Core 30 (QLQ‐C30) score (–4.98; P = .004).
Patients who were treated with cemiplimab also reported a significant delay in time to definitive clinically meaningful deterioration (hazard ratio [HR], 0.39; P < .0001).
Significant delays in the time to deterioration in other functioning and symptom scales favored the cemiplimab group, including dyspnea (HR, 0.54), nausea/vomiting (HR, 0.39), and constipation (HR, 0.48).
The cemiplimab group also reported significantly delayed time to deterioration in physical (HR, 0.62) and emotional functioning (HR, 0.52) compared with the placebo arm as well as significant overall improvements from baseline in global health status/quality of life scores.
No significant improvements in patient-reported outcomes favoring the placebo group were observed on any quality-of-life metric evaluated using the symptom scales.
As for study limitations, the authors said that although about 86% of patients in both arms completed at least one question at baseline and post baseline, “the results may have overrepresented the patients who did well in both treatment arms because patients who progressed no longer completed the questionnaires.”
Nevertheless, the results “show that the favorable efficacy achieved with cemiplimab plus chemotherapy over placebo plus chemotherapy is accompanied by significant overall improvement in pain and significant delay in [time to definitive clinically meaningful deterioration] in multiple patient‐reported cancer‐related and lung cancer–specific functions and symptoms,” the authors concluded.
The study was sponsored by Regeneron Pharmaceuticals and Sanofi.
A version of this article originally appeared on Medscape.com.
In the trial, patients who received the PD-1 inhibitor plus platinum-doublet chemotherapy in the first-line setting reported significant improvements in pain symptoms and delay in time to deterioration, as well as improvements in disease-related symptoms, such as dyspnea, constipation, nausea, and vomiting.
Overall, “the findings support the concept that the superior efficacy and favorable safety profile of cemiplimab plus chemotherapy translate to better patient-reported outcomes compared with chemotherapy alone in patients with advanced non–small cell lung cancer, “ corresponding author Tamta Makharadze, MD, of LTD High Technology Hospital Med Center in Batumi, Georgia, said in a press release.
The delays reported in time to definitive clinically meaningful deterioration “are particularly pertinent, given the anticipated continued improvements in cancer survivorship among patients with advanced NSCLC,” the authors explained.
The research was published online May 8 in Cancer.
Quality of life is especially important for patients with advanced NSCLC, for whom the benefits of improved survival must be weighed against the potential drawbacks of treatment toxicities, which can severely impact quality of life, the authors noted.
In the initial multinational phase 3 EMPOWER-Lung 3 trial, Dr. Makharadze and colleagues randomly assigned 466 patients with stage IIIB, IIIC, or stage IV NSCLC to receive either 350 mg of cemiplimab (Libtayo, Regeneron Pharmaceuticals) every 3 weeks along with investigator’s choice of platinum‐doublet chemotherapy or placebo plus chemotherapy. Investigator’s choice of chemotherapy was either paclitaxel plus carboplatin or cisplatin, pemetrexed plus carboplatin, or cisplatin.
The researchers found that the addition of cemiplimab to chemotherapy was associated with a significant, almost 9-month improvement in overall survival. While the trial also highlighted significant improvements in quality of life, functioning, and most symptoms with cemiplimab in comparison with placebo, the current study provides more details on these patient-reported quality-of-life outcomes.
In the latest analysis, Dr. Makharadze and colleagues evaluated data on the 312 patients in the cemiplimab arm and the 154 in the placebo arm. The median age of the patients was 63 years, and most (83.9%) were men.
Patients in the cemiplimab arm reported significant improvements in pain symptoms from baseline, as measured with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life–Core 30 (QLQ‐C30) score (–4.98; P = .004).
Patients who were treated with cemiplimab also reported a significant delay in time to definitive clinically meaningful deterioration (hazard ratio [HR], 0.39; P < .0001).
Significant delays in the time to deterioration in other functioning and symptom scales favored the cemiplimab group, including dyspnea (HR, 0.54), nausea/vomiting (HR, 0.39), and constipation (HR, 0.48).
The cemiplimab group also reported significantly delayed time to deterioration in physical (HR, 0.62) and emotional functioning (HR, 0.52) compared with the placebo arm as well as significant overall improvements from baseline in global health status/quality of life scores.
No significant improvements in patient-reported outcomes favoring the placebo group were observed on any quality-of-life metric evaluated using the symptom scales.
As for study limitations, the authors said that although about 86% of patients in both arms completed at least one question at baseline and post baseline, “the results may have overrepresented the patients who did well in both treatment arms because patients who progressed no longer completed the questionnaires.”
Nevertheless, the results “show that the favorable efficacy achieved with cemiplimab plus chemotherapy over placebo plus chemotherapy is accompanied by significant overall improvement in pain and significant delay in [time to definitive clinically meaningful deterioration] in multiple patient‐reported cancer‐related and lung cancer–specific functions and symptoms,” the authors concluded.
The study was sponsored by Regeneron Pharmaceuticals and Sanofi.
A version of this article originally appeared on Medscape.com.
FROM CANCER
Number of cancer survivors with functional limitations doubled in 20 years
Vishal Patel, BS, a student at the Dell Medical School at The University of Texas at Austin, and colleagues identified 51,258 cancer survivors from the National Health Interview Survey, representing a weighted population of approximately 178.8 million from 1999 to 2018.
Most survivors were women (60.2%) and were at least 65 years old (55.4%). In 1999, 3.6 million weighted survivors reported functional limitation. In 2018, the number increased to 8.2 million, a 2.25-fold increase.
The number of survivors who reported no limitations also increased, but not by as much. That group grew 1.34-fold during the study period.
For context, “the 70% prevalence of functional limitation among survivors in 2018 is nearly twice that of the general population,” the authors wrote.
Patients surveyed on function
Functional limitation was defined as “self-reported difficulty performing any of 12 routine physical or social activities without assistance.” Examples of the activities included difficulty sitting for more than 2 hours, difficulty participating in social activities or difficulty pushing or pulling an object the size of a living room chair.
Over the 2 decades analyzed, the adjusted prevalence of functional limitation was highest among survivors of pancreatic cancer (80.3%) and lung cancer (76.5%). Prevalence was lowest for survivors of melanoma (62.2%), breast (61.8%) and prostate (59.5%) cancers.
Not just a result of living longer
Mr. Patel told this publication that one assumption people might make when they read these results is that people are just living longer with cancer and losing functional ability accordingly.
“But, in fact, we found that the youngest [– those less than 65 years–] actually contributed to this trend more than the oldest people, which means it’s not just [happening], because people are getting older,” he said.
Hispanic and Black individuals had disproportionately higher increases in functional limitation; percentage point increases over the 2 decades were 19.5 for Black people, 25.1 for Hispanic people and 12.5 for White people. There may be a couple of reasons for that, Mr. Patel noted.
Those who are Black or Hispanic tend to have less access to cancer survivorship care for reasons including insurance status and historic health care inequities, he noted.
“The other potential reason is that they have had less access to cancer care historically. And if, 20 years ago Black and Hispanic individuals didn’t have access to some chemotherapies, and now they do, maybe it’s the increased access to care that’s causing these functional limitations. Because chemotherapy can sometimes be very toxic. It may be sort of a catch-up toxicity,” he said.
Quality of life beyond survivorship
Mr. Patel said the results seem to call for building on improved survival rates by tracking and improving function.
“It’s good to celebrate that there are more survivors. But now that we can keep people alive longer, maybe we can shift gears to improving their quality of life,” he said.
The more-than-doubling of functional limitations over 2 decades “is a very sobering trend,” he noted, while pointing out that the functional limitations applied to 8 million people in the United States – people whose needs are not being met.
There’s no sign of the trend stopping, he continued. “We saw no downward trend, only an upward trend.”
Increasingly, including functionality as an endpoint in cancer trials, in addition to improvements in mortality, is one place to start, he added.
“Our findings suggest an urgent need for care teams to understand and address function, for researchers to evaluate function as a core outcome in trials, and for health systems and policy makers to reimagine survivorship care, recognizing the burden of cancer and its treatment on physical, psychosocial, and cognitive function,” the authors wrote in their paper. Limitations of the study include the potential for recall bias, lack of cancer staging or treatment information, and the subjective perception of function.
A coauthor reported personal fees from Astellas, AstraZeneca, AAA, Blue Earth, Janssen, Lantheus, Myovant, Myriad Genetics, Novartis, Telix, and Sanofi, as well as grants from Pfizer and Bayer during the conduct of the study. No other disclosures were reported.
Vishal Patel, BS, a student at the Dell Medical School at The University of Texas at Austin, and colleagues identified 51,258 cancer survivors from the National Health Interview Survey, representing a weighted population of approximately 178.8 million from 1999 to 2018.
Most survivors were women (60.2%) and were at least 65 years old (55.4%). In 1999, 3.6 million weighted survivors reported functional limitation. In 2018, the number increased to 8.2 million, a 2.25-fold increase.
The number of survivors who reported no limitations also increased, but not by as much. That group grew 1.34-fold during the study period.
For context, “the 70% prevalence of functional limitation among survivors in 2018 is nearly twice that of the general population,” the authors wrote.
Patients surveyed on function
Functional limitation was defined as “self-reported difficulty performing any of 12 routine physical or social activities without assistance.” Examples of the activities included difficulty sitting for more than 2 hours, difficulty participating in social activities or difficulty pushing or pulling an object the size of a living room chair.
Over the 2 decades analyzed, the adjusted prevalence of functional limitation was highest among survivors of pancreatic cancer (80.3%) and lung cancer (76.5%). Prevalence was lowest for survivors of melanoma (62.2%), breast (61.8%) and prostate (59.5%) cancers.
Not just a result of living longer
Mr. Patel told this publication that one assumption people might make when they read these results is that people are just living longer with cancer and losing functional ability accordingly.
“But, in fact, we found that the youngest [– those less than 65 years–] actually contributed to this trend more than the oldest people, which means it’s not just [happening], because people are getting older,” he said.
Hispanic and Black individuals had disproportionately higher increases in functional limitation; percentage point increases over the 2 decades were 19.5 for Black people, 25.1 for Hispanic people and 12.5 for White people. There may be a couple of reasons for that, Mr. Patel noted.
Those who are Black or Hispanic tend to have less access to cancer survivorship care for reasons including insurance status and historic health care inequities, he noted.
“The other potential reason is that they have had less access to cancer care historically. And if, 20 years ago Black and Hispanic individuals didn’t have access to some chemotherapies, and now they do, maybe it’s the increased access to care that’s causing these functional limitations. Because chemotherapy can sometimes be very toxic. It may be sort of a catch-up toxicity,” he said.
