Phase III, randomized, open-label, first-line study of gefitinib (G) versus carboplatin/paclitaxel (C/P) in selected patients (pts) with advanced non-small cell lung cancer (NSCLC) (IPASS): Evaluation of recruits in Japan
Authors: Y. Ohe, Y. Ichinose, Y. Nishiwaki, N. Yamamoto, S. Negoro, E. Duffield, H. Jiang, N. Saijo, T. Mok, M. Fukuoka
Journal: Journal of Clinical Oncology (2009)

8044^ Background: The IRESSA Pan Asia Study (IPASS) demonstrated superiority of G vs C/P in 1,217 clinically selected chemonaïve pts in Asia with advanced NSCLC. PFS favored C/P initially then G, likely driven by different outcomes according to EGFR mutation (M) status. We report the planned analyses of 233 recruits in Japan (19% of overall population). Methods: From Mar 06 to Oct 07, chemonaïve, never/light ex-smokers with stage IIIB/IV NSCLC and adenocarcinoma histology were randomized to G 250 mg/day (n=114) or C (AUC 5 or 6)/P (200 mg/m 2 ) (n=119). Primary objective was PFS in ITT population; a treatment by country interaction test (Japan vs other) was performed. Secondary endpoints were overall survival (OS), objective response rate (ORR, RECIST), QoL (FACT-L, TOI), symptom improvement (LCS subscale of FACT-L), and tolerability. Results: PFS results in pts in Japan did not significantly differ from other pts (interaction test p=0.4736). G demonstrated superior PFS compared with C/P (HR 0.69; 95% CI 0.51–0.94; p=0.0191); effect was not constant over time, favoring C/P initially then G. Preliminary OS (25% maturity; follow-up ongoing) was similar for G and C/P (HR 0.89; 95% CI 0.53–1.48). ORR for G was 41% vs 35% for C/P;odds ratio [OR] 1.34; 95% CI 0.78–2.30; p=0.2967. QoL improvement rate (TOI) was 43% for G and 28% for C/P (OR 1.92; 95% CI 1.11–3.34; p=0.0200); QoL (FACT-L 41 vs 43%; OR 0.94; 95% CI 0.56–1.60; p=0.8263) and symptom (LCS 42 vs 46%; OR 0.85; 95% CI 0.50–1.43; p=0.5340) improvement rates were similar for G and C/P. Tolerability profile was more favorable with G than C/P. There were no deaths due to ILD-type events (frequency 1.8% [G] vs 0% [C/P]). Conclusions: Efficacy and safety data for pts in Japan were generally consistent with overall population. G demonstrated improved PFS and ORR, similar OS, higher QoL (TOI) and similar symptom improvement rates, and a more favorable tolerability profile compared with C/P in chemonaïve, never/light ex-smokers with advanced NSCLC and adenocarcinoma histology. In IPASS, EGFR M status appeared to be a strong predictive biomarker for G efficacy compared with C/P. [Table: see text] ASCO Conflict of Interest Policy and Exceptions In compliance with the guidelines established by the ASCO Conflict of Interest Policy (J Clin Oncol. 2006 Jan 20;24[3]:519–521) and the Accreditation Council for Continuing Medical Education (ACCME), ASCO strives to promote balance, independence, objectivity, and scientific rigor through disclosure of financial and other interests, and identification and management of potential conflicts. According to the ASCO Conflict of Interest Policy, the following financial and other relationships must be disclosed: employment or leadership position, consultant or advisory role, stock ownership, honoraria, research funding, expert testimony, and other remuneration (J Clin Oncol. 2006 Jan 20;24[3]:520). The ASCO Conflict of Interest Policy disclosure requirements apply to all authors who submit abstracts to the Annual Meeting. For clinical trials that began accrual on or after April 29, 2004, ASCO's Policy places some restrictions on the financial relationships of principal investigators (J Clin Oncol. 2006 Jan 20;24[3]:521). If a principal investigator holds any restricted relationships, his or her abstract will be ineligible for placement in the 2009 Annual Meeting unless the ASCO Ethics Committee grants an exception. Among the circumstances that might justify an exception are that the principal investigator (1) is a widely acknowledged expert in a particular therapeutic area; (2) is the inventor of a unique technology or treatment being evaluated in the clinical trial; or (3) is involved in international clinical oncology research and has acted consistently with recognized international standards of ethics in the conduct of clinical research. NIH-sponsored trials are exempt from the Policy restrictions. Abstracts for which authors requested and have been granted an exception in accordance with ASCO's Policy are designated with a caret symbol (^) in the Annual Meeting Proceedings. For more information about the ASCO Conflict of Interest Policy and the exceptions process, please visit www.asco.org/conflictofinterest .