腫瘤醫學研究所YANG, CHIH-HSINCHIH-HSINYANGCHAO, TSU-YITSU-YICHAO2012-07-122018-07-092012-07-122018-07-092011http://ntur.lib.ntu.edu.tw//handle/246246/241824PURPOSE: The results of the Iressa Pan-Asia Study (IPASS), which compared gefitinib and carboplatin/paclitaxel in previously untreated never- smokers and light ex-smokers with advanced pulmonary adenocarcinoma were published previously . This report presents overall survival (OS) and efficacy according to epidermal growth factor receptor (EGFR) biomarker status. PATIENTS AND METHODS: In all, 1,217 patients were randomly assigned. Biomarkers analyzed were EGFR mutation (amplification mutation refractory system; 437 patients evaluable), EGFR gene copy number ( fluorescent in situ hybridization; 406 patients evaluable), and EGFR protein expression (immunohistochemistry; 365 patients evaluable). OS analysis was performed at 78% maturity. A Cox proportional hazards model was used to assess biomarker status by randomly assigned treatment interactions for progression-free survival (PFS) and OS. RESULTS: OS (954 deaths) was similar for gefitinib and carboplatin/paclitaxel with no significant difference between treatments overall ( hazard ratio [HR], 0. 90; 95% CI, 0.79 to 1.02; P = .109) or in EGFR mutation-positive (HR, 1.00 ; 95% CI, 0.76 to 1.33; P = .990) or EGFR mutation-negative (HR, 1.18; 95% CI, 0.86 to 1.63; P = .309; treatment by EGFR mutation interaction P = . 480) subgroups. A high proportion (64.3%) of EGFR mutation-positive patients randomly assigned to carboplatin/ paclitaxel received subsequent EGFR tyrosine kinase inhibitors. PFS was significantly longer with gefitinib for patients whose tumors had both high EGFR gene copy number and EGFR mutation (HR, 0.48; 95% CI, 0.34 to 0.67) but significantly shorter when high EGFR gene copy number was not accompanied by EGFR mutation (HR, 3.85; 95% CI, 2.09 to 7.09). CONCLUSION: EGFR mutations are the strongest predictive biomarker for PFS and tumor response to first- line gefitinib versus carboplatin/paclitaxel. The predictive value of EGFR gene copy number was driven by coexisting EGFR mutation (post hoc analysis). Treatment-related differences observed for PFS in the EGFR mutation-positive subgroup were not apparent for OS. OS results were likely confounded by the high proportion of patients crossing over to the alternative treatment.en-US[SDGs]SDG3