Quality of life beyond survivorship
Mr. Patel said the results seem to call for building on improved survival rates by tracking and improving function.
“It’s good to celebrate that there are more survivors. But now that we can keep people alive longer, maybe we can shift gears to improving their quality of life,” he said.
The more-than-doubling of functional limitations over 2 decades “is a very sobering trend,” he noted, while pointing out that the functional limitations applied to 8 million people in the United States – people whose needs are not being met.
There’s no sign of the trend stopping, he continued. “We saw no downward trend, only an upward trend.”
Increasingly, including functionality as an endpoint in cancer trials, in addition to improvements in mortality, is one place to start, he added.
“Our findings suggest an urgent need for care teams to understand and address function, for researchers to evaluate function as a core outcome in trials, and for health systems and policy makers to reimagine survivorship care, recognizing the burden of cancer and its treatment on physical, psychosocial, and cognitive function,” the authors wrote in their paper. Limitations of the study include the potential for recall bias, lack of cancer staging or treatment information, and the subjective perception of function.
A coauthor reported personal fees from Astellas, AstraZeneca, AAA, Blue Earth, Janssen, Lantheus, Myovant, Myriad Genetics, Novartis, Telix, and Sanofi, as well as grants from Pfizer and Bayer during the conduct of the study. No other disclosures were reported.
Vishal Patel, BS, a student at the Dell Medical School at The University of Texas at Austin, and colleagues identified 51,258 cancer survivors from the National Health Interview Survey, representing a weighted population of approximately 178.8 million from 1999 to 2018.
Most survivors were women (60.2%) and were at least 65 years old (55.4%). In 1999, 3.6 million weighted survivors reported functional limitation. In 2018, the number increased to 8.2 million, a 2.25-fold increase.
The number of survivors who reported no limitations also increased, but not by as much. That group grew 1.34-fold during the study period.
For context, “the 70% prevalence of functional limitation among survivors in 2018 is nearly twice that of the general population,” the authors wrote.
Patients surveyed on function
Functional limitation was defined as “self-reported difficulty performing any of 12 routine physical or social activities without assistance.” Examples of the activities included difficulty sitting for more than 2 hours, difficulty participating in social activities or difficulty pushing or pulling an object the size of a living room chair.
Over the 2 decades analyzed, the adjusted prevalence of functional limitation was highest among survivors of pancreatic cancer (80.3%) and lung cancer (76.5%). Prevalence was lowest for survivors of melanoma (62.2%), breast (61.8%) and prostate (59.5%) cancers.
Not just a result of living longer
Mr. Patel told this publication that one assumption people might make when they read these results is that people are just living longer with cancer and losing functional ability accordingly.
“But, in fact, we found that the youngest [– those less than 65 years–] actually contributed to this trend more than the oldest people, which means it’s not just [happening], because people are getting older,” he said.
Hispanic and Black individuals had disproportionately higher increases in functional limitation; percentage point increases over the 2 decades were 19.5 for Black people, 25.1 for Hispanic people and 12.5 for White people. There may be a couple of reasons for that, Mr. Patel noted.
Those who are Black or Hispanic tend to have less access to cancer survivorship care for reasons including insurance status and historic health care inequities, he noted.
“The other potential reason is that they have had less access to cancer care historically. And if, 20 years ago Black and Hispanic individuals didn’t have access to some chemotherapies, and now they do, maybe it’s the increased access to care that’s causing these functional limitations. Because chemotherapy can sometimes be very toxic. It may be sort of a catch-up toxicity,” he said.
Quality of life beyond survivorship
Mr. Patel said the results seem to call for building on improved survival rates by tracking and improving function.
“It’s good to celebrate that there are more survivors. But now that we can keep people alive longer, maybe we can shift gears to improving their quality of life,” he said.
The more-than-doubling of functional limitations over 2 decades “is a very sobering trend,” he noted, while pointing out that the functional limitations applied to 8 million people in the United States – people whose needs are not being met.
There’s no sign of the trend stopping, he continued. “We saw no downward trend, only an upward trend.”
Increasingly, including functionality as an endpoint in cancer trials, in addition to improvements in mortality, is one place to start, he added.
“Our findings suggest an urgent need for care teams to understand and address function, for researchers to evaluate function as a core outcome in trials, and for health systems and policy makers to reimagine survivorship care, recognizing the burden of cancer and its treatment on physical, psychosocial, and cognitive function,” the authors wrote in their paper. Limitations of the study include the potential for recall bias, lack of cancer staging or treatment information, and the subjective perception of function.
A coauthor reported personal fees from Astellas, AstraZeneca, AAA, Blue Earth, Janssen, Lantheus, Myovant, Myriad Genetics, Novartis, Telix, and Sanofi, as well as grants from Pfizer and Bayer during the conduct of the study. No other disclosures were reported.
FROM JAMA ONCOLOGY
The breathtaking effects of climate change
To see the harmful effects of climate change firsthand, you need look no farther than the nearest pulmonary clinic.
The causes and effects are unmistakable: pollen storms leading to allergy sufferers flooding into allergists’ offices; rising air pollution levels increasing risk for obstructive airway diseases, cardiopulmonary complications, and non–small cell lung cancer; melting snowpacks and atmospheric rivers inundating neighborhoods and leaving moldy debris and incipient fungal infections in their wake.
“The reason why we think climate change is going to change the type of disease patterns and the severity of illness that we see in patients with respiratory diseases is that it changes a lot of the environment as well as the exposures,” said Bathmapriya Balakrishnan, BMedSci, BMBS, from the section of Pulmonary, Critical Care, and Sleep Medicine in the department of medicine at West Virginia University, Morgantown.
“What we’re going to see is not just new diseases but also exacerbation of chronic diseases, things like asthma [and] COPD. And there’s also concern that patients who are otherwise healthy, because they now have more exposures that are due to climate change, can then develop these diseases,” she said in an interview.
Ms. Balakrishnan is the lead author of a comprehensive, evidence-based review focused on the effects of climate change and air pollution across the spectrum of pulmonary disorders. The review is published online ahead of print in the journal Chest.
“ To inform health care providers of evidence-based methods and improve patient counselling, further research regarding measures that limit exposure is needed. Empowering patients with resources to monitor air quality and minimize exposure is a key preventative measure for decreasing morbidity and mortality while improving quality of life,” Ms. Balakrishnan and colleagues write.
Similarly, in a statement on the effects of climate change on respiratory health, the American Public Health Association succinctly summarized the problem: “Warmer temperatures lead to an increase in pollutants and allergens. Poor air quality leads to reduced lung function, increased risk of asthma complications, heart attacks, heart failure, and death. Air pollution and allergens are the main exposures affecting lung and heart health in this changing climate.”
Early spring
Stanley Fineman, MD, MBA, a past president of the American College of Allergy, Asthma, & Immunology and an allergist in private practice in Atlanta, has seen firsthand how global warming and an earlier start to spring allergy season is affecting his patients.
“The season, at least in our area metro Atlanta, started earlier and has been lasting longer. The pollen counts are very high,” he told this news organization.
“In February we started seeing pollen counts over 1,000 [grams per cubic meter], which is unheard of, and in March about half the days we counted levels that were over 1,000, which is also unheard of. In April it was over 1,000 almost half the days.”
Dr. Fineman and colleagues both in Atlanta and across the country have reported sharp increases in the proportion of new adult patients and in existing patients who have experienced exacerbation of previously mild disease.
“Probably what’s happened is that they may have had some allergic sensitivity that resulted in milder manifestations, but this year they’re getting major manifestations,” Dr. Fineman said.
In a 2014 article in the journal European Respiratory Review, Gennaro D’Amato, MD, from High Speciality Hospital Antonio Cardarelli, Naples, Italy, and colleagues outlined the main effects of climate on pollen levels: “1) an increase in plant growth and faster plant growth; 2) an increase in the amount of pollen produced by each plant; 3) an increase in the amount of allergenic proteins contained in pollen; 4) an increase in the start time of plant growth and, therefore, the start of pollen production; 5) an earlier and longer pollen season; 6) change in the geospatial distribution of pollen, that is plant ranges and long-distance atmospheric transport moving polewards,” they write.
Bad air
In addition to pollen, the ambient air in many places is increasingly becoming saturated with bioallergenic proteins such as bacteria, viruses, animal dander, insects, molds, and plant species, Ms. Balakrishnan and colleagues noted, adding that “atmospheric levels of carbon dioxide have also been found to increase pollen productivity. These changes result in greater over-the-counter medication use, emergency department visits, and outpatient visits for respiratory illnesses.”
The rash of violent storms that has washed over much of the United States in recent months is also likely to increase the incidence of so-called “thunderstorm asthma,” caused when large quantities of respirable particulate matter are released before or during a thunderstorm.
Air pollution from the burning of carbon-based fuels and from wildfires sparked by hotter and drier conditions increase airborne particulate matter that can seriously exacerbate asthma, COPD, and other obstructive airway conditions.
In addition, as previously reported by Medscape, exposure to particulate matter has been implicated as a possible cause of non–small cell lung cancer in persons who have never smoked.
Critical care challenges
Among the myriad other effects of climate change postulated in evidence enumerated by Ms. Balakrishnan and colleagues are chest infections and pleural diseases, such as aspergillosis infections that occur after catastrophic flooding; increased incidence of Mycobacterium avium complex infections and hypersensitivity pneumonitis; increased demands on critical care specialists from natural disasters; pollution-induced cardiac arrest; and heat prostration and heat stroke from increasingly prevalent heat waves.
The reviewers also examined evidence suggesting links between climate change and pulmonary hypertension, interstitial lung disease, sleep disorders, and occupational pulmonary disorders.
Power to the patients
“Pulmonologists should counsel patients on ways to minimize outdoor and indoor pollution, using tight-fitting respirators and home air-purifying systems without encroaching on patients’ beliefs and choices,” the authors advise.
“Empowering patients with resources to monitor air quality daily, in inclement weather, and during disasters would help minimize exposure and thus improve overall health. The pulmonologist can play an important role in emphasizing the impact of climate change on pulmonary disorders during patient care encounters,” they write.
Ms. Balakrishan adds that another important mitigation measure that can be taken today is education.
“In medical school we don’t really learn about the impact of climate change – at least in my generation of physicians, climate change or global warming weren’t part of the medical curriculum – but now I think that there’s a lot of advocacy work being done by medical students who actually want more education on climate change and its effects on pulmonary diseases,” she said.
