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M. Alexander Otto began his reporting career early in 1999 covering the pharmaceutical industry for a national pharmacists' magazine and freelancing for the Washington Post and other newspapers. He then joined BNA, now part of Bloomberg News, covering health law and the protection of people and animals in medical research. Alex next worked for the McClatchy Company. Based on his work, Alex won a year-long Knight Science Journalism Fellowship to MIT in 2008-2009. He joined the company shortly thereafter. Alex has a newspaper journalism degree from Syracuse (N.Y.) University and a master's degree in medical science -- a physician assistant degree -- from George Washington University. Alex is based in Seattle.
Better survival with extended letrozole in early-stage breast cancer
The approach “should be considered among the optimal standard endocrine treatments for postmenopausal patients with hormone receptor–positive breast cancer, regardless of the nodal status at diagnosis,” concluded investigators led by Lucia Del Mastro, MD, a medical oncologist at the University of Genoa, Italy.
Clinical practice guidelines recommend an individualized approach to decide the duration of treatment based on relapse risk and tolerability because no study until now has shown an overall survival benefit with extended aromatase inhibitor therapy. Based on “our results ... this statement is no longer supported by the evidence and should be updated,” they wrote.
The optimal duration or type of endocrine therapy has been uncertain; the team sought to bring more clarity to the issue.
Following 2-3 years of adjuvant tamoxifen, they randomized evenly 2,056 women at 69 hospitals in Italy to either 2-3 years or letrozole 2.5 mg once daily – the usual care control group – or 5 years. Women in the trial, dubbed GIM4, had stage I-III histologically proven and operable invasive cancer, with no signs of disease recurrence.
Twelve-year overall survival was 88% with extended letrozole, but 84% in the control arm (HR 0.77, 95% confidence interval, 0.60-0.98; P = 0.036).
Twelve-year disease-free survival was 67% in the extended group versus 62% in the control arm (HR 0.78, 95% CI, 0.65-0.93; P = 0.0064).
At a median follow-up of 11.7 years, disease-free survival (DFS) events occurred in 25.4% of control patients, but only 20.7% with extended aromatase inhibitor treatment.
It took 9.5 years for the survival curves to separate, suggesting “that the effect of letrozole takes several years to be seen,” the investigators said.
With the disease-free survival benefits shown in earlier trials and now better overall survival as well, it’s looking like “7-8 years of adjuvant therapy, including at least 5 years with an aromatase inhibitor, could be the optimal duration of adjuvant endocrine therapy in postmenopausal patients with breast cancer.” It probably represents “the best compromise between efficacy and side-effects,” they said.
Breast cancer oncologists Rachel L. Yung, MD, and Nancy E. Davidson, MD, both of the Fred Hutchinson Cancer Research Center, Seattle, agreed in an editorial.
For now, “the currently available data seem to recommend 5 years of aromatase inhibitor for postmenopausal women who have already completed 2-3 years of tamoxifen,” they said.
However, with 19.5% of control patients and 37.1% in the extended stopping treatment early, “GIM4 highlights that early therapy discontinuation remains a crucial issue ... better ways to promote adherence are sorely needed. Another area of focus is the identification of biomarkers that could [better] inform the optimal duration of therapy,” they said.
Longer duration of letrozole was associated with an increased incidence of arthralgia, myalgia, hypertension, and osteoporosis; however, there was no difference in the incidence of bone fractures.
There was also a slightly higher number of cardiovascular events (1% in the extended group, but fewer in the control arm) which is a known issue with aromatase inhibitors. There were three serious treatment-related adverse events in the control arm and eight in the extended group, but no deaths. The Italian investigators noted that because they enrolled only patients free of recurrence after 2-3 years of tamoxifen, the population with early relapse who were likely to be node-positive, was excluded, leaving only patients with a better prognosis. “On the other hand, patients with node-negative disease relapse later and are therefore captured by this trial with a long follow-up.”
The work was funded by Novartis and the Italian Ministry of Health. The investigators had numerous industry ties, including Dr. Del Mastro, who reported honoraria and nonfinancial support from Novartis, Roche, Pfizer, and others. The editorialists didn’t have any competing interests.
The approach “should be considered among the optimal standard endocrine treatments for postmenopausal patients with hormone receptor–positive breast cancer, regardless of the nodal status at diagnosis,” concluded investigators led by Lucia Del Mastro, MD, a medical oncologist at the University of Genoa, Italy.
Clinical practice guidelines recommend an individualized approach to decide the duration of treatment based on relapse risk and tolerability because no study until now has shown an overall survival benefit with extended aromatase inhibitor therapy. Based on “our results ... this statement is no longer supported by the evidence and should be updated,” they wrote.
The optimal duration or type of endocrine therapy has been uncertain; the team sought to bring more clarity to the issue.
Following 2-3 years of adjuvant tamoxifen, they randomized evenly 2,056 women at 69 hospitals in Italy to either 2-3 years or letrozole 2.5 mg once daily – the usual care control group – or 5 years. Women in the trial, dubbed GIM4, had stage I-III histologically proven and operable invasive cancer, with no signs of disease recurrence.
Twelve-year overall survival was 88% with extended letrozole, but 84% in the control arm (HR 0.77, 95% confidence interval, 0.60-0.98; P = 0.036).
Twelve-year disease-free survival was 67% in the extended group versus 62% in the control arm (HR 0.78, 95% CI, 0.65-0.93; P = 0.0064).
At a median follow-up of 11.7 years, disease-free survival (DFS) events occurred in 25.4% of control patients, but only 20.7% with extended aromatase inhibitor treatment.
It took 9.5 years for the survival curves to separate, suggesting “that the effect of letrozole takes several years to be seen,” the investigators said.
With the disease-free survival benefits shown in earlier trials and now better overall survival as well, it’s looking like “7-8 years of adjuvant therapy, including at least 5 years with an aromatase inhibitor, could be the optimal duration of adjuvant endocrine therapy in postmenopausal patients with breast cancer.” It probably represents “the best compromise between efficacy and side-effects,” they said.
Breast cancer oncologists Rachel L. Yung, MD, and Nancy E. Davidson, MD, both of the Fred Hutchinson Cancer Research Center, Seattle, agreed in an editorial.
For now, “the currently available data seem to recommend 5 years of aromatase inhibitor for postmenopausal women who have already completed 2-3 years of tamoxifen,” they said.
However, with 19.5% of control patients and 37.1% in the extended stopping treatment early, “GIM4 highlights that early therapy discontinuation remains a crucial issue ... better ways to promote adherence are sorely needed. Another area of focus is the identification of biomarkers that could [better] inform the optimal duration of therapy,” they said.
Longer duration of letrozole was associated with an increased incidence of arthralgia, myalgia, hypertension, and osteoporosis; however, there was no difference in the incidence of bone fractures.
There was also a slightly higher number of cardiovascular events (1% in the extended group, but fewer in the control arm) which is a known issue with aromatase inhibitors. There were three serious treatment-related adverse events in the control arm and eight in the extended group, but no deaths. The Italian investigators noted that because they enrolled only patients free of recurrence after 2-3 years of tamoxifen, the population with early relapse who were likely to be node-positive, was excluded, leaving only patients with a better prognosis. “On the other hand, patients with node-negative disease relapse later and are therefore captured by this trial with a long follow-up.”
The work was funded by Novartis and the Italian Ministry of Health. The investigators had numerous industry ties, including Dr. Del Mastro, who reported honoraria and nonfinancial support from Novartis, Roche, Pfizer, and others. The editorialists didn’t have any competing interests.
The approach “should be considered among the optimal standard endocrine treatments for postmenopausal patients with hormone receptor–positive breast cancer, regardless of the nodal status at diagnosis,” concluded investigators led by Lucia Del Mastro, MD, a medical oncologist at the University of Genoa, Italy.
Clinical practice guidelines recommend an individualized approach to decide the duration of treatment based on relapse risk and tolerability because no study until now has shown an overall survival benefit with extended aromatase inhibitor therapy. Based on “our results ... this statement is no longer supported by the evidence and should be updated,” they wrote.
The optimal duration or type of endocrine therapy has been uncertain; the team sought to bring more clarity to the issue.
Following 2-3 years of adjuvant tamoxifen, they randomized evenly 2,056 women at 69 hospitals in Italy to either 2-3 years or letrozole 2.5 mg once daily – the usual care control group – or 5 years. Women in the trial, dubbed GIM4, had stage I-III histologically proven and operable invasive cancer, with no signs of disease recurrence.
Twelve-year overall survival was 88% with extended letrozole, but 84% in the control arm (HR 0.77, 95% confidence interval, 0.60-0.98; P = 0.036).
Twelve-year disease-free survival was 67% in the extended group versus 62% in the control arm (HR 0.78, 95% CI, 0.65-0.93; P = 0.0064).
At a median follow-up of 11.7 years, disease-free survival (DFS) events occurred in 25.4% of control patients, but only 20.7% with extended aromatase inhibitor treatment.
It took 9.5 years for the survival curves to separate, suggesting “that the effect of letrozole takes several years to be seen,” the investigators said.
With the disease-free survival benefits shown in earlier trials and now better overall survival as well, it’s looking like “7-8 years of adjuvant therapy, including at least 5 years with an aromatase inhibitor, could be the optimal duration of adjuvant endocrine therapy in postmenopausal patients with breast cancer.” It probably represents “the best compromise between efficacy and side-effects,” they said.
Breast cancer oncologists Rachel L. Yung, MD, and Nancy E. Davidson, MD, both of the Fred Hutchinson Cancer Research Center, Seattle, agreed in an editorial.
For now, “the currently available data seem to recommend 5 years of aromatase inhibitor for postmenopausal women who have already completed 2-3 years of tamoxifen,” they said.
However, with 19.5% of control patients and 37.1% in the extended stopping treatment early, “GIM4 highlights that early therapy discontinuation remains a crucial issue ... better ways to promote adherence are sorely needed. Another area of focus is the identification of biomarkers that could [better] inform the optimal duration of therapy,” they said.
Longer duration of letrozole was associated with an increased incidence of arthralgia, myalgia, hypertension, and osteoporosis; however, there was no difference in the incidence of bone fractures.
There was also a slightly higher number of cardiovascular events (1% in the extended group, but fewer in the control arm) which is a known issue with aromatase inhibitors. There were three serious treatment-related adverse events in the control arm and eight in the extended group, but no deaths. The Italian investigators noted that because they enrolled only patients free of recurrence after 2-3 years of tamoxifen, the population with early relapse who were likely to be node-positive, was excluded, leaving only patients with a better prognosis. “On the other hand, patients with node-negative disease relapse later and are therefore captured by this trial with a long follow-up.”
The work was funded by Novartis and the Italian Ministry of Health. The investigators had numerous industry ties, including Dr. Del Mastro, who reported honoraria and nonfinancial support from Novartis, Roche, Pfizer, and others. The editorialists didn’t have any competing interests.
FROM THE LANCET ONCOLOGY
Twelve-month overall survival benefit with ribociclib for metastatic breast cancer
“Based on these results, ribociclib and letrozole should be considered the preferred treatment option,” said lead investigator Gabriel N. Hortobagyi, MD, a breast cancer medical oncologist at the University of Texas MD Anderson Cancer Center, Houston.
He presented the definitive overall survival results from MONALESSA-2 which randomized 668 patients equally and in the first line to either ribociclib or placebo on a background of standard dose letrozole.
