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Chemotherapy with a platinum-based doublet was associated with a highly significant 36% reduction in mortality, compared with monotherapy, among elderly patients with non–small cell lung cancer in a study published online Aug. 9 by the Lancet.
The combination of carboplatin and paclitaxel was associated with more toxicity than was single-drug vinorelbine or gemcitabine regimens in the phase III trial, but the investigators contended that this was outweighed by the survival benefit.
Median overall survival for patients receiving carboplatin plus paclitaxel was 10.3 months, compared with 6.2 months in those randomized to monotherapy (hazard ratio, 0.64; P less than .0001).
Although several guidelines currently recommend monotherapy for elderly patients, the current finding is "of such magnitude that we believe the treatment paradigm for elderly patients with advanced NSCLC should be reconsidered," wrote Dr. Elisabeth Quoix of the Hôpitaux Universitaires de Strasbourg (France) and colleagues (Lancet 2011 Aug. 9 [doi:10.1016/S0140-6736(11)60780-0]).
The investigators from the IFCT (Intergroupe Francophone de Cancérologie Thoracique) looked at 451 patients aged 70-89 years (median age, 77 years) with unresectable stage IV NSCLC or stage III disease that was "unsuitable" for radical radiation therapy. Patients were followed for a median of 30.3 months. To be included in the study, patients’ scores on the World Health Organization’s performance status scale had to be 2 or lower (indicating severe disease), and patients had to have a life expectancy of at least 12 weeks.
The 225 patients who were randomized to the doublet chemotherapy group received intravenous carboplatin (AUC [area under the curve] = 6) on day 1, plus 90 mg/m² of paclitaxel on days 1, 8, and 15 of 28-day cycles.
The 226-patient monotherapy cohort received 25 mg/m² vinorelbine (62 patients) on days 1 and 8 – or 1,150 mg/m² gemcitabine (164 patients) on days 1 and 8 – of 21-day cycles, with the choice of either vinorelbine or gemcitabine being made by the institution conducting the therapy.
In the doublet group, cycles were repeated every 4 weeks, such that patients received 3 weeks of treatment plus 1 week without, for doublet chemotherapy. For monotherapy, the cycle lasted 3 weeks (2 weeks of treatment plus 1 week without), with a maximum of four cycles for doublet therapy and five cycles for monotherapy.
Survival Rates for Chemotherapy Study Patients
By 1 year, the survival rate was 25.4% in the monotherapy group vs. 44.5% in the doublet therapy group (HR, 0.64; P less than .0001). The trend persisted at 2 years, with the probability of survival being 11.7% in monotherapy recipients and 22.4% in those receiving doublet therapy, wrote the authors.
Median progression-free survival also was significantly longer with the doublet (6 months vs. 2.8 months; P less than .0001).
In 2009, an independent data-monitoring committee recommended stopping recruitment based on the second interim analysis.
"Grade 3-4 neutropenia, febrile neutropenia, thrombopenia, and anemia were significantly more frequent among patients in the doublet chemotherapy group than among those in the monotherapy group, as was grade 3-4 sensory neuropathy," wrote the authors. The protocol did not allow growth factor support in the first cycle, but it was authorized as secondary prophylaxis in patients who developed grade 3 or 4 neutropenia.
In all, 10 deaths in the doublet therapy group (4.4%) and 3 in the monotherapy group (1.3%) were related to treatment: Culprit diagnoses included sepsis, respiratory distress, and diarrhea related to renal insufficiency. But the percentage of deaths in the first 3 months after the start of therapy was "markedly lower" in patients who received carboplatin plus paclitaxel.
Although quality of life scores at week 18 were similar between groups, the authors pointed out that "role functioning and fatigue were worse in the doublet chemotherapy group than in the monotherapy group" (P = .026 and .039, respectively). Full quality of life data will be published separately, they said.
The 2009 American Society of Clinical Oncology guidelines (J. Clin. Oncol. 2009;27:6251-66) recommend that age "not be used as a criterion in the decision-making process about whether to treat a patient" and call for further research devoted to elderly patients, according to Dr. Quoix and colleagues. "Conversely," they noted, "the European Organisation for Research and Treatment of Cancer Elderly Task Force and Lung Cancer Group and International Society of Geriatric Oncology highlighted in 2010 that monotherapy should be given to elderly patients with advanced NSCLC."