The study by Ms. Balakrishnan and colleagues was unfunded. Ms. Balakrishnan reports no relevant financial relationships. Co-author Mary-Beth Scholand, MD, has received personal fees from serving on advisory boards and speakers bureaus for Genentech, Boehringer Ingelheim, Veracyte, and United Therapeutics. Co-author Sean Callahan, MD, has received personal fees for serving on advisory boards for Gilead and Boehringer Ingelheim. Dr. Fineman reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
To see the harmful effects of climate change firsthand, you need look no farther than the nearest pulmonary clinic.
The causes and effects are unmistakable: pollen storms leading to allergy sufferers flooding into allergists’ offices; rising air pollution levels increasing risk for obstructive airway diseases, cardiopulmonary complications, and non–small cell lung cancer; melting snowpacks and atmospheric rivers inundating neighborhoods and leaving moldy debris and incipient fungal infections in their wake.
“The reason why we think climate change is going to change the type of disease patterns and the severity of illness that we see in patients with respiratory diseases is that it changes a lot of the environment as well as the exposures,” said Bathmapriya Balakrishnan, BMedSci, BMBS, from the section of Pulmonary, Critical Care, and Sleep Medicine in the department of medicine at West Virginia University, Morgantown.
“What we’re going to see is not just new diseases but also exacerbation of chronic diseases, things like asthma [and] COPD. And there’s also concern that patients who are otherwise healthy, because they now have more exposures that are due to climate change, can then develop these diseases,” she said in an interview.
Ms. Balakrishnan is the lead author of a comprehensive, evidence-based review focused on the effects of climate change and air pollution across the spectrum of pulmonary disorders. The review is published online ahead of print in the journal Chest.
“ To inform health care providers of evidence-based methods and improve patient counselling, further research regarding measures that limit exposure is needed. Empowering patients with resources to monitor air quality and minimize exposure is a key preventative measure for decreasing morbidity and mortality while improving quality of life,” Ms. Balakrishnan and colleagues write.
Similarly, in a statement on the effects of climate change on respiratory health, the American Public Health Association succinctly summarized the problem: “Warmer temperatures lead to an increase in pollutants and allergens. Poor air quality leads to reduced lung function, increased risk of asthma complications, heart attacks, heart failure, and death. Air pollution and allergens are the main exposures affecting lung and heart health in this changing climate.”
Early spring
Stanley Fineman, MD, MBA, a past president of the American College of Allergy, Asthma, & Immunology and an allergist in private practice in Atlanta, has seen firsthand how global warming and an earlier start to spring allergy season is affecting his patients.
“The season, at least in our area metro Atlanta, started earlier and has been lasting longer. The pollen counts are very high,” he told this news organization.
“In February we started seeing pollen counts over 1,000 [grams per cubic meter], which is unheard of, and in March about half the days we counted levels that were over 1,000, which is also unheard of. In April it was over 1,000 almost half the days.”
Dr. Fineman and colleagues both in Atlanta and across the country have reported sharp increases in the proportion of new adult patients and in existing patients who have experienced exacerbation of previously mild disease.
“Probably what’s happened is that they may have had some allergic sensitivity that resulted in milder manifestations, but this year they’re getting major manifestations,” Dr. Fineman said.
In a 2014 article in the journal European Respiratory Review, Gennaro D’Amato, MD, from High Speciality Hospital Antonio Cardarelli, Naples, Italy, and colleagues outlined the main effects of climate on pollen levels: “1) an increase in plant growth and faster plant growth; 2) an increase in the amount of pollen produced by each plant; 3) an increase in the amount of allergenic proteins contained in pollen; 4) an increase in the start time of plant growth and, therefore, the start of pollen production; 5) an earlier and longer pollen season; 6) change in the geospatial distribution of pollen, that is plant ranges and long-distance atmospheric transport moving polewards,” they write.
Bad air
In addition to pollen, the ambient air in many places is increasingly becoming saturated with bioallergenic proteins such as bacteria, viruses, animal dander, insects, molds, and plant species, Ms. Balakrishnan and colleagues noted, adding that “atmospheric levels of carbon dioxide have also been found to increase pollen productivity. These changes result in greater over-the-counter medication use, emergency department visits, and outpatient visits for respiratory illnesses.”
The rash of violent storms that has washed over much of the United States in recent months is also likely to increase the incidence of so-called “thunderstorm asthma,” caused when large quantities of respirable particulate matter are released before or during a thunderstorm.
Air pollution from the burning of carbon-based fuels and from wildfires sparked by hotter and drier conditions increase airborne particulate matter that can seriously exacerbate asthma, COPD, and other obstructive airway conditions.
In addition, as previously reported by Medscape, exposure to particulate matter has been implicated as a possible cause of non–small cell lung cancer in persons who have never smoked.
Critical care challenges
Among the myriad other effects of climate change postulated in evidence enumerated by Ms. Balakrishnan and colleagues are chest infections and pleural diseases, such as aspergillosis infections that occur after catastrophic flooding; increased incidence of Mycobacterium avium complex infections and hypersensitivity pneumonitis; increased demands on critical care specialists from natural disasters; pollution-induced cardiac arrest; and heat prostration and heat stroke from increasingly prevalent heat waves.
The reviewers also examined evidence suggesting links between climate change and pulmonary hypertension, interstitial lung disease, sleep disorders, and occupational pulmonary disorders.
Power to the patients
“Pulmonologists should counsel patients on ways to minimize outdoor and indoor pollution, using tight-fitting respirators and home air-purifying systems without encroaching on patients’ beliefs and choices,” the authors advise.
“Empowering patients with resources to monitor air quality daily, in inclement weather, and during disasters would help minimize exposure and thus improve overall health. The pulmonologist can play an important role in emphasizing the impact of climate change on pulmonary disorders during patient care encounters,” they write.
Ms. Balakrishan adds that another important mitigation measure that can be taken today is education.
“In medical school we don’t really learn about the impact of climate change – at least in my generation of physicians, climate change or global warming weren’t part of the medical curriculum – but now I think that there’s a lot of advocacy work being done by medical students who actually want more education on climate change and its effects on pulmonary diseases,” she said.
The study by Ms. Balakrishnan and colleagues was unfunded. Ms. Balakrishnan reports no relevant financial relationships. Co-author Mary-Beth Scholand, MD, has received personal fees from serving on advisory boards and speakers bureaus for Genentech, Boehringer Ingelheim, Veracyte, and United Therapeutics. Co-author Sean Callahan, MD, has received personal fees for serving on advisory boards for Gilead and Boehringer Ingelheim. Dr. Fineman reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
To see the harmful effects of climate change firsthand, you need look no farther than the nearest pulmonary clinic.
The causes and effects are unmistakable: pollen storms leading to allergy sufferers flooding into allergists’ offices; rising air pollution levels increasing risk for obstructive airway diseases, cardiopulmonary complications, and non–small cell lung cancer; melting snowpacks and atmospheric rivers inundating neighborhoods and leaving moldy debris and incipient fungal infections in their wake.
“The reason why we think climate change is going to change the type of disease patterns and the severity of illness that we see in patients with respiratory diseases is that it changes a lot of the environment as well as the exposures,” said Bathmapriya Balakrishnan, BMedSci, BMBS, from the section of Pulmonary, Critical Care, and Sleep Medicine in the department of medicine at West Virginia University, Morgantown.
“What we’re going to see is not just new diseases but also exacerbation of chronic diseases, things like asthma [and] COPD. And there’s also concern that patients who are otherwise healthy, because they now have more exposures that are due to climate change, can then develop these diseases,” she said in an interview.
Ms. Balakrishnan is the lead author of a comprehensive, evidence-based review focused on the effects of climate change and air pollution across the spectrum of pulmonary disorders. The review is published online ahead of print in the journal Chest.
“ To inform health care providers of evidence-based methods and improve patient counselling, further research regarding measures that limit exposure is needed. Empowering patients with resources to monitor air quality and minimize exposure is a key preventative measure for decreasing morbidity and mortality while improving quality of life,” Ms. Balakrishnan and colleagues write.
Similarly, in a statement on the effects of climate change on respiratory health, the American Public Health Association succinctly summarized the problem: “Warmer temperatures lead to an increase in pollutants and allergens. Poor air quality leads to reduced lung function, increased risk of asthma complications, heart attacks, heart failure, and death. Air pollution and allergens are the main exposures affecting lung and heart health in this changing climate.”
Early spring
Stanley Fineman, MD, MBA, a past president of the American College of Allergy, Asthma, & Immunology and an allergist in private practice in Atlanta, has seen firsthand how global warming and an earlier start to spring allergy season is affecting his patients.
“The season, at least in our area metro Atlanta, started earlier and has been lasting longer. The pollen counts are very high,” he told this news organization.
“In February we started seeing pollen counts over 1,000 [grams per cubic meter], which is unheard of, and in March about half the days we counted levels that were over 1,000, which is also unheard of. In April it was over 1,000 almost half the days.”
Dr. Fineman and colleagues both in Atlanta and across the country have reported sharp increases in the proportion of new adult patients and in existing patients who have experienced exacerbation of previously mild disease.
“Probably what’s happened is that they may have had some allergic sensitivity that resulted in milder manifestations, but this year they’re getting major manifestations,” Dr. Fineman said.
In a 2014 article in the journal European Respiratory Review, Gennaro D’Amato, MD, from High Speciality Hospital Antonio Cardarelli, Naples, Italy, and colleagues outlined the main effects of climate on pollen levels: “1) an increase in plant growth and faster plant growth; 2) an increase in the amount of pollen produced by each plant; 3) an increase in the amount of allergenic proteins contained in pollen; 4) an increase in the start time of plant growth and, therefore, the start of pollen production; 5) an earlier and longer pollen season; 6) change in the geospatial distribution of pollen, that is plant ranges and long-distance atmospheric transport moving polewards,” they write.
Bad air
In addition to pollen, the ambient air in many places is increasingly becoming saturated with bioallergenic proteins such as bacteria, viruses, animal dander, insects, molds, and plant species, Ms. Balakrishnan and colleagues noted, adding that “atmospheric levels of carbon dioxide have also been found to increase pollen productivity. These changes result in greater over-the-counter medication use, emergency department visits, and outpatient visits for respiratory illnesses.”
The rash of violent storms that has washed over much of the United States in recent months is also likely to increase the incidence of so-called “thunderstorm asthma,” caused when large quantities of respirable particulate matter are released before or during a thunderstorm.