At a median follow up of 6.6 years, median overall survival with ribociclib was 63.9 months versus 51.4 months in the placebo arm, a 24% reduction in the relative risk of death (P = .004).
It was the first report of a median overall survival (OS) exceeding 5 years in a phase 3 trial for advanced breast cancer. The estimated 6-year OS rate was 44.2% for ribociclib versus 32.0% with placebo.
“These are really impressive results” and support the use of CDK 4/6 inhibitors in the front-line setting,” said study discussant Gonzalo Gomez Abuin, MD, a medical oncologist at Hospital Alemán in Bueno Aires.
Ribociclib and other CDK 4/6 inhibitors have shown consistent progression-free survival benefit for metastatic disease, but ribociclib is the first of the major phase 3 trials with definitive overall survival results. They have “been long awaited,” Dr. Abuin said.
The overall survival benefit in MONALESSA-2 began to emerge at around 20 months and continued to increase over time.
Women had no prior CDK4/6 inhibitor treatment, chemotherapy, or endocrine therapy for metastatic disease. “They represented a pure first-line population,” Dr. Hortobagyi said.
Among other benefits, the time to first chemotherapy was a median of 50.6 months with ribociclib versus 38.9 months with placebo, so patients “had an extra year of delay before chemotherapy was utilized,” he said.
In general, Dr. Abuin said, we “see a consistent benefit with CDK 4/6 inhibitors in metastatic breast cancer across different settings.”
However, “it’s a little intriguing” that in a subgroup analysis of non–de novo disease, the overall survival benefit with ribociclib had a hazard ratio of 0.91, whereas the progression-free survival benefit was robust and statistically significant in an earlier report.
“This has been an important question, but I would caution all of us not to make too much out of the forest plot,” Dr. Hortobagyi said.
“There are a number of hypotheses one could come up with that could explain why the de novo and non–de novo populations faired differently in overall survival as opposed to progression-free survival, but there is also the simple possibility that this is a statistical fluke,” he said.
“We are in the process of analyzing this particular observation. In the meantime, I think we should just take the overall survival results of the entire population as the lead answer, and not follow the subgroup analysis until further information is available,” Dr. Hortobagyi said.
No new ribociclib safety signals were observed in the trial. The most common adverse events were neutropenia and liver function abnormalities, but they were “largely asymptomatic laboratory findings and completely reversible,” he said.
Twice as many patients treated with ribociclib developed prolonged QT intervals, but again, “no clinical consequences of this EKG finding were detected,” Dr. Hortobagyi said.
Less than 1% of patients in the ribociclib arm developed interstitial lung disease. The majority of safety events occurred in the first 12 months of treatment.
The work was funded by Novartis, maker of both ribociclib and letrozole. Dr. Hortobagyi reported receiving an institutional grant from the company and personal fees related to the trial. Other investigators disclosed ties to Novartis. Dr. Abuin reported relationships with many companies, including Novartis.
This article was updated 9/24/21.
“Based on these results, ribociclib and letrozole should be considered the preferred treatment option,” said lead investigator Gabriel N. Hortobagyi, MD, a breast cancer medical oncologist at the University of Texas MD Anderson Cancer Center, Houston.
He presented the definitive overall survival results from MONALESSA-2 which randomized 668 patients equally and in the first line to either ribociclib or placebo on a background of standard dose letrozole.
At a median follow up of 6.6 years, median overall survival with ribociclib was 63.9 months versus 51.4 months in the placebo arm, a 24% reduction in the relative risk of death (P = .004).
It was the first report of a median overall survival (OS) exceeding 5 years in a phase 3 trial for advanced breast cancer. The estimated 6-year OS rate was 44.2% for ribociclib versus 32.0% with placebo.
“These are really impressive results” and support the use of CDK 4/6 inhibitors in the front-line setting,” said study discussant Gonzalo Gomez Abuin, MD, a medical oncologist at Hospital Alemán in Bueno Aires.
Ribociclib and other CDK 4/6 inhibitors have shown consistent progression-free survival benefit for metastatic disease, but ribociclib is the first of the major phase 3 trials with definitive overall survival results. They have “been long awaited,” Dr. Abuin said.
The overall survival benefit in MONALESSA-2 began to emerge at around 20 months and continued to increase over time.
Women had no prior CDK4/6 inhibitor treatment, chemotherapy, or endocrine therapy for metastatic disease. “They represented a pure first-line population,” Dr. Hortobagyi said.
Among other benefits, the time to first chemotherapy was a median of 50.6 months with ribociclib versus 38.9 months with placebo, so patients “had an extra year of delay before chemotherapy was utilized,” he said.
In general, Dr. Abuin said, we “see a consistent benefit with CDK 4/6 inhibitors in metastatic breast cancer across different settings.”
However, “it’s a little intriguing” that in a subgroup analysis of non–de novo disease, the overall survival benefit with ribociclib had a hazard ratio of 0.91, whereas the progression-free survival benefit was robust and statistically significant in an earlier report.
“This has been an important question, but I would caution all of us not to make too much out of the forest plot,” Dr. Hortobagyi said.
“There are a number of hypotheses one could come up with that could explain why the de novo and non–de novo populations faired differently in overall survival as opposed to progression-free survival, but there is also the simple possibility that this is a statistical fluke,” he said.
“We are in the process of analyzing this particular observation. In the meantime, I think we should just take the overall survival results of the entire population as the lead answer, and not follow the subgroup analysis until further information is available,” Dr. Hortobagyi said.
No new ribociclib safety signals were observed in the trial. The most common adverse events were neutropenia and liver function abnormalities, but they were “largely asymptomatic laboratory findings and completely reversible,” he said.
Twice as many patients treated with ribociclib developed prolonged QT intervals, but again, “no clinical consequences of this EKG finding were detected,” Dr. Hortobagyi said.
Less than 1% of patients in the ribociclib arm developed interstitial lung disease. The majority of safety events occurred in the first 12 months of treatment.
The work was funded by Novartis, maker of both ribociclib and letrozole. Dr. Hortobagyi reported receiving an institutional grant from the company and personal fees related to the trial. Other investigators disclosed ties to Novartis. Dr. Abuin reported relationships with many companies, including Novartis.
This article was updated 9/24/21.
“Based on these results, ribociclib and letrozole should be considered the preferred treatment option,” said lead investigator Gabriel N. Hortobagyi, MD, a breast cancer medical oncologist at the University of Texas MD Anderson Cancer Center, Houston.
He presented the definitive overall survival results from MONALESSA-2 which randomized 668 patients equally and in the first line to either ribociclib or placebo on a background of standard dose letrozole.
At a median follow up of 6.6 years, median overall survival with ribociclib was 63.9 months versus 51.4 months in the placebo arm, a 24% reduction in the relative risk of death (P = .004).
It was the first report of a median overall survival (OS) exceeding 5 years in a phase 3 trial for advanced breast cancer. The estimated 6-year OS rate was 44.2% for ribociclib versus 32.0% with placebo.
“These are really impressive results” and support the use of CDK 4/6 inhibitors in the front-line setting,” said study discussant Gonzalo Gomez Abuin, MD, a medical oncologist at Hospital Alemán in Bueno Aires.
Ribociclib and other CDK 4/6 inhibitors have shown consistent progression-free survival benefit for metastatic disease, but ribociclib is the first of the major phase 3 trials with definitive overall survival results. They have “been long awaited,” Dr. Abuin said.
The overall survival benefit in MONALESSA-2 began to emerge at around 20 months and continued to increase over time.
Women had no prior CDK4/6 inhibitor treatment, chemotherapy, or endocrine therapy for metastatic disease. “They represented a pure first-line population,” Dr. Hortobagyi said.
Among other benefits, the time to first chemotherapy was a median of 50.6 months with ribociclib versus 38.9 months with placebo, so patients “had an extra year of delay before chemotherapy was utilized,” he said.
In general, Dr. Abuin said, we “see a consistent benefit with CDK 4/6 inhibitors in metastatic breast cancer across different settings.”
However, “it’s a little intriguing” that in a subgroup analysis of non–de novo disease, the overall survival benefit with ribociclib had a hazard ratio of 0.91, whereas the progression-free survival benefit was robust and statistically significant in an earlier report.
“This has been an important question, but I would caution all of us not to make too much out of the forest plot,” Dr. Hortobagyi said.
“There are a number of hypotheses one could come up with that could explain why the de novo and non–de novo populations faired differently in overall survival as opposed to progression-free survival, but there is also the simple possibility that this is a statistical fluke,” he said.
“We are in the process of analyzing this particular observation. In the meantime, I think we should just take the overall survival results of the entire population as the lead answer, and not follow the subgroup analysis until further information is available,” Dr. Hortobagyi said.
No new ribociclib safety signals were observed in the trial. The most common adverse events were neutropenia and liver function abnormalities, but they were “largely asymptomatic laboratory findings and completely reversible,” he said.
Twice as many patients treated with ribociclib developed prolonged QT intervals, but again, “no clinical consequences of this EKG finding were detected,” Dr. Hortobagyi said.
Less than 1% of patients in the ribociclib arm developed interstitial lung disease. The majority of safety events occurred in the first 12 months of treatment.
The work was funded by Novartis, maker of both ribociclib and letrozole. Dr. Hortobagyi reported receiving an institutional grant from the company and personal fees related to the trial. Other investigators disclosed ties to Novartis. Dr. Abuin reported relationships with many companies, including Novartis.
This article was updated 9/24/21.
FROM ESMO 2021
Durvalumab combos beat monotherapy for unresectable stage 3 NSCLC
Both combinations – durvalumab plus either the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A mAb monalizumab – also numerically improved objective response rate. “Safety profiles were consistent across arms and no new safety signals were identified,” said Alexandre Martinez-Marti, MD, the lead investigator on the phase 2 trial, dubbed COAST, which he presented (abstract LBA42) at the 2021 European Society for Medical Oncology Congress on Sept. 17.
“These data support further evaluations of these combinations,” said Dr. Martinez-Marti, also a thoracic medical oncologist at the Vall d’Hebron Institute of Oncology in Barcelona.
Durvalumab is already established as a standard of care option for patients with unresectable stage 3 NSCLC who don’t progress after concurrent chemoradiation. There’s been preliminary data suggesting the benefits might be greater with oleclumab or monalizumab, so the study team looked into the issue.
They randomized 66 patients with unresectable stage 3 NSCLC and no progression after chemoradiotherapy to durvalumab 1,500 mg IV every 4 weeks; 59 others to durvalumab at the same dosage plus oleclumab 3,000 mg IV every 2 weeks for the first two cycles then every 4 weeks, and 61 were randomized to durvalumab plus monalizumab 750 mg IV every 2 weeks.
Patients were treated for up to 12 months, and they started treatment no later than 42 days after completing chemoradiation.
Over a median follow-up of 11.5 months, median progression-free survival (PFS) was 6.3 months in the durvalumab arm, but 15.1 months with the monalizumab combination (PFS hazard ratio versus durvalumab alone, 0.65; 95% CI, 0.49-0.85), and not reached in the oleclumab arm (PFS HR, 0.44; 95% CI, 0.26-0.75).
There were only a few complete responders across the study groups. Partial responses rates were 22.4% of the durvalumab alone arm, 36.7% in the oleclumab group, and 32.3% in the monalizumab arm.
The investigator assessed objective response rate was 25.4% with durvalumab alone, 38.3% in the oleclumab group, and 37.1% with the monalizumab combination. Curves started to separate from durvalumab monotherapy at around 2-4 months.
