PMID- 21670455 OWN - NLM STAT- MEDLINE DCOM- 20110916 LR - 20220419 IS - 1527-7755 (Electronic) IS - 0732-183X (Linking) VI - 29 IP - 21 DP - 2011 Jul 20 TI - Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). PG - 2866-74 LID - 10.1200/JCO.2010.33.4235 [doi] AB - PURPOSE: 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. FAU - Fukuoka, Masahiro AU - Fukuoka M AD - Kinki University School of Medicine, Osaka, Japan. FAU - Wu, Yi-Long AU - Wu YL FAU - Thongprasert, Sumitra AU - Thongprasert S FAU - Sunpaweravong, Patrapim AU - Sunpaweravong P FAU - Leong, Swan-Swan AU - Leong SS FAU - Sriuranpong, Virote AU - Sriuranpong V FAU - Chao, Tsu-Yi AU - Chao TY FAU - Nakagawa, Kazuhiko AU - Nakagawa K FAU - Chu, Da-Tong AU - Chu DT FAU - Saijo, Nagahiro AU - Saijo N FAU - Duffield, Emma L AU - Duffield EL FAU - Rukazenkov, Yuri AU - Rukazenkov Y FAU - Speake, Georgina AU - Speake G FAU - Jiang, Haiyi AU - Jiang H FAU - Armour, Alison A AU - Armour AA FAU - To, Ka-Fai AU - To KF FAU - Yang, James Chih-Hsin AU - Yang JC FAU - Mok, Tony S K AU - Mok TS LA - eng PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PT - Webcast DEP - 20110613 PL - United States TA - J Clin Oncol JT - Journal of clinical oncology : official journal of the American Society of Clinical Oncology JID - 8309333 RN - 0 (Antineoplastic Agents) RN - 0 (Biomarkers, Tumor) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinazolines) RN - BG3F62OND5 (Carboplatin) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - P88XT4IS4D (Paclitaxel) RN - S65743JHBS (Gefitinib) SB - IM CIN - J Clin Oncol. 2011 Jul 20;29(21):2843-4. doi: 10.1200/JCO.2011.35.9208. PMID: 21670452 MH - Adenocarcinoma/chemistry/*drug therapy/genetics/mortality/pathology MH - Adenocarcinoma of Lung MH - Aged MH - Antineoplastic Agents/*therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Asia MH - Biomarkers, Tumor/*analysis/genetics MH - Carboplatin/administration & dosage MH - Carcinoma, Non-Small-Cell Lung/chemistry/*drug therapy/genetics/mortality/pathology MH - Disease-Free Survival MH - ErbB Receptors/*analysis/antagonists & inhibitors/genetics MH - Female MH - Gefitinib MH - Gene Dosage MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Kaplan-Meier Estimate MH - Logistic Models MH - Lung Neoplasms/chemistry/*drug therapy/genetics/mortality/pathology MH - Male MH - Middle Aged MH - Mutation MH - Odds Ratio MH - Paclitaxel/administration & dosage MH - Patient Selection MH - Precision Medicine MH - Predictive Value of Tests MH - Proportional Hazards Models MH - Protein Kinase Inhibitors/*therapeutic use MH - Quinazolines/*therapeutic use MH - Risk Assessment MH - Risk Factors MH - Survival Rate MH - Time Factors MH - Treatment Outcome EDAT- 2011/06/15 06:00 MHDA- 2011/09/17 06:00 CRDT- 2011/06/15 06:00 PHST- 2011/06/15 06:00 [entrez] PHST- 2011/06/15 06:00 [pubmed] PHST- 2011/09/17 06:00 [medline] AID - JCO.2010.33.4235 [pii] AID - 10.1200/JCO.2010.33.4235 [doi] PST - ppublish SO - J Clin Oncol. 2011 Jul 20;29(21):2866-74. doi: 10.1200/JCO.2010.33.4235. Epub 2011 Jun 13.