Air pollution from the burning of carbon-based fuels and from wildfires sparked by hotter and drier conditions increase airborne particulate matter that can seriously exacerbate asthma, COPD, and other obstructive airway conditions.
In addition, as previously reported by Medscape, exposure to particulate matter has been implicated as a possible cause of non–small cell lung cancer in persons who have never smoked.
Critical care challenges
Among the myriad other effects of climate change postulated in evidence enumerated by Ms. Balakrishnan and colleagues are chest infections and pleural diseases, such as aspergillosis infections that occur after catastrophic flooding; increased incidence of Mycobacterium avium complex infections and hypersensitivity pneumonitis; increased demands on critical care specialists from natural disasters; pollution-induced cardiac arrest; and heat prostration and heat stroke from increasingly prevalent heat waves.
The reviewers also examined evidence suggesting links between climate change and pulmonary hypertension, interstitial lung disease, sleep disorders, and occupational pulmonary disorders.
Power to the patients
“Pulmonologists should counsel patients on ways to minimize outdoor and indoor pollution, using tight-fitting respirators and home air-purifying systems without encroaching on patients’ beliefs and choices,” the authors advise.
“Empowering patients with resources to monitor air quality daily, in inclement weather, and during disasters would help minimize exposure and thus improve overall health. The pulmonologist can play an important role in emphasizing the impact of climate change on pulmonary disorders during patient care encounters,” they write.
Ms. Balakrishan adds that another important mitigation measure that can be taken today is education.
“In medical school we don’t really learn about the impact of climate change – at least in my generation of physicians, climate change or global warming weren’t part of the medical curriculum – but now I think that there’s a lot of advocacy work being done by medical students who actually want more education on climate change and its effects on pulmonary diseases,” she said.
The study by Ms. Balakrishnan and colleagues was unfunded. Ms. Balakrishnan reports no relevant financial relationships. Co-author Mary-Beth Scholand, MD, has received personal fees from serving on advisory boards and speakers bureaus for Genentech, Boehringer Ingelheim, Veracyte, and United Therapeutics. Co-author Sean Callahan, MD, has received personal fees for serving on advisory boards for Gilead and Boehringer Ingelheim. Dr. Fineman reports no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Asthma tied to increased risk for multiple cancers
People with asthma have an elevated risk for a variety of cancers other than lung cancer, including melanoma as well as blood, kidney, and ovarian cancers, new research suggests.
But, the authors found, treatment with an inhaled steroid may lower that risk, perhaps by keeping inflammation in check.
“Using real-world data, our study is the first to provide evidence of a positive association between asthma and cancer risk in United States patients,” Yi Guo, PhD, with the University of Florida, Gainesville, said in a news release.
The study was published online in Cancer Medicine.
The relationship between chronic inflammation and cancer remains a key area of exploration in cancer etiology. Data show that the risk for developing cancer is higher in patients with chronic inflammatory diseases, and patients with asthma have complex and chronic inflammation. However, prior studies exploring a possible link between asthma and cancer have yielded mixed results.
To investigate further, Dr. Guo and colleagues analyzed electronic health records and claims data in the OneFlorida+ clinical research network for roughly 90,000 adults with asthma and a matched cohort of about 270,000 adults without asthma.
Multivariable analysis revealed that adults with asthma were more likely to develop cancer, compared with peers without asthma (hazard ratio, 1.36), the investigators found.
Adults with asthma had an elevated cancer risk for five of the 13 cancers assessed, including melanoma (HR, 1.98), ovarian cancer (HR, 1.88), lung cancer (HR, 1.56), kidney cancer (HR, 1.48), and blood cancer (HR, 1.26).
Compared with adults without asthma, those with asthma who did not treat it with an inhaled steroid had a more pronounced overall cancer risk, compared with those who were on an inhaled steroid (HR, 1.60 vs. 1.11).
For specific cancer types, the risk was elevated for nine of 13 cancers in patients with asthma not taking an inhaled steroid: prostate (HR, 1.50), lung (HR, 1.74), colorectal (HR, 1.51), blood (HR, 1.44), melanoma (HR, 2.05), corpus uteri (HR, 1.76), kidney (HR, 1.52), ovarian (HR, 2.31), and cervical (HR, 1.46).
In contrast, in patients with asthma who did use an inhaled steroid, an elevated cancer risk was observed for only two cancers, lung cancer (HR, 1.39) and melanoma (HR, 1.92), suggesting a potential protective effect of inhaled steroid use on cancer, the researchers said.
Although prior studies have shown a protective effect of inhaled steroid use on some cancers, potentially by reducing inflammation, the “speculative nature of chronic inflammation (asthma as a common example) as a driver for pan-cancer development requires more investigation,” Dr. Guo and colleagues cautioned.
And because of the observational nature of the current study, Dr. Guo’s team stressed that these findings do not prove a causal relationship between asthma and cancer.
“More in-depth studies using real-word data are needed to further explore the causal mechanisms of asthma on cancer risk,” the researchers concluded.
Funding for the study was provided in part by grants to the researchers from the National Institutes of Health, National Cancer Institute, National Institute on Aging, and the Centers for Disease Control and Prevention. This project was supported by the Cancer Informatics Shared Resource in the University of Florida Health Cancer Center. The authors have disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
People with asthma have an elevated risk for a variety of cancers other than lung cancer, including melanoma as well as blood, kidney, and ovarian cancers, new research suggests.
But, the authors found, treatment with an inhaled steroid may lower that risk, perhaps by keeping inflammation in check.
“Using real-world data, our study is the first to provide evidence of a positive association between asthma and cancer risk in United States patients,” Yi Guo, PhD, with the University of Florida, Gainesville, said in a news release.
The study was published online in Cancer Medicine.
The relationship between chronic inflammation and cancer remains a key area of exploration in cancer etiology. Data show that the risk for developing cancer is higher in patients with chronic inflammatory diseases, and patients with asthma have complex and chronic inflammation. However, prior studies exploring a possible link between asthma and cancer have yielded mixed results.
To investigate further, Dr. Guo and colleagues analyzed electronic health records and claims data in the OneFlorida+ clinical research network for roughly 90,000 adults with asthma and a matched cohort of about 270,000 adults without asthma.
Multivariable analysis revealed that adults with asthma were more likely to develop cancer, compared with peers without asthma (hazard ratio, 1.36), the investigators found.
Adults with asthma had an elevated cancer risk for five of the 13 cancers assessed, including melanoma (HR, 1.98), ovarian cancer (HR, 1.88), lung cancer (HR, 1.56), kidney cancer (HR, 1.48), and blood cancer (HR, 1.26).
Compared with adults without asthma, those with asthma who did not treat it with an inhaled steroid had a more pronounced overall cancer risk, compared with those who were on an inhaled steroid (HR, 1.60 vs. 1.11).
For specific cancer types, the risk was elevated for nine of 13 cancers in patients with asthma not taking an inhaled steroid: prostate (HR, 1.50), lung (HR, 1.74), colorectal (HR, 1.51), blood (HR, 1.44), melanoma (HR, 2.05), corpus uteri (HR, 1.76), kidney (HR, 1.52), ovarian (HR, 2.31), and cervical (HR, 1.46).
In contrast, in patients with asthma who did use an inhaled steroid, an elevated cancer risk was observed for only two cancers, lung cancer (HR, 1.39) and melanoma (HR, 1.92), suggesting a potential protective effect of inhaled steroid use on cancer, the researchers said.
Although prior studies have shown a protective effect of inhaled steroid use on some cancers, potentially by reducing inflammation, the “speculative nature of chronic inflammation (asthma as a common example) as a driver for pan-cancer development requires more investigation,” Dr. Guo and colleagues cautioned.
And because of the observational nature of the current study, Dr. Guo’s team stressed that these findings do not prove a causal relationship between asthma and cancer.
“More in-depth studies using real-word data are needed to further explore the causal mechanisms of asthma on cancer risk,” the researchers concluded.
Funding for the study was provided in part by grants to the researchers from the National Institutes of Health, National Cancer Institute, National Institute on Aging, and the Centers for Disease Control and Prevention. This project was supported by the Cancer Informatics Shared Resource in the University of Florida Health Cancer Center. The authors have disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
People with asthma have an elevated risk for a variety of cancers other than lung cancer, including melanoma as well as blood, kidney, and ovarian cancers, new research suggests.
But, the authors found, treatment with an inhaled steroid may lower that risk, perhaps by keeping inflammation in check.
“Using real-world data, our study is the first to provide evidence of a positive association between asthma and cancer risk in United States patients,” Yi Guo, PhD, with the University of Florida, Gainesville, said in a news release.
The study was published online in Cancer Medicine.
The relationship between chronic inflammation and cancer remains a key area of exploration in cancer etiology. Data show that the risk for developing cancer is higher in patients with chronic inflammatory diseases, and patients with asthma have complex and chronic inflammation. However, prior studies exploring a possible link between asthma and cancer have yielded mixed results.
To investigate further, Dr. Guo and colleagues analyzed electronic health records and claims data in the OneFlorida+ clinical research network for roughly 90,000 adults with asthma and a matched cohort of about 270,000 adults without asthma.
Multivariable analysis revealed that adults with asthma were more likely to develop cancer, compared with peers without asthma (hazard ratio, 1.36), the investigators found.
Adults with asthma had an elevated cancer risk for five of the 13 cancers assessed, including melanoma (HR, 1.98), ovarian cancer (HR, 1.88), lung cancer (HR, 1.56), kidney cancer (HR, 1.48), and blood cancer (HR, 1.26).
Compared with adults without asthma, those with asthma who did not treat it with an inhaled steroid had a more pronounced overall cancer risk, compared with those who were on an inhaled steroid (HR, 1.60 vs. 1.11).
For specific cancer types, the risk was elevated for nine of 13 cancers in patients with asthma not taking an inhaled steroid: prostate (HR, 1.50), lung (HR, 1.74), colorectal (HR, 1.51), blood (HR, 1.44), melanoma (HR, 2.05), corpus uteri (HR, 1.76), kidney (HR, 1.52), ovarian (HR, 2.31), and cervical (HR, 1.46).
In contrast, in patients with asthma who did use an inhaled steroid, an elevated cancer risk was observed for only two cancers, lung cancer (HR, 1.39) and melanoma (HR, 1.92), suggesting a potential protective effect of inhaled steroid use on cancer, the researchers said.
Although prior studies have shown a protective effect of inhaled steroid use on some cancers, potentially by reducing inflammation, the “speculative nature of chronic inflammation (asthma as a common example) as a driver for pan-cancer development requires more investigation,” Dr. Guo and colleagues cautioned.
