Non-small cell lung cancer, metastatic

ABSTRACT Background Erlotinib (E) and Pemetrexed (P) are approved second-line treatments in patients (pts) with relapsed NSCLC and may be effective in combination. This randomized phase 2 study compared the efficacy and safety of E + P vs either agent alone, as second-line treatment in never-smoker pts with advanced non-squamous NSCLC. Methods From Nov 2007 to Jul 2010, never-smoker NSCLC, ECOG Performance Status (PS) ≤2 pts who had failed 1 prior chemotherapy regimen were enrolled and randomized to either: E 150 mg daily, P 500 mg/m2 day 1, or P 500 mg/m2 day 1 plus E 150 mg daily on days 2 to 14 of a 21-day cycle, continued until discontinuation criteria were met. The primary endpoint of progression-free survival (PFS) was analyzed using a sequential approach. A multivariate Cox model was used to perform a global comparison across the 3 arms with pairwise comparisons between treatments using contrasts within the model. If the global null hypothesis was rejected at a 2-sided 0.2 significance level (SL), then 2 pairwise comparisons of E + P vs E or P were conducted. Statistical significance was claimed if both pairwise and global null hypotheses were rejected at a 2-sided 0.05 SL. Results A total of 240 non-squamous pts (Male, 34.6%; East Asian, 55.4%; ECOG PS 0-1, 92.9%) were included. A statistically significant difference in PFS was found across the 3 arms (global p = 0.003), with E + P significantly better than both single agents (HR (95% CI) for E + P vs E was 0.57 (0.40, 0.81), p = 0.002; for E + P vs P was 0.58 (0.39, 0.85), p = 0.005). Median PFS (95% CI) was 7.4 months (4.4, 12.9) in E + P, 3.8 (2.7, 6.3) in E and 4.4 (3.0, 6.0) in P. Safety analyses showed a higher number of pts with ≥1 TEAE with CTCAE grade 3/4 toxicity in E + P (n = 45; 60.0%) than in P (n = 10; 28.9%) or E (n = 22; 12.0%), the majority being neutropenia, anemia, rash and diarrhea. Conclusions Erlotinib + Pemetrexed significantly improved PFS compared to either agent alone in this clinically selected population. E + P had more toxicity, but was clinically manageable. Further analysis of the EGFR mutational status will help to understand and predict which pts will benefit most from this approach. Disclosure X. Wang: I am employee of Eli Lilly and Company. S. Altug: I am employee of, and hold stock/stock options in, Eli Lilly and Company. M. Orlando: “I am employed by and hold stock in Eli Lilly & Company”. All other authors have declared no conflicts of interest.