“Overall, the safety profiles of the two combinations were generally similar to the safety profile of durvalumab alone,” Dr. Martinez-Marti said. The rate of grade 3 or higher treatment-emergent events incidence was 39.4% with durvalumab, 40.7% the oleclumab combination, and 27.9% with monalizumab.
The most common grade 3/4 events were pneumonia (5.9%) and decreased lymphocyte count (3.2%); both were less common with the monalizumab combination.
Combined rates of pneumonitis and radiation pneumonitis of any grade were 21.2% with durvalumab, 28.8% in the oleclumab group, and 21.3% with monalizumab.
The groups were generally well balanced at baseline. The majority of subjects were men, White, and former smokers. Most subjects had stage 3A or 3B disease.
The work was funded by AstraZeneca. The investigators disclosed numerous ties to the company, including Dr. Martinez-Marti, who reported personal fees, travel expenses, and other connections.
This article was updated 9/24/21.
Both combinations – durvalumab plus either the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A mAb monalizumab – also numerically improved objective response rate. “Safety profiles were consistent across arms and no new safety signals were identified,” said Alexandre Martinez-Marti, MD, the lead investigator on the phase 2 trial, dubbed COAST, which he presented (abstract LBA42) at the 2021 European Society for Medical Oncology Congress on Sept. 17.
“These data support further evaluations of these combinations,” said Dr. Martinez-Marti, also a thoracic medical oncologist at the Vall d’Hebron Institute of Oncology in Barcelona.
Durvalumab is already established as a standard of care option for patients with unresectable stage 3 NSCLC who don’t progress after concurrent chemoradiation. There’s been preliminary data suggesting the benefits might be greater with oleclumab or monalizumab, so the study team looked into the issue.
They randomized 66 patients with unresectable stage 3 NSCLC and no progression after chemoradiotherapy to durvalumab 1,500 mg IV every 4 weeks; 59 others to durvalumab at the same dosage plus oleclumab 3,000 mg IV every 2 weeks for the first two cycles then every 4 weeks, and 61 were randomized to durvalumab plus monalizumab 750 mg IV every 2 weeks.
Patients were treated for up to 12 months, and they started treatment no later than 42 days after completing chemoradiation.
Over a median follow-up of 11.5 months, median progression-free survival (PFS) was 6.3 months in the durvalumab arm, but 15.1 months with the monalizumab combination (PFS hazard ratio versus durvalumab alone, 0.65; 95% CI, 0.49-0.85), and not reached in the oleclumab arm (PFS HR, 0.44; 95% CI, 0.26-0.75).
There were only a few complete responders across the study groups. Partial responses rates were 22.4% of the durvalumab alone arm, 36.7% in the oleclumab group, and 32.3% in the monalizumab arm.
The investigator assessed objective response rate was 25.4% with durvalumab alone, 38.3% in the oleclumab group, and 37.1% with the monalizumab combination. Curves started to separate from durvalumab monotherapy at around 2-4 months.
“Overall, the safety profiles of the two combinations were generally similar to the safety profile of durvalumab alone,” Dr. Martinez-Marti said. The rate of grade 3 or higher treatment-emergent events incidence was 39.4% with durvalumab, 40.7% the oleclumab combination, and 27.9% with monalizumab.
The most common grade 3/4 events were pneumonia (5.9%) and decreased lymphocyte count (3.2%); both were less common with the monalizumab combination.
Combined rates of pneumonitis and radiation pneumonitis of any grade were 21.2% with durvalumab, 28.8% in the oleclumab group, and 21.3% with monalizumab.
The groups were generally well balanced at baseline. The majority of subjects were men, White, and former smokers. Most subjects had stage 3A or 3B disease.
The work was funded by AstraZeneca. The investigators disclosed numerous ties to the company, including Dr. Martinez-Marti, who reported personal fees, travel expenses, and other connections.
This article was updated 9/24/21.
Both combinations – durvalumab plus either the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A mAb monalizumab – also numerically improved objective response rate. “Safety profiles were consistent across arms and no new safety signals were identified,” said Alexandre Martinez-Marti, MD, the lead investigator on the phase 2 trial, dubbed COAST, which he presented (abstract LBA42) at the 2021 European Society for Medical Oncology Congress on Sept. 17.
“These data support further evaluations of these combinations,” said Dr. Martinez-Marti, also a thoracic medical oncologist at the Vall d’Hebron Institute of Oncology in Barcelona.
Durvalumab is already established as a standard of care option for patients with unresectable stage 3 NSCLC who don’t progress after concurrent chemoradiation. There’s been preliminary data suggesting the benefits might be greater with oleclumab or monalizumab, so the study team looked into the issue.
They randomized 66 patients with unresectable stage 3 NSCLC and no progression after chemoradiotherapy to durvalumab 1,500 mg IV every 4 weeks; 59 others to durvalumab at the same dosage plus oleclumab 3,000 mg IV every 2 weeks for the first two cycles then every 4 weeks, and 61 were randomized to durvalumab plus monalizumab 750 mg IV every 2 weeks.
Patients were treated for up to 12 months, and they started treatment no later than 42 days after completing chemoradiation.
Over a median follow-up of 11.5 months, median progression-free survival (PFS) was 6.3 months in the durvalumab arm, but 15.1 months with the monalizumab combination (PFS hazard ratio versus durvalumab alone, 0.65; 95% CI, 0.49-0.85), and not reached in the oleclumab arm (PFS HR, 0.44; 95% CI, 0.26-0.75).
There were only a few complete responders across the study groups. Partial responses rates were 22.4% of the durvalumab alone arm, 36.7% in the oleclumab group, and 32.3% in the monalizumab arm.
The investigator assessed objective response rate was 25.4% with durvalumab alone, 38.3% in the oleclumab group, and 37.1% with the monalizumab combination. Curves started to separate from durvalumab monotherapy at around 2-4 months.
“Overall, the safety profiles of the two combinations were generally similar to the safety profile of durvalumab alone,” Dr. Martinez-Marti said. The rate of grade 3 or higher treatment-emergent events incidence was 39.4% with durvalumab, 40.7% the oleclumab combination, and 27.9% with monalizumab.
The most common grade 3/4 events were pneumonia (5.9%) and decreased lymphocyte count (3.2%); both were less common with the monalizumab combination.
Combined rates of pneumonitis and radiation pneumonitis of any grade were 21.2% with durvalumab, 28.8% in the oleclumab group, and 21.3% with monalizumab.
The groups were generally well balanced at baseline. The majority of subjects were men, White, and former smokers. Most subjects had stage 3A or 3B disease.
The work was funded by AstraZeneca. The investigators disclosed numerous ties to the company, including Dr. Martinez-Marti, who reported personal fees, travel expenses, and other connections.
This article was updated 9/24/21.
FROM ESMO CONGRESS 2021
Mediastinal relapse risk lower with PORT, but no survival benefit
The report was an update on the LungART international clinical trial, which, at the 2020 ESMO meeting, was shown not to improve disease-free survival over the course of 3 years. The update showed that, in addition to the lack of disease-free survival benefit, there was also no difference in metastases, and patients randomized to PORT had higher rates of death and grade 3/4 cardiopulmonary toxicity. The investigators returned this year to expand on another finding from the trial, a 51% reduction in the risk of mediastinal relapse with postoperative radiotherapy. The new analysis suggests there might still be a role for PORT in select patients, perhaps those with heavy nodal involvement, said lead investigator and presenter Cecile Le Pechoux, MD, radiation oncologist at the Gustave Roussy cancer treatment center in Villejuif, France.
For now, “personalized prescription of PORT should be based on prognostic factors of relapse and joint assessment of toxicity and efficacy,” she said.
Study discussant Pilar Garrido, MD, PhD, head of thoracic tumors Ramon y Cajal University Hospital, Madrid, agreed that there might still be a benefit for people with multiple N2 nodal station involvement, but at present, she said, “for me PORT cannot be the standard of care ... given the toxicity and mortality among PORT patients in LungART.”
The trial randomized 501 patients with non–small cell lung cancer with mediastinal involvement to either PORT at 54 Gy over 5.5 weeks or no further treatment following complete resection. Neoadjuvant or adjuvant chemotherapy were allowed.
The 3-year mediastinal relapse-free survival was 72.26% in the control arm but 86.06% with PORT (hazard ratio, 0.45; 95% confidence interval, 0.3-0.69).
“There is a significant difference” when it comes to mediastinal relapse, and “patients who have PORT do better. If we look at the location of mediastinal relapse, most [patients] relapse within the initially involved node. This is important information,” Dr. Le Pechoux said.
For left-sided tumors, the most frequent sites of mediastinal relapse were thoracic lymph node stations 7, 4L, and 4R. For right sided tumors, the most frequent stations were 4R, 2R and 7.
Prognostic factors for disease-free survival included quality of resection, extent of mediastinal involvement, and lymph node ratio (involved/explored). Nodal involvement was a significant prognostic factor for overall survival, but PORT was not (HR, 0.98; 95% CI, 0.7-1.4).
Mediastinal involvement with more than two node stations and less than an RO, or microscopically margin-negative resection, increased the risk of relapse.
The work was funded by the French National Cancer Institute, French Health Ministry, Institute Gustave Roussy, and Cancer Research UK. Dr. Pechoux and Dr. Garido disclosed ties to AstraZeneca, Roche, Amgen, and other companies.
This article was updated 9/24/21.
The report was an update on the LungART international clinical trial, which, at the 2020 ESMO meeting, was shown not to improve disease-free survival over the course of 3 years. The update showed that, in addition to the lack of disease-free survival benefit, there was also no difference in metastases, and patients randomized to PORT had higher rates of death and grade 3/4 cardiopulmonary toxicity. The investigators returned this year to expand on another finding from the trial, a 51% reduction in the risk of mediastinal relapse with postoperative radiotherapy. The new analysis suggests there might still be a role for PORT in select patients, perhaps those with heavy nodal involvement, said lead investigator and presenter Cecile Le Pechoux, MD, radiation oncologist at the Gustave Roussy cancer treatment center in Villejuif, France.
For now, “personalized prescription of PORT should be based on prognostic factors of relapse and joint assessment of toxicity and efficacy,” she said.
Study discussant Pilar Garrido, MD, PhD, head of thoracic tumors Ramon y Cajal University Hospital, Madrid, agreed that there might still be a benefit for people with multiple N2 nodal station involvement, but at present, she said, “for me PORT cannot be the standard of care ... given the toxicity and mortality among PORT patients in LungART.”
The trial randomized 501 patients with non–small cell lung cancer with mediastinal involvement to either PORT at 54 Gy over 5.5 weeks or no further treatment following complete resection. Neoadjuvant or adjuvant chemotherapy were allowed.
The 3-year mediastinal relapse-free survival was 72.26% in the control arm but 86.06% with PORT (hazard ratio, 0.45; 95% confidence interval, 0.3-0.69).
“There is a significant difference” when it comes to mediastinal relapse, and “patients who have PORT do better. If we look at the location of mediastinal relapse, most [patients] relapse within the initially involved node. This is important information,” Dr. Le Pechoux said.
For left-sided tumors, the most frequent sites of mediastinal relapse were thoracic lymph node stations 7, 4L, and 4R. For right sided tumors, the most frequent stations were 4R, 2R and 7.
Prognostic factors for disease-free survival included quality of resection, extent of mediastinal involvement, and lymph node ratio (involved/explored). Nodal involvement was a significant prognostic factor for overall survival, but PORT was not (HR, 0.98; 95% CI, 0.7-1.4).
