First-line treatment (txt) with pemetrexed-cisplatin (PC), followed sequentially by gefitinib (G) or pemetrexed, in Asian, never-smoker (n/smkr) patients (pts) with advanced NSCLC: An open-label, randomized phase II trial.

Abstract

7591 Background: Asian, n/smkr NSCLC pts show more favorable clinical course and improved outcomes when treated with EGFR-TKIs or chemo, particularly in presence of EGFR mutations (mut). In unknown EGFR mut status pts, optimal selection/integration of both modalities is unclear. This trial compared first-line sequential (seq) txt with PC followed by either G or P. Methods: Asian, n/smkr, chemonaive, stage IIIB/IV NSCLC and ECOG PS ≤1 pts, of unknown EGFR mut status, were randomized to Arm A (4 cycles: P[500 mg/m2] + C[75 mg/m2] q3 wks followed by G [250 mg/d]) or Arm B (induction chemo per Arm A followed by P [500 mg/m2] q3 wks [+C, max 2 additional cycles]). While progression-free survival (PFS) was calculated from randomization, the primary objective was a comparison during the seq phase only (ie, from cycle 5) by a time-dependent Cox model. Tissue collection for EGFR mut analysis was optional. Results: Primary endpoint analysis results are presented. Between (btwn) Feb-Nov 2007, 70 pts from China, Korea and Taiwan received induction PC. Baseline characteristics were balanced btwn arms. 49 pts (70.0%) received seq txt (n=25 G; n=24 P), while 21 pts (30.0%) discontinued during induction. The primary endpoint indicates pts on seq G have significantly lower risk of progression and PFS overall indicates a trend favoring Arm A. Response was not statistically different btwn txt arms, yet duration of response was improved in Arm A. Survival was consistently higher for Arm B pts. No significant difference was observed btwn txt arms for grade 3/4/5 toxicities. Conclusions: Pts receiving first-line PC followed by seq G showed prolonged PFS, in excess of 9 mths. OS, although immature, is encouraging regardless of seq txt choice. Evaluation of txt sequence according to EGFR mut status in NSCLC pts is warranted. Arm A Arm B Induction PC (N=39)Seq G (N=25) Induction PC (N=31)Seq P (N=24) HR (95% CI); p value PFS HR seq phase only 0.194 (0.075, 0.502); <0.001 PFS HR overall 0.533 (0.272, 1.044); 0.067 PFS median mths (95% CI) 9.95 (5.85, 16.49) 6.83 (5.78, 7.98) Overall survival (OS), % 12 mths 74.8 93.3 24 mths 59.6 71.1 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Lilly Lilly