Hongyun Zhao1, Yun Fan, Shenglin Ma, Xiangqun Song, Baohui Han, Ying Cheng, Cheng Huang, Shujun Yang, Xiaoqing Liu, Yunpeng Liu, Shun Lu, Jie Wang, Shucai Zhang, Caicun Zhou, Mengzhao Wang, Li Zhang. 1. *Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangzhou, China †Department of Medical Oncology, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China; ‡Department of Medical Oncology, Sun-Yat Sen University Cancer Center, Guangzhou, China; §Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China; ‖Department of Radiation Therapy, Hangzhou First Pepole's Hospital, Hangzhou, China; ¶Department of Medical Oncology, Guangxi Zhuang Autonomous Region Tumour Hospital, Nanning City, China; #Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai, China; **Department of Medical Oncology, Jilin Province Tumour Hospital, Changchun, China; ††Department of Respiratory Medicine, Fujian Provincial Tumor Hospital, Fuzhou, China; ‡‡Department of Chemotherapy, Henan Province Tumour Hospital, Zhengzhou, China; §§Department of Oncology, 307 Hospital of The People' Liberation Army, Beijing, China; ‖‖Department of Medical Oncology, First Hospital of China Medical University, Shenyang, China; ¶¶Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, ##Department of Thoracic Medical Oncology, Beijing Cancer Hospital, Beijing, China; ***Department of Medical Oncology, Beijing Chest Hospital, Beijing, China; †††Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China; and ‡‡‡Department of Respiratory Disease, Peking Union Medical College, Beijing, China.
Abstract
BACKGROUND: The results of the Iressa in NSCLC for maintenance study (NCT00770588; C-TONG 0804), which compared gefitinib and placebo as maintenance therapy in patients with advanced non-small-cell lung cancer without disease progression after first-line chemotherapy, were published previously. The objective of this report is to provide a mature analysis of overall survival (OS) for Iressa in NSCLC for maintenance study in intention to treat (ITT) population and in subgroups according to epidermal growth factor receptor (EGFR) mutation status. PATIENTS AND METHODS: A total of 296 patients were randomly assigned. EGFR mutations were detected using an amplification mutation refractory system. Seventy-nine patients were assessable for EGFR mutations. OS was analyzed by a Cox proportional hazards model adjusted for the same covariates in ITT population and subgroups according to EGFR mutation status. RESULTS:OS was similar for gefitinib and placebo arm with no significant difference between treatments in ITT population (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.68-1.14; p = 0.335) and in subgroups with wild type EGFR (HR, 1.27; 95% CI, 0.7-2.3; p = 0.431) or unknown EGFR mutations (HR, 0.92; 95% CI, 0.68, 1.25; p = 0.603). In the EGFR mutation-positive subgroup, the gefitinib arm showed a higher OS than the placebo arm (HR, 0.39; 95% CI, 0.15, 0.97; p = 0.036). CONCLUSION: EGFR mutation was the strongest predictive biomarker for OS benefit of gefitinib as maintenance treatment. The analyses of OS showed that patients achieve a clear and significant survival benefit if they receive EGFR tyrosine kinase inhibitors as maintenance treatment in EGFR mutation-positive patients.
RCT Entities:
BACKGROUND: The results of the Iressa in NSCLC for maintenance study (NCT00770588; C-TONG 0804), which compared gefitinib and placebo as maintenance therapy in patients with advanced non-small-cell lung cancer without disease progression after first-line chemotherapy, were published previously. The objective of this report is to provide a mature analysis of overall survival (OS) for Iressa in NSCLC for maintenance study in intention to treat (ITT) population and in subgroups according to epidermal growth factor receptor (EGFR) mutation status. PATIENTS AND METHODS: A total of 296 patients were randomly assigned. EGFR mutations were detected using an amplification mutation refractory system. Seventy-nine patients were assessable for EGFR mutations. OS was analyzed by a Cox proportional hazards model adjusted for the same covariates in ITT population and subgroups according to EGFR mutation status. RESULTS: OS was similar for gefitinib and placebo arm with no significant difference between treatments in ITT population (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.68-1.14; p = 0.335) and in subgroups with wild type EGFR (HR, 1.27; 95% CI, 0.7-2.3; p = 0.431) or unknown EGFR mutations (HR, 0.92; 95% CI, 0.68, 1.25; p = 0.603). In the EGFR mutation-positive subgroup, the gefitinib arm showed a higher OS than the placebo arm (HR, 0.39; 95% CI, 0.15, 0.97; p = 0.036). CONCLUSION:EGFR mutation was the strongest predictive biomarker for OS benefit of gefitinib as maintenance treatment. The analyses of OS showed that patients achieve a clear and significant survival benefit if they receive EGFR tyrosine kinase inhibitors as maintenance treatment in EGFR mutation-positive patients.