Mediastinal involvement with more than two node stations and less than an RO, or microscopically margin-negative resection, increased the risk of relapse.
The work was funded by the French National Cancer Institute, French Health Ministry, Institute Gustave Roussy, and Cancer Research UK. Dr. Pechoux and Dr. Garido disclosed ties to AstraZeneca, Roche, Amgen, and other companies.
This article was updated 9/24/21.
The report was an update on the LungART international clinical trial, which, at the 2020 ESMO meeting, was shown not to improve disease-free survival over the course of 3 years. The update showed that, in addition to the lack of disease-free survival benefit, there was also no difference in metastases, and patients randomized to PORT had higher rates of death and grade 3/4 cardiopulmonary toxicity. The investigators returned this year to expand on another finding from the trial, a 51% reduction in the risk of mediastinal relapse with postoperative radiotherapy. The new analysis suggests there might still be a role for PORT in select patients, perhaps those with heavy nodal involvement, said lead investigator and presenter Cecile Le Pechoux, MD, radiation oncologist at the Gustave Roussy cancer treatment center in Villejuif, France.
For now, “personalized prescription of PORT should be based on prognostic factors of relapse and joint assessment of toxicity and efficacy,” she said.
Study discussant Pilar Garrido, MD, PhD, head of thoracic tumors Ramon y Cajal University Hospital, Madrid, agreed that there might still be a benefit for people with multiple N2 nodal station involvement, but at present, she said, “for me PORT cannot be the standard of care ... given the toxicity and mortality among PORT patients in LungART.”
The trial randomized 501 patients with non–small cell lung cancer with mediastinal involvement to either PORT at 54 Gy over 5.5 weeks or no further treatment following complete resection. Neoadjuvant or adjuvant chemotherapy were allowed.
The 3-year mediastinal relapse-free survival was 72.26% in the control arm but 86.06% with PORT (hazard ratio, 0.45; 95% confidence interval, 0.3-0.69).
“There is a significant difference” when it comes to mediastinal relapse, and “patients who have PORT do better. If we look at the location of mediastinal relapse, most [patients] relapse within the initially involved node. This is important information,” Dr. Le Pechoux said.
For left-sided tumors, the most frequent sites of mediastinal relapse were thoracic lymph node stations 7, 4L, and 4R. For right sided tumors, the most frequent stations were 4R, 2R and 7.
Prognostic factors for disease-free survival included quality of resection, extent of mediastinal involvement, and lymph node ratio (involved/explored). Nodal involvement was a significant prognostic factor for overall survival, but PORT was not (HR, 0.98; 95% CI, 0.7-1.4).
Mediastinal involvement with more than two node stations and less than an RO, or microscopically margin-negative resection, increased the risk of relapse.
The work was funded by the French National Cancer Institute, French Health Ministry, Institute Gustave Roussy, and Cancer Research UK. Dr. Pechoux and Dr. Garido disclosed ties to AstraZeneca, Roche, Amgen, and other companies.
This article was updated 9/24/21.
FROM ESMO CONGRESS 2021
COVID is especially dangerous for mesothelioma
according to Susana Cedres, MD, PhD, a thoracic medical oncologist at Vall d’Hebron University Hospital, Barcelona.
At the annual World Conference on Lung Cancer, she reported on her institution’s experience during the first year of the pandemic before widespread vaccine rollouts.
Among 38 malignant pleural mesothelioma (MPM) patients, seven (18%) patients were diagnosed with COVID-19 and of these, three patients were asymptomatic, four (57%) died of complications including bilateral pneumonia within a median of less than half a month after diagnosis, and a fifth patient died from MPM progression.
The findings confirm the particular risk of COVID in MPM. According to researchers reporting in Scientific Reports, mesothelioma was the only cancer linked to significantly worse outcomes. Other risks included tuberculosis, drug use, hepatitis, HIV/AIDS, cardiomyopathy, and diabetes.
However, the Barcelona report only has seven patients, and it’s one of only a few to address the specifics of COVID in MPM.
“There really is a need for more inclusion of MPM patients in international [COVID] registries” to better characterize the course of infection and improve outcomes, said study discussant Francoise Galateau-Salle, MD, PhD, a mesothelioma expert at the Cancer Center Leon Berard in Lyon, France.
Among the seven positive cases in Barcelona, almost all had comorbidities, with the most common being cardiovascular disease in four patients (57%). Only two patients (29%) were on oncologic treatment at the time they were diagnosed, and the median age at diagnosis was 62 years. Four cases were in men, three in women. MPM stage was not reported.
WCLC 2021 was organized by the International Association for the Study of Lung Cancer.
No funding source was reported. Dr. Cedres is an adviser and/or reported travel expenses from a number of companies, including Merck, Pfizer, and Bristol-Myers Squibb. Dr. Galateau-Salle had no disclosures.
according to Susana Cedres, MD, PhD, a thoracic medical oncologist at Vall d’Hebron University Hospital, Barcelona.
At the annual World Conference on Lung Cancer, she reported on her institution’s experience during the first year of the pandemic before widespread vaccine rollouts.
Among 38 malignant pleural mesothelioma (MPM) patients, seven (18%) patients were diagnosed with COVID-19 and of these, three patients were asymptomatic, four (57%) died of complications including bilateral pneumonia within a median of less than half a month after diagnosis, and a fifth patient died from MPM progression.
The findings confirm the particular risk of COVID in MPM. According to researchers reporting in Scientific Reports, mesothelioma was the only cancer linked to significantly worse outcomes. Other risks included tuberculosis, drug use, hepatitis, HIV/AIDS, cardiomyopathy, and diabetes.
However, the Barcelona report only has seven patients, and it’s one of only a few to address the specifics of COVID in MPM.
“There really is a need for more inclusion of MPM patients in international [COVID] registries” to better characterize the course of infection and improve outcomes, said study discussant Francoise Galateau-Salle, MD, PhD, a mesothelioma expert at the Cancer Center Leon Berard in Lyon, France.
Among the seven positive cases in Barcelona, almost all had comorbidities, with the most common being cardiovascular disease in four patients (57%). Only two patients (29%) were on oncologic treatment at the time they were diagnosed, and the median age at diagnosis was 62 years. Four cases were in men, three in women. MPM stage was not reported.
WCLC 2021 was organized by the International Association for the Study of Lung Cancer.
No funding source was reported. Dr. Cedres is an adviser and/or reported travel expenses from a number of companies, including Merck, Pfizer, and Bristol-Myers Squibb. Dr. Galateau-Salle had no disclosures.
according to Susana Cedres, MD, PhD, a thoracic medical oncologist at Vall d’Hebron University Hospital, Barcelona.
At the annual World Conference on Lung Cancer, she reported on her institution’s experience during the first year of the pandemic before widespread vaccine rollouts.
Among 38 malignant pleural mesothelioma (MPM) patients, seven (18%) patients were diagnosed with COVID-19 and of these, three patients were asymptomatic, four (57%) died of complications including bilateral pneumonia within a median of less than half a month after diagnosis, and a fifth patient died from MPM progression.
The findings confirm the particular risk of COVID in MPM. According to researchers reporting in Scientific Reports, mesothelioma was the only cancer linked to significantly worse outcomes. Other risks included tuberculosis, drug use, hepatitis, HIV/AIDS, cardiomyopathy, and diabetes.
However, the Barcelona report only has seven patients, and it’s one of only a few to address the specifics of COVID in MPM.
“There really is a need for more inclusion of MPM patients in international [COVID] registries” to better characterize the course of infection and improve outcomes, said study discussant Francoise Galateau-Salle, MD, PhD, a mesothelioma expert at the Cancer Center Leon Berard in Lyon, France.
Among the seven positive cases in Barcelona, almost all had comorbidities, with the most common being cardiovascular disease in four patients (57%). Only two patients (29%) were on oncologic treatment at the time they were diagnosed, and the median age at diagnosis was 62 years. Four cases were in men, three in women. MPM stage was not reported.
WCLC 2021 was organized by the International Association for the Study of Lung Cancer.
No funding source was reported. Dr. Cedres is an adviser and/or reported travel expenses from a number of companies, including Merck, Pfizer, and Bristol-Myers Squibb. Dr. Galateau-Salle had no disclosures.
FROM WCLC 2021
Unequal resource distribution underlies lung cancer disparities
Lung cancer disparities are reversible, but it will take changes at the social policy and organizational levels to do it, according to Ray Osarogiagbon, MBBS, a medical oncologist in the thoracic oncology program at Baptist Cancer Center, Memphis.
Much of the issue comes down to unequal distribution of services across the country, with less high-end care available in areas hardest hit by lung cancer, which are often areas with higher percentages of Black people, Dr. Osarogiagbon said. He addressed the issues – which he conceptualizes as “avoidable differences” – in a plenary presentation at the virtual 2021 World Conference on Lung Cancer.
He said that much of disparity research has focused on patient-level issues, but it has the least potential to effect change and also has “the unpleasant side effect of stigmatizing the victims of disparate health care delivery.”
Better to look at the big picture. “We have to focus on the areas where we are most likely to be successful, the social policy level, next the organizational level, and then providers,” he said.
Kentucky, followed by Mississippi, Arkansas, Tennessee, West Virginia, and Alabama, has the highest lung cancer burden in the United States. While lung cancer has been on the decline for decades nationwide, some counties in those states in particular continue to struggle with rising lung cancer mortality.
Dr. Osarogiagbon’s own health care system, which serves western Tennessee as well as eastern Arkansas and northern Mississippi, sees about 1,300 lung cancer cases annually, more than many states in the United States.
Regional disparities in lung cancer care span the entirety of available services, from unequal access to tobacco cessation and other preventive measures straight through to access to leading-edge systemic therapies. Disparities are particularly acute with more recent advances such as immunotherapy and low-dose CT screening.
One recent study, for instance, found that several southern states with high lung cancer burdens had screening rates below 4%, while several New England states had rates ranging to over 15%.
“There is a mismatch between the places were lung cancer kills and the places where we have invested in low-dose CT scan facilities,” Dr. Osarogiagbon said. As a side effect, White patients have better access,
It’s not, he said, that Black people are more likely to refuse such services, as least as far as clinical trials go.
Black patients are significantly underrepresented in pharmaceutical industry trials. Part of the issues is that areas hardest hit by lung cancer are often also ones less likely to have the infrastructure to support trials.
But on an equal playing field, Black patients are at least as eager as White patients to sign up for a trial. Dr. Osarogiagbon and colleagues found that, if offered the chance, almost 60% of Black patients said they would participate in a trial versus 53.4% of White patients. If access were equal, there would be “no race-based disparities” in trial participation, he said.
It’s also emerging that Black patients might benefit more from innovations such as immune checkpoint inhibitors treatment and low-dose CT screening, which means that, if they were included in more trials, companies would likely have stronger study results.
It’s something they should pay attention to, if for no other reason than it would help their bottom line, Dr. Osarogiagbon said.
Curative surgery for early-stage lung tumors is another issue. At the county level in the United States, he and his team found that it’s offered to anywhere from 13% to 92% of patients who qualify.
“Counties in the lowest quartile for receipt of surgery were those with a high proportion of non-Hispanic Black subjects, high poverty and uninsured rates, low surgeon-to-population ratio, and nonmetropolitan status,” they found.
Dr. Osarogiagbon is a consultant for and/or has stock in a number of companies, including AstraZeneca, Eli Lilly, and Genentech.