And because of the observational nature of the current study, Dr. Guo’s team stressed that these findings do not prove a causal relationship between asthma and cancer.
“More in-depth studies using real-word data are needed to further explore the causal mechanisms of asthma on cancer risk,” the researchers concluded.
Funding for the study was provided in part by grants to the researchers from the National Institutes of Health, National Cancer Institute, National Institute on Aging, and the Centers for Disease Control and Prevention. This project was supported by the Cancer Informatics Shared Resource in the University of Florida Health Cancer Center. The authors have disclosed no conflicts of interest.
A version of this article first appeared on Medscape.com.
Study shows higher obesity-related cancer mortality in areas with more fast food
based on data from a new cross-sectional study of more than 3,000 communities.
Although increased healthy eating has been associated with reduced risk of obesity and with reduced cancer incidence and mortality, access to healthier eating remains a challenge in communities with less access to grocery stores and healthy food options (food deserts) and/or easy access to convenience stores and fast food (food swamps), Malcolm Seth Bevel, PhD, of the Medical College of Georgia, Augusta, and colleagues, wrote in their paper, published in JAMA Oncology.
In addition, data on the association between food deserts and swamps and obesity-related cancer mortality are limited, they said.
“We felt that the study was important given the fact that obesity is an epidemic in the United States, and multiple factors contribute to obesity, especially adverse food environments,” Dr. Bevel said in an interview. “Also, I lived in these areas my whole life, and saw how it affected underserved populations. There was a story that needed to be told, so we’re telling it,” he said in an interview.
In a study, the researchers analyzed food access and cancer mortality data from 3,038 counties across the United States. The food access data came from the U.S. Department of Agriculture Food Environment Atlas (FEA) for the years 2012, 2014, 2015, 2017, and 2020. Data on obesity-related cancer mortality came from the Centers for Disease Control and Prevention for the years from 2010 to 2020.
Food desert scores were calculated through data from the FEA, and food swamp scores were based on the ratio of fast-food restaurants and convenience stores to grocery stores and farmers markets in a modification of the Retail Food Environment Index score.
The researchers used an age-adjusted, multiple regression model to determine the association between food desert and food swamp scores and obesity-related cancer mortality rates. Higher food swamp and food desert scores (defined as 20.0 to 58.0 or higher) were used to classify counties as having fewer healthy food resources. The primary outcome was obesity-related cancer mortality, defined as high or low (71.8 or higher per 100,000 individuals and less than 71.8 per 100,000 individuals, respectively).
Overall, high rates of obesity-related cancer mortality were 77% more likely in the counties that met the criteria for high food swamp scores (adjusted odds ratio 1.77). In addition, researchers found a positive dose-response relationship among three levels of both food desert scores and food swamp scores and obesity-related cancer mortality.
A total of 758 counties had obesity-related cancer mortality rates in the highest quartile. Compared to counties with low rates of obesity-related cancer mortality, counties with high rates of obesity-related cancer mortality also had a higher percentage of non-Hispanic Black residents (3.26% vs. 1.77%), higher percentage of adults older than 65 years (15.71% vs. 15.40%), higher rates of adult obesity (33.0% vs. 32.10%), and higher rates of adult diabetes (12.50% vs. 10.70%).
Possible explanations for the results include the lack of interest in grocery stores in neighborhoods with a population with a lower socioeconomic status, which can create a food desert, the researchers wrote in their discussion. “Coupled with the increasing growth rate of fast-food restaurants in recent years and the intentional advertisement of unhealthy foods in urban neighborhoods with [people of lower income], the food desert may transform into a food swamp,” they said.
The findings were limited by several factors including the study design, which did not allow for showing a causal association of food deserts and food swamps with obesity-related cancer mortality, the researchers noted. Other limitations included the use of groups rather than individuals, the potential misclassification of food stores, and the use of county-level data on race, ethnicity, and income, they wrote.
The results indicate that “food swamps appear to be a growing epidemic across the U.S., likely because of systemic issues, and should draw concern and conversation from local and state officials,” the researchers concluded.
Community-level investments can benefit individual health
Dr. Bevel said he was not surprised by the findings, as he has seen firsthand the lack of healthy food options and growth of unhealthy food options, especially for certain populations in certain communities. “Typically, these are people who have lower socioeconomic status, primarily non-Hispanic Black or African American or Hispanic American,” he said “I have watched people have to choose between getting fruits/vegetables versus their medications or running to fast food places to feed their families. What is truly surprising is that we’re not talking about people’s lived environment enough for my taste,” he said.
“I hope that our data and results can inform local and state policymakers to truly invest in all communities, such as funding for community gardens, and realize that adverse food environments, including the barriers in navigating these environments, have significant consequences on real people,” said Dr. Bevel. “Also, I hope that the results can help clinicians realize that a patient’s lived environment can truly affect their obesity and/or obesity-related cancer status; being cognizant of that is the first step in holistic, comprehensive care,” he said.
“One role that oncologists might be able to play in improving patients’ access to healthier food is to create and/or implement healthy lifestyle programs with gardening components to combat the poorest food environments that their patients likely reside in,” said Dr. Bevel. Clinicians also could consider the innovative approach of “food prescriptions” to help reduce the effects of deprived, built environments, he noted.
Looking ahead, next steps for research include determining the severity of association between food swamps and obesity-related cancer by varying factors such as cancer type, and examining any potential racial disparities between people living in these environments and obesity-related cancer, Dr. Bevel added.
Data provide foundation for multilevel interventions
The current study findings “raise a clarion call to elevate the discussion on food availability and access to ensure an equitable emphasis on both the importance of lifestyle factors and the upstream structural, economic, and environmental contexts that shape these behaviors at the individual level,” Karriem S. Watson, DHSc, MS, MPH, of the National Institutes of Health, Bethesda, Md., and Angela Odoms-Young, PhD, of Cornell University, Ithaca, N.Y., wrote in an accompanying editorial.
The findings provide a foundation for studies of obesity-related cancer outcomes that take the community environment into consideration, they added.
The causes of both obesity and cancer are complex, and the study findings suggest that the links between unhealthy food environments and obesity-related cancer may go beyond dietary consumption alone and extend to social and psychological factors, the editorialists noted.
“Whether dealing with the lack of access to healthy foods or an overabundance of unhealthy food, there is a critical need to develop additional research that explores the associations between obesity-related cancer mortality and food inequities,” they concluded.
The study received no outside funding. The researchers and the editorialists had no financial conflicts to disclose.
based on data from a new cross-sectional study of more than 3,000 communities.
Although increased healthy eating has been associated with reduced risk of obesity and with reduced cancer incidence and mortality, access to healthier eating remains a challenge in communities with less access to grocery stores and healthy food options (food deserts) and/or easy access to convenience stores and fast food (food swamps), Malcolm Seth Bevel, PhD, of the Medical College of Georgia, Augusta, and colleagues, wrote in their paper, published in JAMA Oncology.
In addition, data on the association between food deserts and swamps and obesity-related cancer mortality are limited, they said.
“We felt that the study was important given the fact that obesity is an epidemic in the United States, and multiple factors contribute to obesity, especially adverse food environments,” Dr. Bevel said in an interview. “Also, I lived in these areas my whole life, and saw how it affected underserved populations. There was a story that needed to be told, so we’re telling it,” he said in an interview.
In a study, the researchers analyzed food access and cancer mortality data from 3,038 counties across the United States. The food access data came from the U.S. Department of Agriculture Food Environment Atlas (FEA) for the years 2012, 2014, 2015, 2017, and 2020. Data on obesity-related cancer mortality came from the Centers for Disease Control and Prevention for the years from 2010 to 2020.
Food desert scores were calculated through data from the FEA, and food swamp scores were based on the ratio of fast-food restaurants and convenience stores to grocery stores and farmers markets in a modification of the Retail Food Environment Index score.
The researchers used an age-adjusted, multiple regression model to determine the association between food desert and food swamp scores and obesity-related cancer mortality rates. Higher food swamp and food desert scores (defined as 20.0 to 58.0 or higher) were used to classify counties as having fewer healthy food resources. The primary outcome was obesity-related cancer mortality, defined as high or low (71.8 or higher per 100,000 individuals and less than 71.8 per 100,000 individuals, respectively).
Overall, high rates of obesity-related cancer mortality were 77% more likely in the counties that met the criteria for high food swamp scores (adjusted odds ratio 1.77). In addition, researchers found a positive dose-response relationship among three levels of both food desert scores and food swamp scores and obesity-related cancer mortality.
A total of 758 counties had obesity-related cancer mortality rates in the highest quartile. Compared to counties with low rates of obesity-related cancer mortality, counties with high rates of obesity-related cancer mortality also had a higher percentage of non-Hispanic Black residents (3.26% vs. 1.77%), higher percentage of adults older than 65 years (15.71% vs. 15.40%), higher rates of adult obesity (33.0% vs. 32.10%), and higher rates of adult diabetes (12.50% vs. 10.70%).
Possible explanations for the results include the lack of interest in grocery stores in neighborhoods with a population with a lower socioeconomic status, which can create a food desert, the researchers wrote in their discussion. “Coupled with the increasing growth rate of fast-food restaurants in recent years and the intentional advertisement of unhealthy foods in urban neighborhoods with [people of lower income], the food desert may transform into a food swamp,” they said.
The findings were limited by several factors including the study design, which did not allow for showing a causal association of food deserts and food swamps with obesity-related cancer mortality, the researchers noted. Other limitations included the use of groups rather than individuals, the potential misclassification of food stores, and the use of county-level data on race, ethnicity, and income, they wrote.
The results indicate that “food swamps appear to be a growing epidemic across the U.S., likely because of systemic issues, and should draw concern and conversation from local and state officials,” the researchers concluded.
Community-level investments can benefit individual health
Dr. Bevel said he was not surprised by the findings, as he has seen firsthand the lack of healthy food options and growth of unhealthy food options, especially for certain populations in certain communities. “Typically, these are people who have lower socioeconomic status, primarily non-Hispanic Black or African American or Hispanic American,” he said “I have watched people have to choose between getting fruits/vegetables versus their medications or running to fast food places to feed their families. What is truly surprising is that we’re not talking about people’s lived environment enough for my taste,” he said.
“I hope that our data and results can inform local and state policymakers to truly invest in all communities, such as funding for community gardens, and realize that adverse food environments, including the barriers in navigating these environments, have significant consequences on real people,” said Dr. Bevel. “Also, I hope that the results can help clinicians realize that a patient’s lived environment can truly affect their obesity and/or obesity-related cancer status; being cognizant of that is the first step in holistic, comprehensive care,” he said.