"We believe that monthly carboplatin and weekly paclitaxel is a feasible option for first-line therapy of advanced NSCLC in patients older than 70 years with performance status scores of 0-2," the authors wrote.
The study was funded by the IFCT and the French National Cancer Institute, with support by grants from Bristol-Myers Squibb, Roche, and Pierre Fabre. Several authors, including Dr. Quoix, disclosed financial relationships with the makers of chemotherapy drugs, including carboplatin (Bristol-Myers Squibb, Roche, and Lilly). Dr. Reckamp disclosed consulting for Amgen, Genentech, and Tragara Pharmaceuticals, as well as serving on speakers bureaus for Lilly Oncology and Genentech.
In an editorial accompanying the study, Dr. Karen L. Reckamp wrote that although older patients dominate the lung cancer population, they nevertheless continue to be underrepresented in clinical trials. Accounting for 47% of the U.S. adults with cancer, patients aged 70 years or older constitute just 13% of patients who are enrolled in clinical trials, according to the Southern Italy Cooperative Oncology Group (SICOG).
Nevertheless, there are some studies that provide guidance, she wrote.
A study by the SICOG compared vinorelbine alone with vinorelbine plus gemcitabine in patients aged 70 years and older (J. Clin. Oncol. 2000;18:2529-36). "Combination chemotherapy resulted in a significantly lower risk of death," she wrote. "Adverse events were greater in the combination group, but patients had a delay" in quality of life deterioration.
A second investigation, MILES (Multicenter Italian Lung Cancer in the Elderly Study), compared vinorelbine or gemcitabine alone or in combination. "Combination therapy did not improve overall survival and was more toxic than was either single-agent regimen," wrote Dr. Reckamp.
A third study from Japan was stopped because of futility when the interim analysis showed inferior survival with increased toxic effects in patients who were treated with weekly cisplatin and docetaxel vs. docetaxel every 3 weeks (J. Clin. Oncol. 2011;29:abstract 7509).
"The appropriate assessment to predict efficacy and toxic effects of therapy has not yet been identified," said Dr. Reckamp. As previous trials assessed multiple regimens with fractionated doses and non–platinum-based doublets, "the optimum chemotherapy regimen remains unknown, she added, concluding that "additional studies are needed that enroll adequate numbers of older adults, and include a comprehensive geriatric assessment to provide the knowledge required to properly assess the risk-benefit ratio in treatment decisions, so that a personalized approach can be taken."
Dr. Reckamp is at the City of Hope Comprehensive Cancer Center in Duarte, Calif. She disclosed consulting for Amgen, Genentech, and Tragara Pharmaceuticals, as well as serving on speakers bureaus for Lilly Oncology and Genentech. These remarks were adapted from an editorial that accompanied the study (Lancet 2011 Aug. 9 [doi:10.1016/S0140-6736(11)61259-2]).
In an editorial accompanying the study, Dr. Karen L. Reckamp wrote that although older patients dominate the lung cancer population, they nevertheless continue to be underrepresented in clinical trials. Accounting for 47% of the U.S. adults with cancer, patients aged 70 years or older constitute just 13% of patients who are enrolled in clinical trials, according to the Southern Italy Cooperative Oncology Group (SICOG).
Nevertheless, there are some studies that provide guidance, she wrote.
A study by the SICOG compared vinorelbine alone with vinorelbine plus gemcitabine in patients aged 70 years and older (J. Clin. Oncol. 2000;18:2529-36). "Combination chemotherapy resulted in a significantly lower risk of death," she wrote. "Adverse events were greater in the combination group, but patients had a delay" in quality of life deterioration.
A second investigation, MILES (Multicenter Italian Lung Cancer in the Elderly Study), compared vinorelbine or gemcitabine alone or in combination. "Combination therapy did not improve overall survival and was more toxic than was either single-agent regimen," wrote Dr. Reckamp.
A third study from Japan was stopped because of futility when the interim analysis showed inferior survival with increased toxic effects in patients who were treated with weekly cisplatin and docetaxel vs. docetaxel every 3 weeks (J. Clin. Oncol. 2011;29:abstract 7509).
"The appropriate assessment to predict efficacy and toxic effects of therapy has not yet been identified," said Dr. Reckamp. As previous trials assessed multiple regimens with fractionated doses and non–platinum-based doublets, "the optimum chemotherapy regimen remains unknown, she added, concluding that "additional studies are needed that enroll adequate numbers of older adults, and include a comprehensive geriatric assessment to provide the knowledge required to properly assess the risk-benefit ratio in treatment decisions, so that a personalized approach can be taken."