Lung cancer disparities are reversible, but it will take changes at the social policy and organizational levels to do it, according to Ray Osarogiagbon, MBBS, a medical oncologist in the thoracic oncology program at Baptist Cancer Center, Memphis.
Much of the issue comes down to unequal distribution of services across the country, with less high-end care available in areas hardest hit by lung cancer, which are often areas with higher percentages of Black people, Dr. Osarogiagbon said. He addressed the issues – which he conceptualizes as “avoidable differences” – in a plenary presentation at the virtual 2021 World Conference on Lung Cancer.
He said that much of disparity research has focused on patient-level issues, but it has the least potential to effect change and also has “the unpleasant side effect of stigmatizing the victims of disparate health care delivery.”
Better to look at the big picture. “We have to focus on the areas where we are most likely to be successful, the social policy level, next the organizational level, and then providers,” he said.
Kentucky, followed by Mississippi, Arkansas, Tennessee, West Virginia, and Alabama, has the highest lung cancer burden in the United States. While lung cancer has been on the decline for decades nationwide, some counties in those states in particular continue to struggle with rising lung cancer mortality.
Dr. Osarogiagbon’s own health care system, which serves western Tennessee as well as eastern Arkansas and northern Mississippi, sees about 1,300 lung cancer cases annually, more than many states in the United States.
Regional disparities in lung cancer care span the entirety of available services, from unequal access to tobacco cessation and other preventive measures straight through to access to leading-edge systemic therapies. Disparities are particularly acute with more recent advances such as immunotherapy and low-dose CT screening.
One recent study, for instance, found that several southern states with high lung cancer burdens had screening rates below 4%, while several New England states had rates ranging to over 15%.
“There is a mismatch between the places were lung cancer kills and the places where we have invested in low-dose CT scan facilities,” Dr. Osarogiagbon said. As a side effect, White patients have better access,
It’s not, he said, that Black people are more likely to refuse such services, as least as far as clinical trials go.
Black patients are significantly underrepresented in pharmaceutical industry trials. Part of the issues is that areas hardest hit by lung cancer are often also ones less likely to have the infrastructure to support trials.
But on an equal playing field, Black patients are at least as eager as White patients to sign up for a trial. Dr. Osarogiagbon and colleagues found that, if offered the chance, almost 60% of Black patients said they would participate in a trial versus 53.4% of White patients. If access were equal, there would be “no race-based disparities” in trial participation, he said.
It’s also emerging that Black patients might benefit more from innovations such as immune checkpoint inhibitors treatment and low-dose CT screening, which means that, if they were included in more trials, companies would likely have stronger study results.
It’s something they should pay attention to, if for no other reason than it would help their bottom line, Dr. Osarogiagbon said.
Curative surgery for early-stage lung tumors is another issue. At the county level in the United States, he and his team found that it’s offered to anywhere from 13% to 92% of patients who qualify.
“Counties in the lowest quartile for receipt of surgery were those with a high proportion of non-Hispanic Black subjects, high poverty and uninsured rates, low surgeon-to-population ratio, and nonmetropolitan status,” they found.
Dr. Osarogiagbon is a consultant for and/or has stock in a number of companies, including AstraZeneca, Eli Lilly, and Genentech.
Lung cancer disparities are reversible, but it will take changes at the social policy and organizational levels to do it, according to Ray Osarogiagbon, MBBS, a medical oncologist in the thoracic oncology program at Baptist Cancer Center, Memphis.
Much of the issue comes down to unequal distribution of services across the country, with less high-end care available in areas hardest hit by lung cancer, which are often areas with higher percentages of Black people, Dr. Osarogiagbon said. He addressed the issues – which he conceptualizes as “avoidable differences” – in a plenary presentation at the virtual 2021 World Conference on Lung Cancer.
He said that much of disparity research has focused on patient-level issues, but it has the least potential to effect change and also has “the unpleasant side effect of stigmatizing the victims of disparate health care delivery.”
Better to look at the big picture. “We have to focus on the areas where we are most likely to be successful, the social policy level, next the organizational level, and then providers,” he said.
Kentucky, followed by Mississippi, Arkansas, Tennessee, West Virginia, and Alabama, has the highest lung cancer burden in the United States. While lung cancer has been on the decline for decades nationwide, some counties in those states in particular continue to struggle with rising lung cancer mortality.
Dr. Osarogiagbon’s own health care system, which serves western Tennessee as well as eastern Arkansas and northern Mississippi, sees about 1,300 lung cancer cases annually, more than many states in the United States.
Regional disparities in lung cancer care span the entirety of available services, from unequal access to tobacco cessation and other preventive measures straight through to access to leading-edge systemic therapies. Disparities are particularly acute with more recent advances such as immunotherapy and low-dose CT screening.
One recent study, for instance, found that several southern states with high lung cancer burdens had screening rates below 4%, while several New England states had rates ranging to over 15%.
“There is a mismatch between the places were lung cancer kills and the places where we have invested in low-dose CT scan facilities,” Dr. Osarogiagbon said. As a side effect, White patients have better access,
It’s not, he said, that Black people are more likely to refuse such services, as least as far as clinical trials go.
Black patients are significantly underrepresented in pharmaceutical industry trials. Part of the issues is that areas hardest hit by lung cancer are often also ones less likely to have the infrastructure to support trials.
But on an equal playing field, Black patients are at least as eager as White patients to sign up for a trial. Dr. Osarogiagbon and colleagues found that, if offered the chance, almost 60% of Black patients said they would participate in a trial versus 53.4% of White patients. If access were equal, there would be “no race-based disparities” in trial participation, he said.
It’s also emerging that Black patients might benefit more from innovations such as immune checkpoint inhibitors treatment and low-dose CT screening, which means that, if they were included in more trials, companies would likely have stronger study results.
It’s something they should pay attention to, if for no other reason than it would help their bottom line, Dr. Osarogiagbon said.
Curative surgery for early-stage lung tumors is another issue. At the county level in the United States, he and his team found that it’s offered to anywhere from 13% to 92% of patients who qualify.
“Counties in the lowest quartile for receipt of surgery were those with a high proportion of non-Hispanic Black subjects, high poverty and uninsured rates, low surgeon-to-population ratio, and nonmetropolitan status,” they found.
Dr. Osarogiagbon is a consultant for and/or has stock in a number of companies, including AstraZeneca, Eli Lilly, and Genentech.
FROM WCLC 2021
Finding the most bang for the buck with adjuvant atezolizumab for NSCLC
Investigators are zeroing in on the stage II-IIIa non–small cell lung cancer patients most likely to benefit from adjuvant atezolizumab (Tecentriq) following resection and chemotherapy.
It seems that PD-L1 positive patients, those who undergo lobectomy, those who have nodal involvement, and those treated with all common platinum doublets, with the possible exception of cisplatin-gemcitabine, are most likely to benefit from adjuvant treatment, according to a report at the virtual 2021 World Congress on Lung Cancer.
Results come for an analysis of IMpower010, which randomized 1,005 patients equally to either best supportive care or atezolizumab every 21 days for 16 cycles following resection and chemotherapy.
The topline results, reported recently, found a 34% improvement in disease-free survival (DFS) in stage II-IIIa patients expressing PD-L1 and a 21% improvement across all patients regardless of PD-L1 expression.
It was the first positive phase 3 trial for adjuvant immunotherapy in NSCLC. Maker Hoffman-La Roche subsequently applied to the U.S. Food and Drug Administration for an indication for adjuvant treatment following surgery and platinum-based chemotherapy for NSCLC with PD-L1 expression of at least 1%.
At the WCLC meeting, investigators took a closer look at IMpower010 to gauge the impact of different surgery and chemotherapy types on outcomes.
“Improved DFS was observed with adjuvant atezolizumab” for II-IIIa disease across most stages in patients “with nodal involvement, and across most surgery resection types and chemotherapy regimens,” said lead investigator Nasser Altorki, MD, director of the division of thoracic surgery at New York Presbyterian-Weill Cornell Medical Center in New York.
Study discussant Ichiro Yoshino, MD, PhD, a thoracic surgeon at Chiba University, in Japan, expanded on the “most” part of the assertion.
“Patients who underwent lobectomy [78%] had more evident benefit. … Patients who had a pneumonectomy [16%] did not benefit from atezolizumab,” he said (DFS hazard ratio, 0.91, 95% confidence interval, 0.56-1.47).
The reasons are unclear. It could be because patients who have pneumonectomies are less tolerant of adjuvant chemotherapy, so might have not gotten complete courses, but whatever the cause, Dr. Yoshino said it’s an important finding that needs further investigation.
Also, there was no DFS benefit in the 16% of patients who received cisplatin-gemcitabine for chemotherapy instead of other platinum doublets (HR, 0.94, 95% CI, 0.56-1.57).
It might have to do with the fact that under 80% of cisplatin-gemcitabine patients completed all four cycles of chemotherapy versus completion rates of up to more than 90% with other platinum doublets. It might also, however, have something to do with the way gemcitabine works or its interaction with atezolizumab.
The issue is another one that needs “to be examined,” Dr. Yoshino said.
The trial was funded by Hoffman-La Roche. Dr. Altorki is an advisor and/or researcher for AstraZeneca, Merck, and Johnson & Johnson. Among various company ties, Dr. Yoshino is an advisor and speaker for AstraZeneca and Johnson & Johnson and a researcher for Pfizer.
Investigators are zeroing in on the stage II-IIIa non–small cell lung cancer patients most likely to benefit from adjuvant atezolizumab (Tecentriq) following resection and chemotherapy.
It seems that PD-L1 positive patients, those who undergo lobectomy, those who have nodal involvement, and those treated with all common platinum doublets, with the possible exception of cisplatin-gemcitabine, are most likely to benefit from adjuvant treatment, according to a report at the virtual 2021 World Congress on Lung Cancer.
Results come for an analysis of IMpower010, which randomized 1,005 patients equally to either best supportive care or atezolizumab every 21 days for 16 cycles following resection and chemotherapy.
The topline results, reported recently, found a 34% improvement in disease-free survival (DFS) in stage II-IIIa patients expressing PD-L1 and a 21% improvement across all patients regardless of PD-L1 expression.
It was the first positive phase 3 trial for adjuvant immunotherapy in NSCLC. Maker Hoffman-La Roche subsequently applied to the U.S. Food and Drug Administration for an indication for adjuvant treatment following surgery and platinum-based chemotherapy for NSCLC with PD-L1 expression of at least 1%.
At the WCLC meeting, investigators took a closer look at IMpower010 to gauge the impact of different surgery and chemotherapy types on outcomes.
“Improved DFS was observed with adjuvant atezolizumab” for II-IIIa disease across most stages in patients “with nodal involvement, and across most surgery resection types and chemotherapy regimens,” said lead investigator Nasser Altorki, MD, director of the division of thoracic surgery at New York Presbyterian-Weill Cornell Medical Center in New York.
Study discussant Ichiro Yoshino, MD, PhD, a thoracic surgeon at Chiba University, in Japan, expanded on the “most” part of the assertion.
“Patients who underwent lobectomy [78%] had more evident benefit. … Patients who had a pneumonectomy [16%] did not benefit from atezolizumab,” he said (DFS hazard ratio, 0.91, 95% confidence interval, 0.56-1.47).
The reasons are unclear. It could be because patients who have pneumonectomies are less tolerant of adjuvant chemotherapy, so might have not gotten complete courses, but whatever the cause, Dr. Yoshino said it’s an important finding that needs further investigation.
