Wu Y.-LSaijo NThongprasert SCHIH-HSIN YANGHan BMargono BChewaskulyong BSunpaweravong POhe YIchinose YYang J.-JMok T.S.KYoung HHaddad VRukazenkov YFukuoka M.2020-05-262020-05-2620170169-5002https://www.scopus.com/inward/record.uri?eid=2-s2.0-85009789298&doi=10.1016%2fj.lungcan.2016.11.022&partnerID=40&md5=4251f94508ee6fd7315f0dce47fe1959https://scholars.lib.ntu.edu.tw/handle/123456789/494954Objective The Phase III, randomized, open-label IPASS study (NCT00322452) of first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) gefitinib versus carboplatin/paclitaxel for Asian patients with advanced non-small-cell lung cancer (NSCLC) showed that investigator-assessed progression-free survival (PFS) and objective response rate (ORR) were significantly prolonged in patients with EGFR mutation-positive NSCLC who received gefitinib versus patients with EGFR mutation-negative NSCLC. We report post-hoc analyses of IPASS data by blind independent central review (BICR), performed at the request of the US FDA, in a subset of patients with EGFR mutation-positive NSCLC. Patients and methods Eligible patients (aged ?18 years; histologically/cytologically confirmed Stage IIB/IV adenocarcinoma NSCLC; non- or former light-smokers; treatment-na?ve) were randomly assigned 1:1 to gefitinib (250 mg/day) or carboplatin (dose calculated to produce an area under the curve of 5 or 6 mg/mL/minute)/paclitaxel (200 mg/m2). Primary endpoint: PFS. BICR analyses included PFS, ORR, and duration of response (DoR). Results Scans from 186 IPASS patients (gefitinib n = 88, carboplatin/paclitaxel n = 98) with EGFR mutation-positive NSCLC were available for BICR. Consistent with investigator-assessed results, in patients with EGFR mutation-positive NSCLC: PFS (hazard ratio 0.54; 95% confidence interval [CI] 0.38, 0.79; p = 0.0012) and ORR (odds ratio 3.00; 95% CI 1.63, 5.54; p = 0.0004) were significantly longer with gefitinib versus carboplatin/paclitaxel. The median DoR by BICR was 9.6 months with gefitinib and 5.5 months with carboplatin/paclitaxel. Conclusion BICR analysis of IPASS data support the original, investigator-assessed results. EGFR mutation-positive status remains a significant predictor of response to first-line TKI therapy. ? 2016 The AuthorsEpidermal growth factor receptor tyrosine kinase inhibitor; Epidermal growth factor receptor-mutation positive; IPASS study; Non-small-cell lung cancer[SDGs]SDG3carboplatin; epidermal growth factor receptor; gefitinib; paclitaxel; antineoplastic agent; carboplatin; epidermal growth factor receptor; gefitinib; paclitaxel; protein kinase inhibitor; quinazoline derivative; adult; advanced cancer; aged; Article; Asian; cancer combination chemotherapy; cancer staging; cancer survival; drug efficacy; female; food and drug administration; gene mutation; histopathology; human; lung adenocarcinoma; major clinical study; male; multicenter study (topic); multiple cycle treatment; open study; phase 3 clinical trial (topic); post hoc analysis; priority journal; progression free survival; randomized controlled trial (topic); smoking; treatment response; adenocarcinoma; Asian continental ancestry group; Carcinoma, Non-Small-Cell Lung; clinical trial; disease free survival; epidemiology; genetics; Lung Neoplasms; middle aged; multicenter study; mutation; pathology; phase 3 clinical trial; very elderly; Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Asian Continental Ancestry Group; Carboplatin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Female; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Neoplasm Staging; Paclitaxel; Protein Kinase Inhibitors; Quinazolines; Randomized Controlled Trials as Topic; Receptor, Epidermal Growth Factor; Smokingjournal article10.1016/j.lungcan.2016.11.022282129932-s2.0-85009789298