The primary analysis of this open-label, randomized, multicenter, phase 2 study found significantly longer progression-free survival (PFS) for pemetrexed plus gefitinib (P + G) vs gefitinib alone (G) in 191 East Asian patients with EGFR mt+ NS NSCLC (adjusted hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.48-0.96; P = 0.029). Translational research, interim OS data and updated safety results are reported.
Treatment-naive patients with advanced, EGFR mt+ (local laboratory testing), NS NSCLC were randomized (2:1) to receive P + G (pemetrexed 500 mg/m2, Day 1 of 21-day cycles plus gefitinib 250 mg/day; n = 126) or G (gefitinib 250 mg/day; n = 65). Mandatory pretreatment tissue samples were assayed for EGFR mutations by central evaluation (CE) (n = 159) and thymidylate synthase (TS) by immunohistochemistry (n = 146). OS in the intention-to treat (ITT) population and correlation of biomarkers with clinical outcomes were analyzed by adjusted Cox regression.
By CE, 149/159 patients (93.7%) were EGFR mt+. In the CE+ population, PFS was longer for P + G (n = 96) vs G (n = 53) (HR: 0.72; 95% CI: 0.48-1.06; P = 0.093), consistent with the primary analysis based on local testing. In patients with low (n = 67) and high (n = 79) TS expression, the PFS HR was 0.47 (95% CI: 0.26-0.87) and 0.83 (95% CI: 0.47-1.46), respectively; the interaction effect was not statistically significant (P = 0.177). At the interim OS analysis (80 events, 58% censoring), OS was not significantly different for P + G vs G (HR: 0.79; 95% CI: 0.49-1.28; P = 0.342). Postdiscontinuation systemic therapy was common (P + G: 62.7%; G: 72.3%). The incidence of grade 3/4 drug-related adverse events was significantly (P = 0.002) higher for P + G (42.9%) vs G (20.0%).
The PFS HR for the CE+ population was consistent with the primary ITT analysis. No significant interaction effects were seen for TS. At this interim analysis, there was no statistical difference in OS for P + G vs G. Final OS analyses will be reported when 130 events have occurred.
Clinical trial identification
Legal entity responsible for the study
Eli Lilly and Company
Eli Lilly and Company
J. Yang: Astrazeneca, Roche, Eli Lilly, Boehringer Ingelheim, Pfizer, Clovis Oncology, Novartis, Bayer, MSD, Merck, Astellas, Daichi-Sankyo, Celgene. H. Murakami: Research funding from Eli Lilly, Kyowa Kirin, Chu-gai, AstraZeneca, Novartis., Astellas, Taiho, Quintiles Transnational, Clovis Oncology. Honoraria from Boehringer-ingelheim, Pfizer, Chu-gai, Taiho, Nippon Kayaku, Clovis Oncology. K. Nakagawa: Honoraria received from Eli Lilly Japan K.K., Daiichi Sankyo Co., Ltd. Speakers Bureau from Eli Lilly Japan K.K. /Daiichi Sankyo Co., Ltd. Grants/Research Support received from Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd. J.H. Kang: Advisory Board member for Eli Lilly and Company. J-H. Kim: Consulted/advised for Eli Lilly and Company. R. Hozak, T. Nguyen, X. Wang, T. Puri, M. Orlando, S. Enatsu: Employee and shareholder of Eli Lilly and Company. All other authors have declared no conflicts of interest.