Also, there was no DFS benefit in the 16% of patients who received cisplatin-gemcitabine for chemotherapy instead of other platinum doublets (HR, 0.94, 95% CI, 0.56-1.57).
It might have to do with the fact that under 80% of cisplatin-gemcitabine patients completed all four cycles of chemotherapy versus completion rates of up to more than 90% with other platinum doublets. It might also, however, have something to do with the way gemcitabine works or its interaction with atezolizumab.
The issue is another one that needs “to be examined,” Dr. Yoshino said.
The trial was funded by Hoffman-La Roche. Dr. Altorki is an advisor and/or researcher for AstraZeneca, Merck, and Johnson & Johnson. Among various company ties, Dr. Yoshino is an advisor and speaker for AstraZeneca and Johnson & Johnson and a researcher for Pfizer.
Investigators are zeroing in on the stage II-IIIa non–small cell lung cancer patients most likely to benefit from adjuvant atezolizumab (Tecentriq) following resection and chemotherapy.
It seems that PD-L1 positive patients, those who undergo lobectomy, those who have nodal involvement, and those treated with all common platinum doublets, with the possible exception of cisplatin-gemcitabine, are most likely to benefit from adjuvant treatment, according to a report at the virtual 2021 World Congress on Lung Cancer.
Results come for an analysis of IMpower010, which randomized 1,005 patients equally to either best supportive care or atezolizumab every 21 days for 16 cycles following resection and chemotherapy.
The topline results, reported recently, found a 34% improvement in disease-free survival (DFS) in stage II-IIIa patients expressing PD-L1 and a 21% improvement across all patients regardless of PD-L1 expression.
It was the first positive phase 3 trial for adjuvant immunotherapy in NSCLC. Maker Hoffman-La Roche subsequently applied to the U.S. Food and Drug Administration for an indication for adjuvant treatment following surgery and platinum-based chemotherapy for NSCLC with PD-L1 expression of at least 1%.
At the WCLC meeting, investigators took a closer look at IMpower010 to gauge the impact of different surgery and chemotherapy types on outcomes.
“Improved DFS was observed with adjuvant atezolizumab” for II-IIIa disease across most stages in patients “with nodal involvement, and across most surgery resection types and chemotherapy regimens,” said lead investigator Nasser Altorki, MD, director of the division of thoracic surgery at New York Presbyterian-Weill Cornell Medical Center in New York.
Study discussant Ichiro Yoshino, MD, PhD, a thoracic surgeon at Chiba University, in Japan, expanded on the “most” part of the assertion.
“Patients who underwent lobectomy [78%] had more evident benefit. … Patients who had a pneumonectomy [16%] did not benefit from atezolizumab,” he said (DFS hazard ratio, 0.91, 95% confidence interval, 0.56-1.47).
The reasons are unclear. It could be because patients who have pneumonectomies are less tolerant of adjuvant chemotherapy, so might have not gotten complete courses, but whatever the cause, Dr. Yoshino said it’s an important finding that needs further investigation.
Also, there was no DFS benefit in the 16% of patients who received cisplatin-gemcitabine for chemotherapy instead of other platinum doublets (HR, 0.94, 95% CI, 0.56-1.57).
It might have to do with the fact that under 80% of cisplatin-gemcitabine patients completed all four cycles of chemotherapy versus completion rates of up to more than 90% with other platinum doublets. It might also, however, have something to do with the way gemcitabine works or its interaction with atezolizumab.
The issue is another one that needs “to be examined,” Dr. Yoshino said.
The trial was funded by Hoffman-La Roche. Dr. Altorki is an advisor and/or researcher for AstraZeneca, Merck, and Johnson & Johnson. Among various company ties, Dr. Yoshino is an advisor and speaker for AstraZeneca and Johnson & Johnson and a researcher for Pfizer.
FROM WCLC 2021
Study calls higher surgery costs at NCI centers into question
according to a recent report in JAMA Network Open.
“While acceptable to pay higher prices for care that is expected to be of higher quality, we found no differences in short-term postsurgical outcomes,” said authors led by Samuel Takvorian, MD, a medical oncologist at the University of Pennsylvania, Philadelphia.
The team looked at what insurance companies paid for incident breast, colon, and lung cancer surgeries, which together account for most cancer surgeries, among 66,878 patients treated from 2011 to 2014 at almost 3,000 U.S. hospitals.
Three-quarters had surgery at a community hospital, and 8.3% were treated at one of the nation’s 71 NCI centers, which are recognized by the NCI as meeting rigorous standards in cancer care. The remaining patients were treated at non-NCI academic hospitals.
The mean surgery-specific insurer prices paid at NCI centers was $18,526 versus $14,772 at community hospitals, a difference of $3,755 (P < .001) that was driven primarily by higher facility payments at NCI centers, a mean of $17,704 versus $14,120 at community hospitals.
Mean 90-day postdischarge payments were also $5,744 higher at NCI centers, $47,035 versus $41,291 at community hospitals (P = .006).
The team used postsurgical acute care utilization as a marker of quality but found no differences between the two settings. Mean length of stay was 5.1 days and the probability of ED utilization just over 13% in both, and both had a 90-day readmission rate of just over 10%.
Who should be treated at an NCI center?
The data didn’t allow for direct comparison of surgical quality, such as margin status, number of lymph nodes assessed, or postoperative complications, but the postsurgery utilization outcomes “suggest that quality may have been similar,” said Nancy Keating, MD, a health care policy and medicine professor at Harvard Medical School, Boston, in an invited commentary.
The price differences are probably because NCI centers, with their comprehensive offerings, market share, and prestige, can negotiate higher reimbursement rates from insurers, the researchers said.
There is also evidence of better outcomes at NCI centers, particularly for more advanced and complex cases. However, “this study focused on common cancer surgical procedures ... revealing that there is a premium associated with receipt of surgical cancer care at NCI centers.” Further research “is necessary to judge whether and under what circumstances the premium price of NCI centers is justified,” the investigators said.
Dr. Keating noted that “it is likely that some patients benefit from the highly specialized care available at NCI-designated cancer centers ... but it is also likely that many other patients will do equally well regardless of where they receive their care.”
Amid ever-increasing cancer care costs and the need to strategically allocate financial resources, more research is needed to “identify subgroups of patients for whom highly specialized care is particularly necessary to achieve better outcomes. Such data could also be used by payers considering tiered networks and by physician organizations participating in risk contracts for decisions about where to refer patients with cancer for treatment,” she said.
Rectifying a ‘misalignment’
The researchers also said the findings reveal competing incentives, with commercial payers wanting to steer patients away from high-cost hospitals but health systems hoping to maximize surgical volume at lucrative referral centers.
“Value-based or bundled payment reimbursement for surgical episodes, particularly when paired with mandatory reporting on surgical outcomes, could help to rectify this misalignment,” they said.
Out-of-pocket spending wasn’t analyzed in the study, so it’s unknown how the higher prices at NCI centers hit patients in the pocketbook.
Meanwhile, non-NCI academic hospitals also had higher insurer prices paid than community hospitals, but the differences were not statistically significant, nor were differences in the study’s utilization outcomes.
Over half the patients had breast cancer, about one-third had colon cancer, and the rest had lung tumors. Patients treated at NCI centers tended to be younger than those treated at community hospitals and more likely to be women, but comorbidity scores were similar between the groups.
NCI centers, compared with community hospitals, were larger with higher surgical volumes and in more populated areas. They also had higher rates of laparoscopic partial colectomies and pneumonectomies.
Data came from the Health Care Cost Institute’s national commercial claims data set, which includes claims from three of the country’s five largest commercial insurers: Aetna, Humana, and UnitedHealthcare.
The work was funded by the Commonwealth of Pennsylvania and the National Cancer Institute. Dr. Takvorian and Dr. Keating didn’t have any disclosures. One of Dr. Takvorian’s coauthors reported grants and/or personal fees from several sources, including Pfizer, UnitedHealthcare, and Blue Cross Blue Shield of North Carolina.
according to a recent report in JAMA Network Open.
“While acceptable to pay higher prices for care that is expected to be of higher quality, we found no differences in short-term postsurgical outcomes,” said authors led by Samuel Takvorian, MD, a medical oncologist at the University of Pennsylvania, Philadelphia.
The team looked at what insurance companies paid for incident breast, colon, and lung cancer surgeries, which together account for most cancer surgeries, among 66,878 patients treated from 2011 to 2014 at almost 3,000 U.S. hospitals.
Three-quarters had surgery at a community hospital, and 8.3% were treated at one of the nation’s 71 NCI centers, which are recognized by the NCI as meeting rigorous standards in cancer care. The remaining patients were treated at non-NCI academic hospitals.
The mean surgery-specific insurer prices paid at NCI centers was $18,526 versus $14,772 at community hospitals, a difference of $3,755 (P < .001) that was driven primarily by higher facility payments at NCI centers, a mean of $17,704 versus $14,120 at community hospitals.
Mean 90-day postdischarge payments were also $5,744 higher at NCI centers, $47,035 versus $41,291 at community hospitals (P = .006).
The team used postsurgical acute care utilization as a marker of quality but found no differences between the two settings. Mean length of stay was 5.1 days and the probability of ED utilization just over 13% in both, and both had a 90-day readmission rate of just over 10%.
Who should be treated at an NCI center?
The data didn’t allow for direct comparison of surgical quality, such as margin status, number of lymph nodes assessed, or postoperative complications, but the postsurgery utilization outcomes “suggest that quality may have been similar,” said Nancy Keating, MD, a health care policy and medicine professor at Harvard Medical School, Boston, in an invited commentary.
The price differences are probably because NCI centers, with their comprehensive offerings, market share, and prestige, can negotiate higher reimbursement rates from insurers, the researchers said.
There is also evidence of better outcomes at NCI centers, particularly for more advanced and complex cases. However, “this study focused on common cancer surgical procedures ... revealing that there is a premium associated with receipt of surgical cancer care at NCI centers.” Further research “is necessary to judge whether and under what circumstances the premium price of NCI centers is justified,” the investigators said.
Dr. Keating noted that “it is likely that some patients benefit from the highly specialized care available at NCI-designated cancer centers ... but it is also likely that many other patients will do equally well regardless of where they receive their care.”
Amid ever-increasing cancer care costs and the need to strategically allocate financial resources, more research is needed to “identify subgroups of patients for whom highly specialized care is particularly necessary to achieve better outcomes. Such data could also be used by payers considering tiered networks and by physician organizations participating in risk contracts for decisions about where to refer patients with cancer for treatment,” she said.
Rectifying a ‘misalignment’
The researchers also said the findings reveal competing incentives, with commercial payers wanting to steer patients away from high-cost hospitals but health systems hoping to maximize surgical volume at lucrative referral centers.
“Value-based or bundled payment reimbursement for surgical episodes, particularly when paired with mandatory reporting on surgical outcomes, could help to rectify this misalignment,” they said.
Out-of-pocket spending wasn’t analyzed in the study, so it’s unknown how the higher prices at NCI centers hit patients in the pocketbook.
Meanwhile, non-NCI academic hospitals also had higher insurer prices paid than community hospitals, but the differences were not statistically significant, nor were differences in the study’s utilization outcomes.
Over half the patients had breast cancer, about one-third had colon cancer, and the rest had lung tumors. Patients treated at NCI centers tended to be younger than those treated at community hospitals and more likely to be women, but comorbidity scores were similar between the groups.