“One role that oncologists might be able to play in improving patients’ access to healthier food is to create and/or implement healthy lifestyle programs with gardening components to combat the poorest food environments that their patients likely reside in,” said Dr. Bevel. Clinicians also could consider the innovative approach of “food prescriptions” to help reduce the effects of deprived, built environments, he noted.
Looking ahead, next steps for research include determining the severity of association between food swamps and obesity-related cancer by varying factors such as cancer type, and examining any potential racial disparities between people living in these environments and obesity-related cancer, Dr. Bevel added.
Data provide foundation for multilevel interventions
The current study findings “raise a clarion call to elevate the discussion on food availability and access to ensure an equitable emphasis on both the importance of lifestyle factors and the upstream structural, economic, and environmental contexts that shape these behaviors at the individual level,” Karriem S. Watson, DHSc, MS, MPH, of the National Institutes of Health, Bethesda, Md., and Angela Odoms-Young, PhD, of Cornell University, Ithaca, N.Y., wrote in an accompanying editorial.
The findings provide a foundation for studies of obesity-related cancer outcomes that take the community environment into consideration, they added.
The causes of both obesity and cancer are complex, and the study findings suggest that the links between unhealthy food environments and obesity-related cancer may go beyond dietary consumption alone and extend to social and psychological factors, the editorialists noted.
“Whether dealing with the lack of access to healthy foods or an overabundance of unhealthy food, there is a critical need to develop additional research that explores the associations between obesity-related cancer mortality and food inequities,” they concluded.
The study received no outside funding. The researchers and the editorialists had no financial conflicts to disclose.
based on data from a new cross-sectional study of more than 3,000 communities.
Although increased healthy eating has been associated with reduced risk of obesity and with reduced cancer incidence and mortality, access to healthier eating remains a challenge in communities with less access to grocery stores and healthy food options (food deserts) and/or easy access to convenience stores and fast food (food swamps), Malcolm Seth Bevel, PhD, of the Medical College of Georgia, Augusta, and colleagues, wrote in their paper, published in JAMA Oncology.
In addition, data on the association between food deserts and swamps and obesity-related cancer mortality are limited, they said.
“We felt that the study was important given the fact that obesity is an epidemic in the United States, and multiple factors contribute to obesity, especially adverse food environments,” Dr. Bevel said in an interview. “Also, I lived in these areas my whole life, and saw how it affected underserved populations. There was a story that needed to be told, so we’re telling it,” he said in an interview.
In a study, the researchers analyzed food access and cancer mortality data from 3,038 counties across the United States. The food access data came from the U.S. Department of Agriculture Food Environment Atlas (FEA) for the years 2012, 2014, 2015, 2017, and 2020. Data on obesity-related cancer mortality came from the Centers for Disease Control and Prevention for the years from 2010 to 2020.
Food desert scores were calculated through data from the FEA, and food swamp scores were based on the ratio of fast-food restaurants and convenience stores to grocery stores and farmers markets in a modification of the Retail Food Environment Index score.
The researchers used an age-adjusted, multiple regression model to determine the association between food desert and food swamp scores and obesity-related cancer mortality rates. Higher food swamp and food desert scores (defined as 20.0 to 58.0 or higher) were used to classify counties as having fewer healthy food resources. The primary outcome was obesity-related cancer mortality, defined as high or low (71.8 or higher per 100,000 individuals and less than 71.8 per 100,000 individuals, respectively).
Overall, high rates of obesity-related cancer mortality were 77% more likely in the counties that met the criteria for high food swamp scores (adjusted odds ratio 1.77). In addition, researchers found a positive dose-response relationship among three levels of both food desert scores and food swamp scores and obesity-related cancer mortality.
A total of 758 counties had obesity-related cancer mortality rates in the highest quartile. Compared to counties with low rates of obesity-related cancer mortality, counties with high rates of obesity-related cancer mortality also had a higher percentage of non-Hispanic Black residents (3.26% vs. 1.77%), higher percentage of adults older than 65 years (15.71% vs. 15.40%), higher rates of adult obesity (33.0% vs. 32.10%), and higher rates of adult diabetes (12.50% vs. 10.70%).
Possible explanations for the results include the lack of interest in grocery stores in neighborhoods with a population with a lower socioeconomic status, which can create a food desert, the researchers wrote in their discussion. “Coupled with the increasing growth rate of fast-food restaurants in recent years and the intentional advertisement of unhealthy foods in urban neighborhoods with [people of lower income], the food desert may transform into a food swamp,” they said.
The findings were limited by several factors including the study design, which did not allow for showing a causal association of food deserts and food swamps with obesity-related cancer mortality, the researchers noted. Other limitations included the use of groups rather than individuals, the potential misclassification of food stores, and the use of county-level data on race, ethnicity, and income, they wrote.
The results indicate that “food swamps appear to be a growing epidemic across the U.S., likely because of systemic issues, and should draw concern and conversation from local and state officials,” the researchers concluded.
Community-level investments can benefit individual health
Dr. Bevel said he was not surprised by the findings, as he has seen firsthand the lack of healthy food options and growth of unhealthy food options, especially for certain populations in certain communities. “Typically, these are people who have lower socioeconomic status, primarily non-Hispanic Black or African American or Hispanic American,” he said “I have watched people have to choose between getting fruits/vegetables versus their medications or running to fast food places to feed their families. What is truly surprising is that we’re not talking about people’s lived environment enough for my taste,” he said.
“I hope that our data and results can inform local and state policymakers to truly invest in all communities, such as funding for community gardens, and realize that adverse food environments, including the barriers in navigating these environments, have significant consequences on real people,” said Dr. Bevel. “Also, I hope that the results can help clinicians realize that a patient’s lived environment can truly affect their obesity and/or obesity-related cancer status; being cognizant of that is the first step in holistic, comprehensive care,” he said.
“One role that oncologists might be able to play in improving patients’ access to healthier food is to create and/or implement healthy lifestyle programs with gardening components to combat the poorest food environments that their patients likely reside in,” said Dr. Bevel. Clinicians also could consider the innovative approach of “food prescriptions” to help reduce the effects of deprived, built environments, he noted.
Looking ahead, next steps for research include determining the severity of association between food swamps and obesity-related cancer by varying factors such as cancer type, and examining any potential racial disparities between people living in these environments and obesity-related cancer, Dr. Bevel added.
Data provide foundation for multilevel interventions
The current study findings “raise a clarion call to elevate the discussion on food availability and access to ensure an equitable emphasis on both the importance of lifestyle factors and the upstream structural, economic, and environmental contexts that shape these behaviors at the individual level,” Karriem S. Watson, DHSc, MS, MPH, of the National Institutes of Health, Bethesda, Md., and Angela Odoms-Young, PhD, of Cornell University, Ithaca, N.Y., wrote in an accompanying editorial.
The findings provide a foundation for studies of obesity-related cancer outcomes that take the community environment into consideration, they added.
The causes of both obesity and cancer are complex, and the study findings suggest that the links between unhealthy food environments and obesity-related cancer may go beyond dietary consumption alone and extend to social and psychological factors, the editorialists noted.
“Whether dealing with the lack of access to healthy foods or an overabundance of unhealthy food, there is a critical need to develop additional research that explores the associations between obesity-related cancer mortality and food inequities,” they concluded.
The study received no outside funding. The researchers and the editorialists had no financial conflicts to disclose.
FROM JAMA ONCOLOGY
Expert discusses which diets are best, based on the evidence
according to a speaker at the annual meeting of the American College of Physicians.
“Evidence from studies can help clinicians and their patients develop a successful dietary management plan and achieve optimal health,” said internist Michelle Hauser, MD, clinical associate professor at Stanford (Calif.) University. She also discussed evidence-based techniques to support patients in maintaining dietary modifications.
Predominantly plant‐based diets
Popular predominantly plant‐based diets include a Mediterranean diet, healthy vegetarian diet, predominantly whole-food plant‐based (WFPB) diet, and a dietary approach to stop hypertension (DASH).
The DASH diet was originally designed to help patients manage their blood pressure, but evidence suggests that it also can help adults with obesity lose weight. In contrast to the DASH diet, the Mediterranean diet is not low-fat and not very restrictive. Yet the evidence suggests that the Mediterranean diet is not only helpful for losing weight but also can reduce the risk of various chronic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), and cancer, Dr. Hauser said. In addition, data suggest that the Mediterranean diet may reduce the risk of all-cause mortality and lower the levels of cholesterol.
“I like to highlight all these protective effects to my patients, because even if their goal is to lose weight, knowing that hard work pays off in additional ways can keep them motivated,” Dr. Hauser stated.
A healthy vegetarian diet and a WFPB diet are similar, and both are helpful in weight loss and management of total cholesterol and LDL‐C levels. Furthermore, healthy vegetarian and WFPB diets may reduce the risk of type 2 diabetes, CVD, and some cancers. Cohort study data suggest that progressively more vegetarian diets are associated with lower BMIs.
“My interpretation of these data is that predominantly plant-based diets rich in whole foods are healthful and can be done in a way that is sustainable for most,” said Dr. Hauser. However, this generally requires a lot of support at the outset to address gaps in knowledge, skills, and other potential barriers.
For example, she referred one obese patient at risk of diabetes and cardiovascular disease to a registered dietitian to develop a dietary plan. The patient also attended a behavioral medicine weight management program to learn strategies such as using smaller plates, and his family attended a healthy cooking class together to improve meal planning and cooking skills.
Time‐restricted feeding
There are numerous variations of time-restricted feeding, commonly referred to as intermittent fasting, but the principles are similar – limiting food intake to a specific window of time each day or week.
Although some studies have shown that time-restricted feeding may help patients reduce adiposity and improve lipid markers, most studies comparing time-restricted feeding to a calorie-restricted diet have shown little to no difference in weight-related outcomes, Dr. Hauser said.
These data suggest that time-restricted feeding may help patients with weight loss only if time restriction helps them reduce calorie intake. She also warned that time-restrictive feeding might cause late-night cravings and might not be helpful in individuals prone to food cravings.
Low‐carbohydrate and ketogenic diets
Losing muscle mass can prevent some people from dieting, but evidence suggests that a high-fat, very low-carbohydrate diet – also called a ketogenic diet – may help patients reduce weight and fat mass while preserving fat‐free mass, Dr. Hauser said.
The evidence regarding the usefulness of a low-carbohydrate (non-keto) diet is less clear because most studies compared it to a low-fat diet, and these two diets might lead to a similar extent of weight loss.
