Biomarker analyses from a phase III, randomized, open-label, first-line study of gefitinib (G) versus carboplatin/paclitaxel (C/P) in clinically selected patients (pts) with advanced non-small cell lung cancer (NSCLC) in Asia (IPASS).
M. Fukuoka, Y. Wu, S. Thongprasert, C. Yang, D. Chu, N. Saijo, C. Watkins, E. Duffield, A. Armour, T. Mok
Background: IPASS demonstrated overall superiority of first-line G vs C/P for progression-free survival (PFS) in never/light ex-smokers with stage IIIB/IV adenocarcinoma NSCLC in Asia. PFS favored CP initially and then G. Outcome was correlated with biomarkers (preplanned exploratory objective).
Methods: 683 patients provided tissue samples. Analyses included primary endpoint PFS (Cox proportional hazards) and secondary endpoint objective response rate (ORR; logistic regression) by biomarker status.
Results: EGFR mutation (M) status was evaluable in 437 pts by Amplification Refractory Mutation System (ARMS; 60% M+). M+ pts had significantly longer PFS and higher ORR and M- pts significantly shorter PFS and lower ORR with G than C/P. In M unknown pts PFS and ORR were similar to overall population. Post hoc analysis of overall survival favored G in M+ pts (31% maturity; HR 0.78; 95% CI 0.50-1.20) and C/P in M- pts (53% maturity; HR 1.38; 95% CI 0.92-2.90); differences were not statistically significant and follow-up is ongoing. EGFR gene-copy number was evaluable in 406 pts by fluorescence in situ hybridization (FISH; 61% FISH +). Similar PFS and ORR results to analyses by M status were observed, driven by the overlap in EGFR FISH and M status. EGFR protein expression (PE) was evaluable in 365 pts by immunohistochemistry (73% PE+). PFS outcomes did not differ statistically between PE+ and PE-. ORR favored G in both PE+ and - pts.
Conclusions: EGFR M status was a strong predictive biomarker for the efficacy of G vs C/P in this clinically selected first-line setting.
编辑: ludongcn 作者:丁香园通讯员