NCI centers, compared with community hospitals, were larger with higher surgical volumes and in more populated areas. They also had higher rates of laparoscopic partial colectomies and pneumonectomies.
Data came from the Health Care Cost Institute’s national commercial claims data set, which includes claims from three of the country’s five largest commercial insurers: Aetna, Humana, and UnitedHealthcare.
The work was funded by the Commonwealth of Pennsylvania and the National Cancer Institute. Dr. Takvorian and Dr. Keating didn’t have any disclosures. One of Dr. Takvorian’s coauthors reported grants and/or personal fees from several sources, including Pfizer, UnitedHealthcare, and Blue Cross Blue Shield of North Carolina.
according to a recent report in JAMA Network Open.
“While acceptable to pay higher prices for care that is expected to be of higher quality, we found no differences in short-term postsurgical outcomes,” said authors led by Samuel Takvorian, MD, a medical oncologist at the University of Pennsylvania, Philadelphia.
The team looked at what insurance companies paid for incident breast, colon, and lung cancer surgeries, which together account for most cancer surgeries, among 66,878 patients treated from 2011 to 2014 at almost 3,000 U.S. hospitals.
Three-quarters had surgery at a community hospital, and 8.3% were treated at one of the nation’s 71 NCI centers, which are recognized by the NCI as meeting rigorous standards in cancer care. The remaining patients were treated at non-NCI academic hospitals.
The mean surgery-specific insurer prices paid at NCI centers was $18,526 versus $14,772 at community hospitals, a difference of $3,755 (P < .001) that was driven primarily by higher facility payments at NCI centers, a mean of $17,704 versus $14,120 at community hospitals.
Mean 90-day postdischarge payments were also $5,744 higher at NCI centers, $47,035 versus $41,291 at community hospitals (P = .006).
The team used postsurgical acute care utilization as a marker of quality but found no differences between the two settings. Mean length of stay was 5.1 days and the probability of ED utilization just over 13% in both, and both had a 90-day readmission rate of just over 10%.
Who should be treated at an NCI center?
The data didn’t allow for direct comparison of surgical quality, such as margin status, number of lymph nodes assessed, or postoperative complications, but the postsurgery utilization outcomes “suggest that quality may have been similar,” said Nancy Keating, MD, a health care policy and medicine professor at Harvard Medical School, Boston, in an invited commentary.
The price differences are probably because NCI centers, with their comprehensive offerings, market share, and prestige, can negotiate higher reimbursement rates from insurers, the researchers said.
There is also evidence of better outcomes at NCI centers, particularly for more advanced and complex cases. However, “this study focused on common cancer surgical procedures ... revealing that there is a premium associated with receipt of surgical cancer care at NCI centers.” Further research “is necessary to judge whether and under what circumstances the premium price of NCI centers is justified,” the investigators said.
Dr. Keating noted that “it is likely that some patients benefit from the highly specialized care available at NCI-designated cancer centers ... but it is also likely that many other patients will do equally well regardless of where they receive their care.”
Amid ever-increasing cancer care costs and the need to strategically allocate financial resources, more research is needed to “identify subgroups of patients for whom highly specialized care is particularly necessary to achieve better outcomes. Such data could also be used by payers considering tiered networks and by physician organizations participating in risk contracts for decisions about where to refer patients with cancer for treatment,” she said.
Rectifying a ‘misalignment’
The researchers also said the findings reveal competing incentives, with commercial payers wanting to steer patients away from high-cost hospitals but health systems hoping to maximize surgical volume at lucrative referral centers.
“Value-based or bundled payment reimbursement for surgical episodes, particularly when paired with mandatory reporting on surgical outcomes, could help to rectify this misalignment,” they said.
Out-of-pocket spending wasn’t analyzed in the study, so it’s unknown how the higher prices at NCI centers hit patients in the pocketbook.
Meanwhile, non-NCI academic hospitals also had higher insurer prices paid than community hospitals, but the differences were not statistically significant, nor were differences in the study’s utilization outcomes.
Over half the patients had breast cancer, about one-third had colon cancer, and the rest had lung tumors. Patients treated at NCI centers tended to be younger than those treated at community hospitals and more likely to be women, but comorbidity scores were similar between the groups.
NCI centers, compared with community hospitals, were larger with higher surgical volumes and in more populated areas. They also had higher rates of laparoscopic partial colectomies and pneumonectomies.
Data came from the Health Care Cost Institute’s national commercial claims data set, which includes claims from three of the country’s five largest commercial insurers: Aetna, Humana, and UnitedHealthcare.
The work was funded by the Commonwealth of Pennsylvania and the National Cancer Institute. Dr. Takvorian and Dr. Keating didn’t have any disclosures. One of Dr. Takvorian’s coauthors reported grants and/or personal fees from several sources, including Pfizer, UnitedHealthcare, and Blue Cross Blue Shield of North Carolina.
FROM JAMA NETWORK OPEN
A case is building for personalized, genome-based radiation dosing
A team of researchers from the Cleveland Clinic, the Moffitt Cancer Center in Tampa, and Case Western Reserve University in Cleveland is zeroing in on a way to personalize radiation therapy for cancer patients based on genomic profile, much as genomics is used to tailor oncologic drug therapy.
It’s called “genomic-adjusted radiation dose” (GARD), a dose tailored to a person’s radiosensitivity as determined by the expression of 10 genes, known as the radiosensitivity index (RSI), combined with a linear quadratic model to yield GARD, a prediction of risk and benefit at various radiation doses for a particular patient.
A recent report in The Lancet Oncology validated GARD in 1,615 patients with seven cancer types from 11 study cohorts. If it holds up in clinical trials set to start later this year, GARD should “allow us to predict the benefit of radiation for an individual patient and adjust their treatment strategy,” wrote the authors of an editorial that accompanied the study. “The efforts need to be applauded worldwide, because radiotherapy is considerably lagging, compared with the enormous progress done in the field of personalized medicine,” Orit Kaidar-Person, MD, a radiation oncologist at Sheba Medical Center in Ramat Gan, Israel, and colleagues wrote.
GARD was associated with time to first recurrence and overall survival for patients receiving radiotherapy and predicted radiotherapy benefit, while physical dose did not. The team found a relative 2% reduction in risk of first recurrence for each unit increase of GARD (P = .0017) and a relative 3% increase in overall survival for each unit increase in GARD (P = .0007), among those who got radiotherapy. Values of GARD run from 0 to over 100, with higher scores meaning more radiation benefit.
The radiosensitivity index, which was derived from genomic studies of cancer cell lines exposed to radiation, was previously validated by the team and other groups across several tumor types.
Currently, radiation dosing is generally uniform for a given disease site and stage, based on the assumption that a given dose of radiation results in the same clinical effect across patients. In fact, the biological effect of a given dose varies widely between individual patients. “Patients we treat uniformly do not have a uniform response” which is why a more personalized approach would help, said lead investigator and Cleveland Clinic radiation oncologist Jacob Scott, MD, DPhil.
One patient with a given tumor might benefit from 2 extra fractions, while the next might need an extra 15 for the same benefit. “You need to know about [a patient’s] tumor genomics to know how hard you have to work,” he said.
Dr. Scott and colleagues are working with a genomics company to commercialize the approach. The vision for now is that physicians would ship in biopsy samples to be analyzed; RSI and GARD would be calculated, and then a decision support report would be sent back to the treatment team outlining the risks and benefits of various doses for the patient.
Dr. Scott, who holds proprietary rights on the approach, is bullish. When asked if he anticipates GARD dosing to be standard of care in 10 years, he said that “I can’t imagine another world. Everything else in cancer is personalized. Why aren’t we? It just makes sense. I know there’s a better way” to prescribe radiation, “and I’m excited for the future when I can use it.”
When asked for comment, Brian Marples, PhD, a radiation oncology professor at the University of Rochester (N.Y.), said the data so far for GARD “seem very solid. I’m very excited by the concept.”
It’s been “the holy grail” of radiation researchers to find a biologic marker that predicts what dosages patients need and what can be given safely. “This strategy is a good way of doing that. Other groups are proposing similar strategies, but I think this group is ahead. I can see [GARD] being readily applied to the clinic because patients are [already] getting their tumors genomically characterized as part of care,” Dr. Marples said.
But many questions remain. For instance, the editorial writers questioned how GARD is “affected by tumor heterogeneity, response to systemic therapy, and changes in the tumor microenvironment.” Also, the approach is based on conventional 2 Gy fractions, but other fractionation regimens are becoming more common.
For Dr. Marples, the big caveat is that most cancer patients are treated with both radiation and chemotherapy. He said he would like to see GARD validated in patients who receive both.
They seven tumor types in the study included breast cancer, head and neck cancer, non–small cell lung cancer, pancreatic cancer, endometrial cancer, melanoma, and glioma. The majority of the subjects were treated with radiation, and each had the genomic data needed to calculate GARD.
Dr. Scott, senior author and Moffitt Center radiation oncologist Javier Torres-Roca, MD, and a third author hold intellectual property rights on RSI, GARD, and prescription dose base on RSI, plus equity in Cvergenx, a company that seeks to commercialize the approach. Dr. Torres-Roca and another author are cofounders. The editorial writers and Dr. Marples did not have any relevant disclosures.
A team of researchers from the Cleveland Clinic, the Moffitt Cancer Center in Tampa, and Case Western Reserve University in Cleveland is zeroing in on a way to personalize radiation therapy for cancer patients based on genomic profile, much as genomics is used to tailor oncologic drug therapy.
It’s called “genomic-adjusted radiation dose” (GARD), a dose tailored to a person’s radiosensitivity as determined by the expression of 10 genes, known as the radiosensitivity index (RSI), combined with a linear quadratic model to yield GARD, a prediction of risk and benefit at various radiation doses for a particular patient.
A recent report in The Lancet Oncology validated GARD in 1,615 patients with seven cancer types from 11 study cohorts. If it holds up in clinical trials set to start later this year, GARD should “allow us to predict the benefit of radiation for an individual patient and adjust their treatment strategy,” wrote the authors of an editorial that accompanied the study. “The efforts need to be applauded worldwide, because radiotherapy is considerably lagging, compared with the enormous progress done in the field of personalized medicine,” Orit Kaidar-Person, MD, a radiation oncologist at Sheba Medical Center in Ramat Gan, Israel, and colleagues wrote.
GARD was associated with time to first recurrence and overall survival for patients receiving radiotherapy and predicted radiotherapy benefit, while physical dose did not. The team found a relative 2% reduction in risk of first recurrence for each unit increase of GARD (P = .0017) and a relative 3% increase in overall survival for each unit increase in GARD (P = .0007), among those who got radiotherapy. Values of GARD run from 0 to over 100, with higher scores meaning more radiation benefit.
The radiosensitivity index, which was derived from genomic studies of cancer cell lines exposed to radiation, was previously validated by the team and other groups across several tumor types.
Currently, radiation dosing is generally uniform for a given disease site and stage, based on the assumption that a given dose of radiation results in the same clinical effect across patients. In fact, the biological effect of a given dose varies widely between individual patients. “Patients we treat uniformly do not have a uniform response” which is why a more personalized approach would help, said lead investigator and Cleveland Clinic radiation oncologist Jacob Scott, MD, DPhil.
One patient with a given tumor might benefit from 2 extra fractions, while the next might need an extra 15 for the same benefit. “You need to know about [a patient’s] tumor genomics to know how hard you have to work,” he said.