Rating the level of scientific evidence behind different diet options
Nutrition studies do no provide the same level of evidence as drug studies, said Dr. Hauser, because it is easier to conduct a randomized controlled trial of a drug versus placebo. Diets have many more variables, and it also takes much longer to observe most outcomes of a dietary change.
In addition, clinical trials of dietary interventions are typically short and focus on disease markers such as serum lipids and hemoglobin A1c levels. To obtain reliable information on the usefulness of a diet, researchers need to collect detailed health and lifestyle information from hundreds of thousands of people over several decades, which is not always feasible. “This is why meta-analyses of pooled dietary study data are more likely to yield dependable findings,” she noted.
Getting to know patients is essential to help them maintain diet modifications
When developing a diet plan for a patient, it is important to consider the sustainability of a dietary pattern. “The benefits of any healthy dietary change will only last as long as they can be maintained,” said Dr. Hauser. “Counseling someone on choosing an appropriate long-term dietary pattern requires getting to know them – taste preferences, food traditions, barriers, facilitators, food access, and time and cost restrictions.”
In an interview after the session, David Bittleman, MD, an internist at Veterans Affairs San Diego Health Care System, agreed that getting to know patients is essential for successfully advising them on diet.
“I always start developing a diet plan by trying to find out what [a patient’s] diet is like and what their goals are. I need to know what they are already doing in order to make suggestions about what they can do to make their diet healthier,” he said.
When asked about her approach to supporting patients in the long term, Dr. Hauser said that she recommends sequential, gradual changes. Dr. Hauser added that she suggests her patients prioritize implementing dietary changes that they are confident they can maintain.
Dr. Hauser and Dr. Bittleman report no relevant financial relationships.
according to a speaker at the annual meeting of the American College of Physicians.
“Evidence from studies can help clinicians and their patients develop a successful dietary management plan and achieve optimal health,” said internist Michelle Hauser, MD, clinical associate professor at Stanford (Calif.) University. She also discussed evidence-based techniques to support patients in maintaining dietary modifications.
Predominantly plant‐based diets
Popular predominantly plant‐based diets include a Mediterranean diet, healthy vegetarian diet, predominantly whole-food plant‐based (WFPB) diet, and a dietary approach to stop hypertension (DASH).
The DASH diet was originally designed to help patients manage their blood pressure, but evidence suggests that it also can help adults with obesity lose weight. In contrast to the DASH diet, the Mediterranean diet is not low-fat and not very restrictive. Yet the evidence suggests that the Mediterranean diet is not only helpful for losing weight but also can reduce the risk of various chronic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), and cancer, Dr. Hauser said. In addition, data suggest that the Mediterranean diet may reduce the risk of all-cause mortality and lower the levels of cholesterol.
“I like to highlight all these protective effects to my patients, because even if their goal is to lose weight, knowing that hard work pays off in additional ways can keep them motivated,” Dr. Hauser stated.
A healthy vegetarian diet and a WFPB diet are similar, and both are helpful in weight loss and management of total cholesterol and LDL‐C levels. Furthermore, healthy vegetarian and WFPB diets may reduce the risk of type 2 diabetes, CVD, and some cancers. Cohort study data suggest that progressively more vegetarian diets are associated with lower BMIs.
“My interpretation of these data is that predominantly plant-based diets rich in whole foods are healthful and can be done in a way that is sustainable for most,” said Dr. Hauser. However, this generally requires a lot of support at the outset to address gaps in knowledge, skills, and other potential barriers.
For example, she referred one obese patient at risk of diabetes and cardiovascular disease to a registered dietitian to develop a dietary plan. The patient also attended a behavioral medicine weight management program to learn strategies such as using smaller plates, and his family attended a healthy cooking class together to improve meal planning and cooking skills.
Time‐restricted feeding
There are numerous variations of time-restricted feeding, commonly referred to as intermittent fasting, but the principles are similar – limiting food intake to a specific window of time each day or week.
Although some studies have shown that time-restricted feeding may help patients reduce adiposity and improve lipid markers, most studies comparing time-restricted feeding to a calorie-restricted diet have shown little to no difference in weight-related outcomes, Dr. Hauser said.
These data suggest that time-restricted feeding may help patients with weight loss only if time restriction helps them reduce calorie intake. She also warned that time-restrictive feeding might cause late-night cravings and might not be helpful in individuals prone to food cravings.
Low‐carbohydrate and ketogenic diets
Losing muscle mass can prevent some people from dieting, but evidence suggests that a high-fat, very low-carbohydrate diet – also called a ketogenic diet – may help patients reduce weight and fat mass while preserving fat‐free mass, Dr. Hauser said.
The evidence regarding the usefulness of a low-carbohydrate (non-keto) diet is less clear because most studies compared it to a low-fat diet, and these two diets might lead to a similar extent of weight loss.
Rating the level of scientific evidence behind different diet options
Nutrition studies do no provide the same level of evidence as drug studies, said Dr. Hauser, because it is easier to conduct a randomized controlled trial of a drug versus placebo. Diets have many more variables, and it also takes much longer to observe most outcomes of a dietary change.
In addition, clinical trials of dietary interventions are typically short and focus on disease markers such as serum lipids and hemoglobin A1c levels. To obtain reliable information on the usefulness of a diet, researchers need to collect detailed health and lifestyle information from hundreds of thousands of people over several decades, which is not always feasible. “This is why meta-analyses of pooled dietary study data are more likely to yield dependable findings,” she noted.
Getting to know patients is essential to help them maintain diet modifications
When developing a diet plan for a patient, it is important to consider the sustainability of a dietary pattern. “The benefits of any healthy dietary change will only last as long as they can be maintained,” said Dr. Hauser. “Counseling someone on choosing an appropriate long-term dietary pattern requires getting to know them – taste preferences, food traditions, barriers, facilitators, food access, and time and cost restrictions.”
In an interview after the session, David Bittleman, MD, an internist at Veterans Affairs San Diego Health Care System, agreed that getting to know patients is essential for successfully advising them on diet.
“I always start developing a diet plan by trying to find out what [a patient’s] diet is like and what their goals are. I need to know what they are already doing in order to make suggestions about what they can do to make their diet healthier,” he said.
When asked about her approach to supporting patients in the long term, Dr. Hauser said that she recommends sequential, gradual changes. Dr. Hauser added that she suggests her patients prioritize implementing dietary changes that they are confident they can maintain.
Dr. Hauser and Dr. Bittleman report no relevant financial relationships.
according to a speaker at the annual meeting of the American College of Physicians.
“Evidence from studies can help clinicians and their patients develop a successful dietary management plan and achieve optimal health,” said internist Michelle Hauser, MD, clinical associate professor at Stanford (Calif.) University. She also discussed evidence-based techniques to support patients in maintaining dietary modifications.
Predominantly plant‐based diets
Popular predominantly plant‐based diets include a Mediterranean diet, healthy vegetarian diet, predominantly whole-food plant‐based (WFPB) diet, and a dietary approach to stop hypertension (DASH).
The DASH diet was originally designed to help patients manage their blood pressure, but evidence suggests that it also can help adults with obesity lose weight. In contrast to the DASH diet, the Mediterranean diet is not low-fat and not very restrictive. Yet the evidence suggests that the Mediterranean diet is not only helpful for losing weight but also can reduce the risk of various chronic diseases, including obesity, type 2 diabetes, cardiovascular disease (CVD), and cancer, Dr. Hauser said. In addition, data suggest that the Mediterranean diet may reduce the risk of all-cause mortality and lower the levels of cholesterol.
“I like to highlight all these protective effects to my patients, because even if their goal is to lose weight, knowing that hard work pays off in additional ways can keep them motivated,” Dr. Hauser stated.
A healthy vegetarian diet and a WFPB diet are similar, and both are helpful in weight loss and management of total cholesterol and LDL‐C levels. Furthermore, healthy vegetarian and WFPB diets may reduce the risk of type 2 diabetes, CVD, and some cancers. Cohort study data suggest that progressively more vegetarian diets are associated with lower BMIs.
“My interpretation of these data is that predominantly plant-based diets rich in whole foods are healthful and can be done in a way that is sustainable for most,” said Dr. Hauser. However, this generally requires a lot of support at the outset to address gaps in knowledge, skills, and other potential barriers.
For example, she referred one obese patient at risk of diabetes and cardiovascular disease to a registered dietitian to develop a dietary plan. The patient also attended a behavioral medicine weight management program to learn strategies such as using smaller plates, and his family attended a healthy cooking class together to improve meal planning and cooking skills.
Time‐restricted feeding
There are numerous variations of time-restricted feeding, commonly referred to as intermittent fasting, but the principles are similar – limiting food intake to a specific window of time each day or week.
Although some studies have shown that time-restricted feeding may help patients reduce adiposity and improve lipid markers, most studies comparing time-restricted feeding to a calorie-restricted diet have shown little to no difference in weight-related outcomes, Dr. Hauser said.
These data suggest that time-restricted feeding may help patients with weight loss only if time restriction helps them reduce calorie intake. She also warned that time-restrictive feeding might cause late-night cravings and might not be helpful in individuals prone to food cravings.
Low‐carbohydrate and ketogenic diets
Losing muscle mass can prevent some people from dieting, but evidence suggests that a high-fat, very low-carbohydrate diet – also called a ketogenic diet – may help patients reduce weight and fat mass while preserving fat‐free mass, Dr. Hauser said.
The evidence regarding the usefulness of a low-carbohydrate (non-keto) diet is less clear because most studies compared it to a low-fat diet, and these two diets might lead to a similar extent of weight loss.
Rating the level of scientific evidence behind different diet options
Nutrition studies do no provide the same level of evidence as drug studies, said Dr. Hauser, because it is easier to conduct a randomized controlled trial of a drug versus placebo. Diets have many more variables, and it also takes much longer to observe most outcomes of a dietary change.
In addition, clinical trials of dietary interventions are typically short and focus on disease markers such as serum lipids and hemoglobin A1c levels. To obtain reliable information on the usefulness of a diet, researchers need to collect detailed health and lifestyle information from hundreds of thousands of people over several decades, which is not always feasible. “This is why meta-analyses of pooled dietary study data are more likely to yield dependable findings,” she noted.
Getting to know patients is essential to help them maintain diet modifications
When developing a diet plan for a patient, it is important to consider the sustainability of a dietary pattern. “The benefits of any healthy dietary change will only last as long as they can be maintained,” said Dr. Hauser. “Counseling someone on choosing an appropriate long-term dietary pattern requires getting to know them – taste preferences, food traditions, barriers, facilitators, food access, and time and cost restrictions.”
