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Biomarker-driven targeted therapy was found feasible for heavily pretreated, metastatic non–small-cell lung cancer in a phase II trial reported online Aug. 1 in the Journal of Clinical Oncology.
The open-label multicenter umbrella study under the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, called the BATTLE-2, involved 200 patients with advanced NSCLC refractory to platinum-based chemotherapy and multiple other treatments. All patients underwent tumor tissue biopsies for biomarker and gene expression analyses.
The results of those assessments were then used to perform “adaptive randomization” in which the patients were assigned to one of four treatment arms deemed most likely to control their particular malignancy, said Vassiliki Papadimitrakopoulou, MD, professor of medicine in the department of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston, and her associates.
One group of 22 patients received 150 mg erlotinib once daily; the second group (42 patients) received 150 mg erlotinib daily plus 135 mg of the AKT inhibitor MK-2206 once weekly; the third group (75 patients) received 100 mg per week of MK-2206 plus 100 mg of the MEK inhibitor AZD6244 once daily; and the fourth group (61 patients) received 400 mg of sorafenib twice daily. A total of 186 patients were evaluable at 8 weeks, and the overall rate of disease control was 48% at that time. After a median follow-up of 20 months, the median progression-free survival was 2.0 months, median overall survival was 6.5 months, and the 1-year survival was 28%.
The primary endpoint of the study – disease control rate at 8 weeks – was not significantly different among the four treatment groups. It was 32% in group 1, 50% in group 2, 53% in group 3, and 46% in group 4. There were no complete responses and only 6 partial responses: 3 patients in group 3 and 3 patients in group 4. However, the study demonstrated “the utility of real-time biopsies for broad profiling of tumors that serve as a discovery vehicle for better target selection,” the investigators said (J Clin Oncol. 2016 Aug 1. doi:10.1200/JCO.2015.66.0084).
“We are currently pursuing alternative strategies in targeting KRAS mut+ tumors by incorporating knowledge derived from BATTLE 2,” they added.
This study was supported by Merck, Bayer Healthcare Pharmaceuticals, and the National Cancer Institute. Dr. Papadimitrakopoulou and her associates reported ties to numerous industry sources.
“Notwithstanding the low bar of the relatively unconventional endpoint of 8-week [disease control rate], BATTLE-2 should be recognized as a valuable contribution to the field, despite it failing to demonstrate encouraging efficacy in any of the treatment arms or patient subsets,” Howard (Jack) West, MD, wrote in an accompanying editorial (J Clin Oncol. 2016 Aug 1. doi: 10.1200/JCO.2016.68.8226).
But the main result of this study was that all treatment arms produced a disappointing 8-week disease control rate averaging 48%, with no treatment proving to be more promising than the others, with no complete responses and only rare partial responses, and with a progression-free survival of only 2 months in every group, he wrote. However, molecular targeting sometimes benefits small subgroups of patients, such as when advanced squamous NSCLC responds to afatinib. In this study, a subgroup of 52 patients whose tumors showed KRAS mut+ mutations had a significantly longer progression-free survival if they did not receive erlotinib.
Dr. West is affiliated with the Swedish Cancer Institute, Seattle. He reported ties to numerous industry sources.
“Notwithstanding the low bar of the relatively unconventional endpoint of 8-week [disease control rate], BATTLE-2 should be recognized as a valuable contribution to the field, despite it failing to demonstrate encouraging efficacy in any of the treatment arms or patient subsets,” Howard (Jack) West, MD, wrote in an accompanying editorial (J Clin Oncol. 2016 Aug 1. doi: 10.1200/JCO.2016.68.8226).
But the main result of this study was that all treatment arms produced a disappointing 8-week disease control rate averaging 48%, with no treatment proving to be more promising than the others, with no complete responses and only rare partial responses, and with a progression-free survival of only 2 months in every group, he wrote. However, molecular targeting sometimes benefits small subgroups of patients, such as when advanced squamous NSCLC responds to afatinib. In this study, a subgroup of 52 patients whose tumors showed KRAS mut+ mutations had a significantly longer progression-free survival if they did not receive erlotinib.
Dr. West is affiliated with the Swedish Cancer Institute, Seattle. He reported ties to numerous industry sources.
“Notwithstanding the low bar of the relatively unconventional endpoint of 8-week [disease control rate], BATTLE-2 should be recognized as a valuable contribution to the field, despite it failing to demonstrate encouraging efficacy in any of the treatment arms or patient subsets,” Howard (Jack) West, MD, wrote in an accompanying editorial (J Clin Oncol. 2016 Aug 1. doi: 10.1200/JCO.2016.68.8226).
But the main result of this study was that all treatment arms produced a disappointing 8-week disease control rate averaging 48%, with no treatment proving to be more promising than the others, with no complete responses and only rare partial responses, and with a progression-free survival of only 2 months in every group, he wrote. However, molecular targeting sometimes benefits small subgroups of patients, such as when advanced squamous NSCLC responds to afatinib. In this study, a subgroup of 52 patients whose tumors showed KRAS mut+ mutations had a significantly longer progression-free survival if they did not receive erlotinib.
