Fukuoka MWu Y.-LThongprasert SSunpaweravong PLeong S.-SSriuranpong VChao T.-YNakagawa KChu D.-TSaijo NDuffield E.LRukazenkov YSpeake GJiang HArmour A.ATo K.-FCHIH-HSIN YANGMok T.S.K.2020-05-262020-05-2620110732-183Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-79960702788&doi=10.1200%2fJCO.2010.33.4235&partnerID=40&md5=485a8451af0938c501fb022ee3c0bf1dhttps://scholars.lib.ntu.edu.tw/handle/123456789/495076Purpose: 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. ? 2011 by American Society of Clinical Oncology.[SDGs]SDG3biological marker; carboplatin; epidermal growth factor receptor; gefitinib; paclitaxel; adult; advanced cancer; aged; cancer combination chemotherapy; cancer patient; cancer survival; conference paper; drug efficacy; female; gene dosage; gene mutation; human; lung non small cell cancer; major clinical study; male; monotherapy; multiple cycle treatment; open study; overall survival; phase 3 clinical trial; priority journal; progression free survival; protein expression; randomized controlled trial; treatment outcome; Adenocarcinoma; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Asia; Carboplatin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Female; Gene Dosage; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Individualized Medicine; Kaplan-Meier Estimate; Logistic Models; Lung Neoplasms; Male; Middle Aged; Mutation; Odds Ratio; Paclitaxel; Patient Selection; Predictive Value of Tests; Proportional Hazards Models; Protein Kinase Inhibitors; Quinazolines; Receptor, Epidermal Growth Factor; Risk Assessment; Risk Factors; Survival Rate; Time Factors; Treatment Outcome; Tumor Markers, Biologicalconference paper10.1200/JCO.2010.33.4235216704552-s2.0-79960702788