Abstract 1162
Background
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.
Methods
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.
Results
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%).
Conclusions
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
NCT01469000
Legal entity responsible for the study
Eli Lilly and Company
Funding
Eli Lilly and Company
Disclosure
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.