Dr. Reckamp is at the City of Hope Comprehensive Cancer Center in Duarte, Calif. She disclosed consulting for Amgen, Genentech, and Tragara Pharmaceuticals, as well as serving on speakers bureaus for Lilly Oncology and Genentech. These remarks were adapted from an editorial that accompanied the study (Lancet 2011 Aug. 9 [doi:10.1016/S0140-6736(11)61259-2]).
In an editorial accompanying the study, Dr. Karen L. Reckamp wrote that although older patients dominate the lung cancer population, they nevertheless continue to be underrepresented in clinical trials. Accounting for 47% of the U.S. adults with cancer, patients aged 70 years or older constitute just 13% of patients who are enrolled in clinical trials, according to the Southern Italy Cooperative Oncology Group (SICOG).
Nevertheless, there are some studies that provide guidance, she wrote.
A study by the SICOG compared vinorelbine alone with vinorelbine plus gemcitabine in patients aged 70 years and older (J. Clin. Oncol. 2000;18:2529-36). "Combination chemotherapy resulted in a significantly lower risk of death," she wrote. "Adverse events were greater in the combination group, but patients had a delay" in quality of life deterioration.
A second investigation, MILES (Multicenter Italian Lung Cancer in the Elderly Study), compared vinorelbine or gemcitabine alone or in combination. "Combination therapy did not improve overall survival and was more toxic than was either single-agent regimen," wrote Dr. Reckamp.
A third study from Japan was stopped because of futility when the interim analysis showed inferior survival with increased toxic effects in patients who were treated with weekly cisplatin and docetaxel vs. docetaxel every 3 weeks (J. Clin. Oncol. 2011;29:abstract 7509).
"The appropriate assessment to predict efficacy and toxic effects of therapy has not yet been identified," said Dr. Reckamp. As previous trials assessed multiple regimens with fractionated doses and non–platinum-based doublets, "the optimum chemotherapy regimen remains unknown, she added, concluding that "additional studies are needed that enroll adequate numbers of older adults, and include a comprehensive geriatric assessment to provide the knowledge required to properly assess the risk-benefit ratio in treatment decisions, so that a personalized approach can be taken."
Dr. Reckamp is at the City of Hope Comprehensive Cancer Center in Duarte, Calif. She disclosed consulting for Amgen, Genentech, and Tragara Pharmaceuticals, as well as serving on speakers bureaus for Lilly Oncology and Genentech. These remarks were adapted from an editorial that accompanied the study (Lancet 2011 Aug. 9 [doi:10.1016/S0140-6736(11)61259-2]).
Chemotherapy with a platinum-based doublet was associated with a highly significant 36% reduction in mortality, compared with monotherapy, among elderly patients with non–small cell lung cancer in a study published online Aug. 9 by the Lancet.
The combination of carboplatin and paclitaxel was associated with more toxicity than was single-drug vinorelbine or gemcitabine regimens in the phase III trial, but the investigators contended that this was outweighed by the survival benefit.
Median overall survival for patients receiving carboplatin plus paclitaxel was 10.3 months, compared with 6.2 months in those randomized to monotherapy (hazard ratio, 0.64; P less than .0001).
Although several guidelines currently recommend monotherapy for elderly patients, the current finding is "of such magnitude that we believe the treatment paradigm for elderly patients with advanced NSCLC should be reconsidered," wrote Dr. Elisabeth Quoix of the Hôpitaux Universitaires de Strasbourg (France) and colleagues (Lancet 2011 Aug. 9 [doi:10.1016/S0140-6736(11)60780-0]).
The investigators from the IFCT (Intergroupe Francophone de Cancérologie Thoracique) looked at 451 patients aged 70-89 years (median age, 77 years) with unresectable stage IV NSCLC or stage III disease that was "unsuitable" for radical radiation therapy. Patients were followed for a median of 30.3 months. To be included in the study, patients’ scores on the World Health Organization’s performance status scale had to be 2 or lower (indicating severe disease), and patients had to have a life expectancy of at least 12 weeks.
The 225 patients who were randomized to the doublet chemotherapy group received intravenous carboplatin (AUC [area under the curve] = 6) on day 1, plus 90 mg/m² of paclitaxel on days 1, 8, and 15 of 28-day cycles.