Dr. Scott and colleagues are working with a genomics company to commercialize the approach. The vision for now is that physicians would ship in biopsy samples to be analyzed; RSI and GARD would be calculated, and then a decision support report would be sent back to the treatment team outlining the risks and benefits of various doses for the patient.
Dr. Scott, who holds proprietary rights on the approach, is bullish. When asked if he anticipates GARD dosing to be standard of care in 10 years, he said that “I can’t imagine another world. Everything else in cancer is personalized. Why aren’t we? It just makes sense. I know there’s a better way” to prescribe radiation, “and I’m excited for the future when I can use it.”
When asked for comment, Brian Marples, PhD, a radiation oncology professor at the University of Rochester (N.Y.), said the data so far for GARD “seem very solid. I’m very excited by the concept.”
It’s been “the holy grail” of radiation researchers to find a biologic marker that predicts what dosages patients need and what can be given safely. “This strategy is a good way of doing that. Other groups are proposing similar strategies, but I think this group is ahead. I can see [GARD] being readily applied to the clinic because patients are [already] getting their tumors genomically characterized as part of care,” Dr. Marples said.
But many questions remain. For instance, the editorial writers questioned how GARD is “affected by tumor heterogeneity, response to systemic therapy, and changes in the tumor microenvironment.” Also, the approach is based on conventional 2 Gy fractions, but other fractionation regimens are becoming more common.
For Dr. Marples, the big caveat is that most cancer patients are treated with both radiation and chemotherapy. He said he would like to see GARD validated in patients who receive both.
They seven tumor types in the study included breast cancer, head and neck cancer, non–small cell lung cancer, pancreatic cancer, endometrial cancer, melanoma, and glioma. The majority of the subjects were treated with radiation, and each had the genomic data needed to calculate GARD.
Dr. Scott, senior author and Moffitt Center radiation oncologist Javier Torres-Roca, MD, and a third author hold intellectual property rights on RSI, GARD, and prescription dose base on RSI, plus equity in Cvergenx, a company that seeks to commercialize the approach. Dr. Torres-Roca and another author are cofounders. The editorial writers and Dr. Marples did not have any relevant disclosures.
A team of researchers from the Cleveland Clinic, the Moffitt Cancer Center in Tampa, and Case Western Reserve University in Cleveland is zeroing in on a way to personalize radiation therapy for cancer patients based on genomic profile, much as genomics is used to tailor oncologic drug therapy.
It’s called “genomic-adjusted radiation dose” (GARD), a dose tailored to a person’s radiosensitivity as determined by the expression of 10 genes, known as the radiosensitivity index (RSI), combined with a linear quadratic model to yield GARD, a prediction of risk and benefit at various radiation doses for a particular patient.
A recent report in The Lancet Oncology validated GARD in 1,615 patients with seven cancer types from 11 study cohorts. If it holds up in clinical trials set to start later this year, GARD should “allow us to predict the benefit of radiation for an individual patient and adjust their treatment strategy,” wrote the authors of an editorial that accompanied the study. “The efforts need to be applauded worldwide, because radiotherapy is considerably lagging, compared with the enormous progress done in the field of personalized medicine,” Orit Kaidar-Person, MD, a radiation oncologist at Sheba Medical Center in Ramat Gan, Israel, and colleagues wrote.
GARD was associated with time to first recurrence and overall survival for patients receiving radiotherapy and predicted radiotherapy benefit, while physical dose did not. The team found a relative 2% reduction in risk of first recurrence for each unit increase of GARD (P = .0017) and a relative 3% increase in overall survival for each unit increase in GARD (P = .0007), among those who got radiotherapy. Values of GARD run from 0 to over 100, with higher scores meaning more radiation benefit.
The radiosensitivity index, which was derived from genomic studies of cancer cell lines exposed to radiation, was previously validated by the team and other groups across several tumor types.
Currently, radiation dosing is generally uniform for a given disease site and stage, based on the assumption that a given dose of radiation results in the same clinical effect across patients. In fact, the biological effect of a given dose varies widely between individual patients. “Patients we treat uniformly do not have a uniform response” which is why a more personalized approach would help, said lead investigator and Cleveland Clinic radiation oncologist Jacob Scott, MD, DPhil.
One patient with a given tumor might benefit from 2 extra fractions, while the next might need an extra 15 for the same benefit. “You need to know about [a patient’s] tumor genomics to know how hard you have to work,” he said.
Dr. Scott and colleagues are working with a genomics company to commercialize the approach. The vision for now is that physicians would ship in biopsy samples to be analyzed; RSI and GARD would be calculated, and then a decision support report would be sent back to the treatment team outlining the risks and benefits of various doses for the patient.
Dr. Scott, who holds proprietary rights on the approach, is bullish. When asked if he anticipates GARD dosing to be standard of care in 10 years, he said that “I can’t imagine another world. Everything else in cancer is personalized. Why aren’t we? It just makes sense. I know there’s a better way” to prescribe radiation, “and I’m excited for the future when I can use it.”
When asked for comment, Brian Marples, PhD, a radiation oncology professor at the University of Rochester (N.Y.), said the data so far for GARD “seem very solid. I’m very excited by the concept.”
It’s been “the holy grail” of radiation researchers to find a biologic marker that predicts what dosages patients need and what can be given safely. “This strategy is a good way of doing that. Other groups are proposing similar strategies, but I think this group is ahead. I can see [GARD] being readily applied to the clinic because patients are [already] getting their tumors genomically characterized as part of care,” Dr. Marples said.
But many questions remain. For instance, the editorial writers questioned how GARD is “affected by tumor heterogeneity, response to systemic therapy, and changes in the tumor microenvironment.” Also, the approach is based on conventional 2 Gy fractions, but other fractionation regimens are becoming more common.
For Dr. Marples, the big caveat is that most cancer patients are treated with both radiation and chemotherapy. He said he would like to see GARD validated in patients who receive both.
They seven tumor types in the study included breast cancer, head and neck cancer, non–small cell lung cancer, pancreatic cancer, endometrial cancer, melanoma, and glioma. The majority of the subjects were treated with radiation, and each had the genomic data needed to calculate GARD.
Dr. Scott, senior author and Moffitt Center radiation oncologist Javier Torres-Roca, MD, and a third author hold intellectual property rights on RSI, GARD, and prescription dose base on RSI, plus equity in Cvergenx, a company that seeks to commercialize the approach. Dr. Torres-Roca and another author are cofounders. The editorial writers and Dr. Marples did not have any relevant disclosures.
FROM LANCET ONCOLOGY
Dostarlimab indication broadened to all dMMR solid tumors
The agency approved the drug in April for dMMR recurrent or advanced endometrial cancer that has progressed during or following treatment with a platinum-containing regimen. The labeling notes that dMMR status for both indications must be determined through an FDA-approved test.
The accelerated approval “may be contingent upon verification and description of clinical benefit in a confirmatory” trial, the labeling says.
The new indication was based results from 209 patients in the GARNET trial. In that trial, the objective response rate was 41.6% across dMMR endometrial and other solid tumors. The complete response rate was 9.1%.
The median duration of response was 34.7 months. For 95% of patients who responded to treatment, the duration of response was 6 months or longer, according to a press release from the maker, GlaxoSmithKline.
In mismatch repair deficiency, tumors contain abnormalities that affect the proper repair of DNA. Prevalence in the United States is estimated to be 14%. The deficiency is particularly common in endometrial, colorectal, and other gastrointestinal cancers, the company said.
The drug was administered in GARNET as a 500-mg intravenous infusion every 3 weeks in four doses, followed by 1,000 mg once every 6 weeks until disease progression or unacceptable toxicity.
Common adverse events included fatigue/asthenia (42%), anemia (30%), diarrhea (25%), and nausea (22%). The most common grade 3 or 4 adverse reactions included anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury.
As with other PD-1/PD-L1 blockers, there’s also a possibility of severe and fatal immune-mediated adverse reactions in any organ system either during or after treatment, including immune-mediated pneumonitis, colitis, and hepatitis.
GlaxoSmithKline said it’s studying dostarlimab in earlier lines of treatment for endometrial cancer and in combination with other agents for other advanced/metastatic cancers.
A version of this article first appeared on Medscape.com.
The agency approved the drug in April for dMMR recurrent or advanced endometrial cancer that has progressed during or following treatment with a platinum-containing regimen. The labeling notes that dMMR status for both indications must be determined through an FDA-approved test.
The accelerated approval “may be contingent upon verification and description of clinical benefit in a confirmatory” trial, the labeling says.
The new indication was based results from 209 patients in the GARNET trial. In that trial, the objective response rate was 41.6% across dMMR endometrial and other solid tumors. The complete response rate was 9.1%.
The median duration of response was 34.7 months. For 95% of patients who responded to treatment, the duration of response was 6 months or longer, according to a press release from the maker, GlaxoSmithKline.
In mismatch repair deficiency, tumors contain abnormalities that affect the proper repair of DNA. Prevalence in the United States is estimated to be 14%. The deficiency is particularly common in endometrial, colorectal, and other gastrointestinal cancers, the company said.
The drug was administered in GARNET as a 500-mg intravenous infusion every 3 weeks in four doses, followed by 1,000 mg once every 6 weeks until disease progression or unacceptable toxicity.
Common adverse events included fatigue/asthenia (42%), anemia (30%), diarrhea (25%), and nausea (22%). The most common grade 3 or 4 adverse reactions included anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury.
As with other PD-1/PD-L1 blockers, there’s also a possibility of severe and fatal immune-mediated adverse reactions in any organ system either during or after treatment, including immune-mediated pneumonitis, colitis, and hepatitis.
GlaxoSmithKline said it’s studying dostarlimab in earlier lines of treatment for endometrial cancer and in combination with other agents for other advanced/metastatic cancers.
A version of this article first appeared on Medscape.com.
The agency approved the drug in April for dMMR recurrent or advanced endometrial cancer that has progressed during or following treatment with a platinum-containing regimen. The labeling notes that dMMR status for both indications must be determined through an FDA-approved test.
The accelerated approval “may be contingent upon verification and description of clinical benefit in a confirmatory” trial, the labeling says.
The new indication was based results from 209 patients in the GARNET trial. In that trial, the objective response rate was 41.6% across dMMR endometrial and other solid tumors. The complete response rate was 9.1%.
The median duration of response was 34.7 months. For 95% of patients who responded to treatment, the duration of response was 6 months or longer, according to a press release from the maker, GlaxoSmithKline.
In mismatch repair deficiency, tumors contain abnormalities that affect the proper repair of DNA. Prevalence in the United States is estimated to be 14%. The deficiency is particularly common in endometrial, colorectal, and other gastrointestinal cancers, the company said.
The drug was administered in GARNET as a 500-mg intravenous infusion every 3 weeks in four doses, followed by 1,000 mg once every 6 weeks until disease progression or unacceptable toxicity.
Common adverse events included fatigue/asthenia (42%), anemia (30%), diarrhea (25%), and nausea (22%). The most common grade 3 or 4 adverse reactions included anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury.
As with other PD-1/PD-L1 blockers, there’s also a possibility of severe and fatal immune-mediated adverse reactions in any organ system either during or after treatment, including immune-mediated pneumonitis, colitis, and hepatitis.
GlaxoSmithKline said it’s studying dostarlimab in earlier lines of treatment for endometrial cancer and in combination with other agents for other advanced/metastatic cancers.
A version of this article first appeared on Medscape.com.