1240P - Randomized phase 2 trial of gefitinib with and without pemetrexed as first-line therapy in East Asian patients with advanced, epidermal growth fact...

Date 08 October 2016
Event ESMO 2016 Congress
Session Poster Display
Topics Cytotoxic agents
Non-small-cell lung cancer
Therapy
Biological therapy
Presenter James Yang
Citation Annals of Oncology (2016) 27 (6): 416-454. 10.1093/annonc/mdw383
Authors J. Yang1, Y. Cheng2, H. Murakami3, P. Yang4, J. He5, K. Nakagawa6, J.H. Kang7, J. Kim8, R. Hozak9, T. Nguyen10, X. Wang11, S. Enatsu12, T. Puri13, M. Orlando14
  • 1Department Of Oncology, National Taiwan University Hospital, 100 - Taipei/TW
  • 2Department Of Medical Oncology, Jilin Province Cancer Hospital, 130012 - Changchun/CN
  • 3Department Of Oncology, Shizuoka Cancer Center, Shizuoka/JP
  • 4Department Of Oncology, National Taiwan University Hospital, Taipei/TW
  • 5Department Of Thoracic Oncology, The 1st Affiliated Hospital of Guangzhou Medical University, 510120 - Guangzhou/CN
  • 6Department Of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama/JP
  • 7Department Of Medical Oncology, The Catholic University of Korea, 137-701 - Seoel/KR
  • 8Department Of Oncology, CHA Bundang Medical Center, CHA University, Gyeonggi-do/KP
  • 9Oncology Business Unit, Eli Lilly and Company, Indianapolis/US
  • 10Oncology Tailoring Biomarker Statistics, Eli Lilly and Company, Indianapolis/US
  • 11Medicines Development Unit, Eli Lilly and Company, Shanghai/CN
  • 12Medicines Development Unit, Eli Lilly Japan K.K., Kobe/JP
  • 13Medical Affairs, Eli Lilly and Company, Gurgaon/IN
  • 14Emerging Markets Medical Affairs, Eli Lilly and Company, Buenos Aire/AR

Abstract

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.