Dr. West is affiliated with the Swedish Cancer Institute, Seattle. He reported ties to numerous industry sources.
Biomarker-driven targeted therapy was found feasible for heavily pretreated, metastatic non–small-cell lung cancer in a phase II trial reported online Aug. 1 in the Journal of Clinical Oncology.
The open-label multicenter umbrella study under the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, called the BATTLE-2, involved 200 patients with advanced NSCLC refractory to platinum-based chemotherapy and multiple other treatments. All patients underwent tumor tissue biopsies for biomarker and gene expression analyses.
The results of those assessments were then used to perform “adaptive randomization” in which the patients were assigned to one of four treatment arms deemed most likely to control their particular malignancy, said Vassiliki Papadimitrakopoulou, MD, professor of medicine in the department of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston, and her associates.
One group of 22 patients received 150 mg erlotinib once daily; the second group (42 patients) received 150 mg erlotinib daily plus 135 mg of the AKT inhibitor MK-2206 once weekly; the third group (75 patients) received 100 mg per week of MK-2206 plus 100 mg of the MEK inhibitor AZD6244 once daily; and the fourth group (61 patients) received 400 mg of sorafenib twice daily. A total of 186 patients were evaluable at 8 weeks, and the overall rate of disease control was 48% at that time. After a median follow-up of 20 months, the median progression-free survival was 2.0 months, median overall survival was 6.5 months, and the 1-year survival was 28%.
The primary endpoint of the study – disease control rate at 8 weeks – was not significantly different among the four treatment groups. It was 32% in group 1, 50% in group 2, 53% in group 3, and 46% in group 4. There were no complete responses and only 6 partial responses: 3 patients in group 3 and 3 patients in group 4. However, the study demonstrated “the utility of real-time biopsies for broad profiling of tumors that serve as a discovery vehicle for better target selection,” the investigators said (J Clin Oncol. 2016 Aug 1. doi:10.1200/JCO.2015.66.0084).
“We are currently pursuing alternative strategies in targeting KRAS mut+ tumors by incorporating knowledge derived from BATTLE 2,” they added.
This study was supported by Merck, Bayer Healthcare Pharmaceuticals, and the National Cancer Institute. Dr. Papadimitrakopoulou and her associates reported ties to numerous industry sources.
Biomarker-driven targeted therapy was found feasible for heavily pretreated, metastatic non–small-cell lung cancer in a phase II trial reported online Aug. 1 in the Journal of Clinical Oncology.
The open-label multicenter umbrella study under the Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (BATTLE) trial, called the BATTLE-2, involved 200 patients with advanced NSCLC refractory to platinum-based chemotherapy and multiple other treatments. All patients underwent tumor tissue biopsies for biomarker and gene expression analyses.
The results of those assessments were then used to perform “adaptive randomization” in which the patients were assigned to one of four treatment arms deemed most likely to control their particular malignancy, said Vassiliki Papadimitrakopoulou, MD, professor of medicine in the department of thoracic/head and neck medical oncology at the University of Texas MD Anderson Cancer Center, Houston, and her associates.
One group of 22 patients received 150 mg erlotinib once daily; the second group (42 patients) received 150 mg erlotinib daily plus 135 mg of the AKT inhibitor MK-2206 once weekly; the third group (75 patients) received 100 mg per week of MK-2206 plus 100 mg of the MEK inhibitor AZD6244 once daily; and the fourth group (61 patients) received 400 mg of sorafenib twice daily. A total of 186 patients were evaluable at 8 weeks, and the overall rate of disease control was 48% at that time. After a median follow-up of 20 months, the median progression-free survival was 2.0 months, median overall survival was 6.5 months, and the 1-year survival was 28%.
The primary endpoint of the study – disease control rate at 8 weeks – was not significantly different among the four treatment groups. It was 32% in group 1, 50% in group 2, 53% in group 3, and 46% in group 4. There were no complete responses and only 6 partial responses: 3 patients in group 3 and 3 patients in group 4. However, the study demonstrated “the utility of real-time biopsies for broad profiling of tumors that serve as a discovery vehicle for better target selection,” the investigators said (J Clin Oncol. 2016 Aug 1. doi:10.1200/JCO.2015.66.0084).
“We are currently pursuing alternative strategies in targeting KRAS mut+ tumors by incorporating knowledge derived from BATTLE 2,” they added.
This study was supported by Merck, Bayer Healthcare Pharmaceuticals, and the National Cancer Institute. Dr. Papadimitrakopoulou and her associates reported ties to numerous industry sources.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Biomarker-driven targeted therapy was found feasible for heavily pretreated, metastatic NSCLC.
Major finding: The primary endpoint – disease control rate at 8 weeks – was 32% in group 1, 50% in group 2, 53% in group 3, and 46% in group 4.
Data source: A randomized open-label phase II study involving 200 patients with heavily pretreated, metastatic NSCLC.
Disclosures: This study was supported by Merck, Bayer Healthcare Pharmaceuticals, and the National Cancer Institute. Dr. Papadimitrakopoulou and her associates reported ties to numerous industry sources.