The 226-patient monotherapy cohort received 25 mg/m² vinorelbine (62 patients) on days 1 and 8 – or 1,150 mg/m² gemcitabine (164 patients) on days 1 and 8 – of 21-day cycles, with the choice of either vinorelbine or gemcitabine being made by the institution conducting the therapy.
In the doublet group, cycles were repeated every 4 weeks, such that patients received 3 weeks of treatment plus 1 week without, for doublet chemotherapy. For monotherapy, the cycle lasted 3 weeks (2 weeks of treatment plus 1 week without), with a maximum of four cycles for doublet therapy and five cycles for monotherapy.
Survival Rates for Chemotherapy Study Patients
By 1 year, the survival rate was 25.4% in the monotherapy group vs. 44.5% in the doublet therapy group (HR, 0.64; P less than .0001). The trend persisted at 2 years, with the probability of survival being 11.7% in monotherapy recipients and 22.4% in those receiving doublet therapy, wrote the authors.
Median progression-free survival also was significantly longer with the doublet (6 months vs. 2.8 months; P less than .0001).
In 2009, an independent data-monitoring committee recommended stopping recruitment based on the second interim analysis.
"Grade 3-4 neutropenia, febrile neutropenia, thrombopenia, and anemia were significantly more frequent among patients in the doublet chemotherapy group than among those in the monotherapy group, as was grade 3-4 sensory neuropathy," wrote the authors. The protocol did not allow growth factor support in the first cycle, but it was authorized as secondary prophylaxis in patients who developed grade 3 or 4 neutropenia.
In all, 10 deaths in the doublet therapy group (4.4%) and 3 in the monotherapy group (1.3%) were related to treatment: Culprit diagnoses included sepsis, respiratory distress, and diarrhea related to renal insufficiency. But the percentage of deaths in the first 3 months after the start of therapy was "markedly lower" in patients who received carboplatin plus paclitaxel.
Although quality of life scores at week 18 were similar between groups, the authors pointed out that "role functioning and fatigue were worse in the doublet chemotherapy group than in the monotherapy group" (P = .026 and .039, respectively). Full quality of life data will be published separately, they said.
The 2009 American Society of Clinical Oncology guidelines (J. Clin. Oncol. 2009;27:6251-66) recommend that age "not be used as a criterion in the decision-making process about whether to treat a patient" and call for further research devoted to elderly patients, according to Dr. Quoix and colleagues. "Conversely," they noted, "the European Organisation for Research and Treatment of Cancer Elderly Task Force and Lung Cancer Group and International Society of Geriatric Oncology highlighted in 2010 that monotherapy should be given to elderly patients with advanced NSCLC."
"We believe that monthly carboplatin and weekly paclitaxel is a feasible option for first-line therapy of advanced NSCLC in patients older than 70 years with performance status scores of 0-2," the authors wrote.
The study was funded by the IFCT and the French National Cancer Institute, with support by grants from Bristol-Myers Squibb, Roche, and Pierre Fabre. Several authors, including Dr. Quoix, disclosed financial relationships with the makers of chemotherapy drugs, including carboplatin (Bristol-Myers Squibb, Roche, and Lilly). Dr. Reckamp disclosed consulting for Amgen, Genentech, and Tragara Pharmaceuticals, as well as serving on speakers bureaus for Lilly Oncology and Genentech.
Chemotherapy with a platinum-based doublet was associated with a highly significant 36% reduction in mortality, compared with monotherapy, among elderly patients with non–small cell lung cancer in a study published online Aug. 9 by the Lancet.
The combination of carboplatin and paclitaxel was associated with more toxicity than was single-drug vinorelbine or gemcitabine regimens in the phase III trial, but the investigators contended that this was outweighed by the survival benefit.
Median overall survival for patients receiving carboplatin plus paclitaxel was 10.3 months, compared with 6.2 months in those randomized to monotherapy (hazard ratio, 0.64; P less than .0001).
Although several guidelines currently recommend monotherapy for elderly patients, the current finding is "of such magnitude that we believe the treatment paradigm for elderly patients with advanced NSCLC should be reconsidered," wrote Dr. Elisabeth Quoix of the Hôpitaux Universitaires de Strasbourg (France) and colleagues (Lancet 2011 Aug. 9 [doi:10.1016/S0140-6736(11)60780-0]).