In an interview after the session, David Bittleman, MD, an internist at Veterans Affairs San Diego Health Care System, agreed that getting to know patients is essential for successfully advising them on diet.
“I always start developing a diet plan by trying to find out what [a patient’s] diet is like and what their goals are. I need to know what they are already doing in order to make suggestions about what they can do to make their diet healthier,” he said.
When asked about her approach to supporting patients in the long term, Dr. Hauser said that she recommends sequential, gradual changes. Dr. Hauser added that she suggests her patients prioritize implementing dietary changes that they are confident they can maintain.
Dr. Hauser and Dr. Bittleman report no relevant financial relationships.
AT INTERNAL MEDICINE 2023
Plasma monitoring supports earlier osimertinib treatment in lung cancer patients
Previous studies have suggested that molecular progression of disease in patients with EGFR-mutant NSCLC, as measured by sequential plasma EGFR T790M, may precede radiological progression, as measured by Response Evaluation Criteria in Solid Tumors (RECIST).
However, the impact of these measures on timing of treatment changes and patient outcomes has not been examined, wrote Jordi Remon, MD, of Paris (France)–Saclay University and colleagues, in Annals of Oncology.
The European Organization for Research Treatment and Cancer Lung Cancer Group designed a phase 2 clinical trial known as APPLE to evaluate the use of sequential plasma EGFR T790M and determine the optimal sequencing for gefitinib and osimertinib in patients with EGFR-mutant NSCLC.
The researchers reported results from two randomized arms of the APPLE trial. In arm B, 52 patients received gefitinib until emergence of circulating tumor DNA (ctDNA) EGFR T790M mutation, based on the cobas EGFR test v2 (a real-time PCR test), or progression of disease based on Response Evaluation Criteria in Solid Tumors (RECIST). In arm C, 51 patients received gefitinib until disease progression based on RECIST. Both arms then switched to osimertinib. Patients randomized to a third arm (arm A) received osimertinib upfront until progression of disease based on RECIST, and they were not included in the current study.
The primary endpoint was progression-free survival (PFS) while receiving osimertinib at 18 months in patients who were originally randomized to gefitinib, then switched to osimertinib at the emergence of circulating tumor DNA. Secondary endpoints included PFS, overall response rate, overall survival, and brain PFS.
Patients entered the study between November 2017 and February 2020. A total of 75% and 65% of those in arms B and C, respectively, were female, approximately 65% had the mutation EGFR Del19, and approximately one-third had baseline brain metastases. In arm B, 17% of patients switched to osimertinib based on the emergence of ctDNA T790M mutation before progressive disease based on RECIST. The median time to molecular disease progression was 266 days.
More patients in arm B met the primary endpoint of PFS while receiving osimertinib at 18 months (67.2%) than in arm C (53.5%), after a median follow-up of 30 months.
As for secondary endpoints, the median PFS in the two arms was 22.0 months and 20.2 months, respectively. Median overall survival was 42.8 months in arm C and was not reached in arm B. The median brain PFS was 24.4 months for arm B and 21.4 months for arm C.
The benefits seen in the osimertinib patients may be due in part to the timing of the switch to correspond with molecular or radiological disease progression, the researchers wrote in their discussion.
In the future, more research is needed to determine whether molecular monitoring may impact patients’ outcomes, compared with monitoring based on radiological progression, they said.
The findings were limited by several factors, mainly the rapid evolution in the treatment landscape of EGFR-mutant NSCLC, the researchers noted.
Osimertinib is currently considered the preferred first-line treatment by most physicians, they said. “The APPLE trial is the first prospective study supporting the role of dynamic adaptive strategies based on ctDNA monitoring in patients with EGFR-mutant advanced NSCLC.”
The study was supported by AstraZeneca. Lead author Dr. Remon had no financial conflicts to disclose. Corresponding author Dr. Dziadziuszko disclosed honoraria for consultancy or lectures from AstraZeneca, Roche, Novartis, MSD, Takeda, Pfizer, Amgen, and Bristol-Myers Squibb.
Previous studies have suggested that molecular progression of disease in patients with EGFR-mutant NSCLC, as measured by sequential plasma EGFR T790M, may precede radiological progression, as measured by Response Evaluation Criteria in Solid Tumors (RECIST).
However, the impact of these measures on timing of treatment changes and patient outcomes has not been examined, wrote Jordi Remon, MD, of Paris (France)–Saclay University and colleagues, in Annals of Oncology.
The European Organization for Research Treatment and Cancer Lung Cancer Group designed a phase 2 clinical trial known as APPLE to evaluate the use of sequential plasma EGFR T790M and determine the optimal sequencing for gefitinib and osimertinib in patients with EGFR-mutant NSCLC.
The researchers reported results from two randomized arms of the APPLE trial. In arm B, 52 patients received gefitinib until emergence of circulating tumor DNA (ctDNA) EGFR T790M mutation, based on the cobas EGFR test v2 (a real-time PCR test), or progression of disease based on Response Evaluation Criteria in Solid Tumors (RECIST). In arm C, 51 patients received gefitinib until disease progression based on RECIST. Both arms then switched to osimertinib. Patients randomized to a third arm (arm A) received osimertinib upfront until progression of disease based on RECIST, and they were not included in the current study.
The primary endpoint was progression-free survival (PFS) while receiving osimertinib at 18 months in patients who were originally randomized to gefitinib, then switched to osimertinib at the emergence of circulating tumor DNA. Secondary endpoints included PFS, overall response rate, overall survival, and brain PFS.
Patients entered the study between November 2017 and February 2020. A total of 75% and 65% of those in arms B and C, respectively, were female, approximately 65% had the mutation EGFR Del19, and approximately one-third had baseline brain metastases. In arm B, 17% of patients switched to osimertinib based on the emergence of ctDNA T790M mutation before progressive disease based on RECIST. The median time to molecular disease progression was 266 days.
More patients in arm B met the primary endpoint of PFS while receiving osimertinib at 18 months (67.2%) than in arm C (53.5%), after a median follow-up of 30 months.
As for secondary endpoints, the median PFS in the two arms was 22.0 months and 20.2 months, respectively. Median overall survival was 42.8 months in arm C and was not reached in arm B. The median brain PFS was 24.4 months for arm B and 21.4 months for arm C.
The benefits seen in the osimertinib patients may be due in part to the timing of the switch to correspond with molecular or radiological disease progression, the researchers wrote in their discussion.
In the future, more research is needed to determine whether molecular monitoring may impact patients’ outcomes, compared with monitoring based on radiological progression, they said.
The findings were limited by several factors, mainly the rapid evolution in the treatment landscape of EGFR-mutant NSCLC, the researchers noted.
Osimertinib is currently considered the preferred first-line treatment by most physicians, they said. “The APPLE trial is the first prospective study supporting the role of dynamic adaptive strategies based on ctDNA monitoring in patients with EGFR-mutant advanced NSCLC.”
The study was supported by AstraZeneca. Lead author Dr. Remon had no financial conflicts to disclose. Corresponding author Dr. Dziadziuszko disclosed honoraria for consultancy or lectures from AstraZeneca, Roche, Novartis, MSD, Takeda, Pfizer, Amgen, and Bristol-Myers Squibb.
Previous studies have suggested that molecular progression of disease in patients with EGFR-mutant NSCLC, as measured by sequential plasma EGFR T790M, may precede radiological progression, as measured by Response Evaluation Criteria in Solid Tumors (RECIST).
However, the impact of these measures on timing of treatment changes and patient outcomes has not been examined, wrote Jordi Remon, MD, of Paris (France)–Saclay University and colleagues, in Annals of Oncology.
The European Organization for Research Treatment and Cancer Lung Cancer Group designed a phase 2 clinical trial known as APPLE to evaluate the use of sequential plasma EGFR T790M and determine the optimal sequencing for gefitinib and osimertinib in patients with EGFR-mutant NSCLC.
The researchers reported results from two randomized arms of the APPLE trial. In arm B, 52 patients received gefitinib until emergence of circulating tumor DNA (ctDNA) EGFR T790M mutation, based on the cobas EGFR test v2 (a real-time PCR test), or progression of disease based on Response Evaluation Criteria in Solid Tumors (RECIST). In arm C, 51 patients received gefitinib until disease progression based on RECIST. Both arms then switched to osimertinib. Patients randomized to a third arm (arm A) received osimertinib upfront until progression of disease based on RECIST, and they were not included in the current study.
The primary endpoint was progression-free survival (PFS) while receiving osimertinib at 18 months in patients who were originally randomized to gefitinib, then switched to osimertinib at the emergence of circulating tumor DNA. Secondary endpoints included PFS, overall response rate, overall survival, and brain PFS.
Patients entered the study between November 2017 and February 2020. A total of 75% and 65% of those in arms B and C, respectively, were female, approximately 65% had the mutation EGFR Del19, and approximately one-third had baseline brain metastases. In arm B, 17% of patients switched to osimertinib based on the emergence of ctDNA T790M mutation before progressive disease based on RECIST. The median time to molecular disease progression was 266 days.
More patients in arm B met the primary endpoint of PFS while receiving osimertinib at 18 months (67.2%) than in arm C (53.5%), after a median follow-up of 30 months.
As for secondary endpoints, the median PFS in the two arms was 22.0 months and 20.2 months, respectively. Median overall survival was 42.8 months in arm C and was not reached in arm B. The median brain PFS was 24.4 months for arm B and 21.4 months for arm C.
The benefits seen in the osimertinib patients may be due in part to the timing of the switch to correspond with molecular or radiological disease progression, the researchers wrote in their discussion.
In the future, more research is needed to determine whether molecular monitoring may impact patients’ outcomes, compared with monitoring based on radiological progression, they said.
The findings were limited by several factors, mainly the rapid evolution in the treatment landscape of EGFR-mutant NSCLC, the researchers noted.
Osimertinib is currently considered the preferred first-line treatment by most physicians, they said. “The APPLE trial is the first prospective study supporting the role of dynamic adaptive strategies based on ctDNA monitoring in patients with EGFR-mutant advanced NSCLC.”
The study was supported by AstraZeneca. Lead author Dr. Remon had no financial conflicts to disclose. Corresponding author Dr. Dziadziuszko disclosed honoraria for consultancy or lectures from AstraZeneca, Roche, Novartis, MSD, Takeda, Pfizer, Amgen, and Bristol-Myers Squibb.
FROM ANNALS OF ONCOLOGY