The investigators from the IFCT (Intergroupe Francophone de Cancérologie Thoracique) looked at 451 patients aged 70-89 years (median age, 77 years) with unresectable stage IV NSCLC or stage III disease that was "unsuitable" for radical radiation therapy. Patients were followed for a median of 30.3 months. To be included in the study, patients’ scores on the World Health Organization’s performance status scale had to be 2 or lower (indicating severe disease), and patients had to have a life expectancy of at least 12 weeks.
The 225 patients who were randomized to the doublet chemotherapy group received intravenous carboplatin (AUC [area under the curve] = 6) on day 1, plus 90 mg/m² of paclitaxel on days 1, 8, and 15 of 28-day cycles.
The 226-patient monotherapy cohort received 25 mg/m² vinorelbine (62 patients) on days 1 and 8 – or 1,150 mg/m² gemcitabine (164 patients) on days 1 and 8 – of 21-day cycles, with the choice of either vinorelbine or gemcitabine being made by the institution conducting the therapy.
In the doublet group, cycles were repeated every 4 weeks, such that patients received 3 weeks of treatment plus 1 week without, for doublet chemotherapy. For monotherapy, the cycle lasted 3 weeks (2 weeks of treatment plus 1 week without), with a maximum of four cycles for doublet therapy and five cycles for monotherapy.
Survival Rates for Chemotherapy Study Patients
By 1 year, the survival rate was 25.4% in the monotherapy group vs. 44.5% in the doublet therapy group (HR, 0.64; P less than .0001). The trend persisted at 2 years, with the probability of survival being 11.7% in monotherapy recipients and 22.4% in those receiving doublet therapy, wrote the authors.
Median progression-free survival also was significantly longer with the doublet (6 months vs. 2.8 months; P less than .0001).
In 2009, an independent data-monitoring committee recommended stopping recruitment based on the second interim analysis.
"Grade 3-4 neutropenia, febrile neutropenia, thrombopenia, and anemia were significantly more frequent among patients in the doublet chemotherapy group than among those in the monotherapy group, as was grade 3-4 sensory neuropathy," wrote the authors. The protocol did not allow growth factor support in the first cycle, but it was authorized as secondary prophylaxis in patients who developed grade 3 or 4 neutropenia.
In all, 10 deaths in the doublet therapy group (4.4%) and 3 in the monotherapy group (1.3%) were related to treatment: Culprit diagnoses included sepsis, respiratory distress, and diarrhea related to renal insufficiency. But the percentage of deaths in the first 3 months after the start of therapy was "markedly lower" in patients who received carboplatin plus paclitaxel.
Although quality of life scores at week 18 were similar between groups, the authors pointed out that "role functioning and fatigue were worse in the doublet chemotherapy group than in the monotherapy group" (P = .026 and .039, respectively). Full quality of life data will be published separately, they said.
The 2009 American Society of Clinical Oncology guidelines (J. Clin. Oncol. 2009;27:6251-66) recommend that age "not be used as a criterion in the decision-making process about whether to treat a patient" and call for further research devoted to elderly patients, according to Dr. Quoix and colleagues. "Conversely," they noted, "the European Organisation for Research and Treatment of Cancer Elderly Task Force and Lung Cancer Group and International Society of Geriatric Oncology highlighted in 2010 that monotherapy should be given to elderly patients with advanced NSCLC."
"We believe that monthly carboplatin and weekly paclitaxel is a feasible option for first-line therapy of advanced NSCLC in patients older than 70 years with performance status scores of 0-2," the authors wrote.
The study was funded by the IFCT and the French National Cancer Institute, with support by grants from Bristol-Myers Squibb, Roche, and Pierre Fabre. Several authors, including Dr. Quoix, disclosed financial relationships with the makers of chemotherapy drugs, including carboplatin (Bristol-Myers Squibb, Roche, and Lilly). Dr. Reckamp disclosed consulting for Amgen, Genentech, and Tragara Pharmaceuticals, as well as serving on speakers bureaus for Lilly Oncology and Genentech.
FROM THE LANCET
Major Finding: By 1 year, median overall survival was 25.4% with monotherapy, vs. 44.5% with a carboplatin and paclitaxel doublet.
Data Source: A multicenter, open-label, phase III, randomized trial in NSCLC patients aged 70-89 years.
Disclosures: The study was funded by the IFCT and the French National Cancer Institute, with support by grants from Bristol-Myers Squibb, Roche, and Pierre Fabre. Several authors, including Dr. Quoix, disclosed financial relationships with the makers of chemotherapy drugs, including carboplatin (Bristol-Myers Squibb, Roche, and Lilly).