931MO - Final overall survival analysis of phase III study of pemetrexed/cisplatin versus vinorelbine/cisplatin for completely resected non-squamous non-small cell lung cancer: The JIPANG Study

Background

The JIPANG study has demonstrated pemetrexed/cisplatin (Pem/Cis) had a similar efficacy on recurrence-free survival (RFS) to vinorelbine/cisplatin (Vnr/Cis) with a better tolerability as postoperative adjuvant chemotherapy for patients with completely resected non-squamous non-small-cell lung cancer (Ns-NSCLC). Overall survival (OS) is one of secondary endpoints in this trial. The final analysis of OS in the JIPANG study is presented here. An interaction between treatment regimen and EGFR mutation status for OS is also reported.

Methods

Patients with completely resected pathological stage II-IIIA Ns-NSCLC were randomized in a 1:1 ratio to receive either Pem (500 mg/m², day 1)/Cis (75 mg/m², day 1) or Vnr (25 mg/m², days 1 and 8)/Cis (80 mg/m², day 1), and stratified according to sex, age, pathological stage, EGFR mutation status and institution. This analysis was performed by using data at 5 years after last patient enrollment.

Results

Between March 2012 and August 2016, 804 patients were randomized. Of 783 for the efficacy analysis (389 in Pem/Cis and 394 in Vnr/Cis), median age was 65/65 years; stage IIIA 52/52%; and EGFR mutation, 24/25%. An updated median RFS was 43.4 months (mo) in Pem/Cis and 37.5 mo in Vnr/Cis with a hazard ratio (HR) of 0.95 (95% CI, 0.79—1.14; stratified one-sided log-rank test, P=0.249). With a median follow-up of 77.3 mo, OS rate at 3 and 5 years were 87.0% and 75.0% versus 84.1% and 75.6% with a HR of 1.04 (95% CI, 0.81—1.34, P=0.598). In the subgroup analysis of OS, HRs in patients with and without EGFR mutations were 1.98 (95% CI, 1.13—3.28) and 0.86 (95% CI, 0.64—1.14), respectively (Interaction, P=0.011). Among total of 441 recurrences observed, brain metastasis was reported in patients with EGFR mutations (Pem/Cis; 20 (30.3%), Vnr/Cis; 11 (18.6%)) and in those without EGFR mutations (Pem/Cis; 27 (18.6%), Vnr/Cis; 47 (27.5%)).

Conclusions

This final analysis showed that Pem/Cis had a similar efficacy to Vnr/Cis in both RFS and OS for this population. The OS with adjuvant Pem/Cis or Vnr/Cis was one of the longest observed in these population compared with the historical data, regardless of EGFR mutation status.

Clinical trial identification

UMIN000006737, jRCTs041180023.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Japan Agency for Medical Research and Development (Grant No. 16lk0201005h0005). Pemetrexed for this study was provided by Eli Lilly.

Disclosure

K. Yoh: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol-Myers Squibb, Chugai, Daiichi sankyo, Janssen, Lilly, Taiho, Novartis, Kyowa kirin, Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Lilly, Pfizer, Daiichi sankyo, AbbVie, Taiho, MSD, Takeda. H. Kenmotsu: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co, Ltd., Ono Pharmaceutical Co, Ltd., Boehringer Ingelheim, Eli Lilly K.K, Kyowa Hakko Kirin Co., Ltd., Bristol-Myers Squibb, MSD, Novartis Pharma K.K., Daiichi-Sankyo Co., Ltd., AstraZeneca K.K., Pfizer, Taiho Pharma, Merck, Amgen inc., Bayer, Takeda Pharmaceutical Co., Ltd; Financial Interests, Institutional, Research Grant: AstraZeneca, Chugai Pharmaceutical Co, Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co, Ltd., Loxo Oncology, Eli Lilly K.K; Non-Financial Interests, Principal Investigator: AstraZeneca K.K., Eli Lilly K.K, Boehringer Ingelheim, Takeda Pharmaceutical Co., Ltd. N. Yamamoto: Financial Interests, Personal, Invited Speaker: MSD K.K, AstraZeneca, Ono Pharmaceutical Co., Ltd., Thermo Fisher Scientific, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Boehringer-Ingelheim, Novartis, Pfizer Inc., Bristol-Myers Squibb, Nippon Kayaku, GlaxoSmithKline K.K., Sanofi K.K., Hisamitsu Pharmaceutical Co.,Inc., Merck biopharma; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Boehringer-Ingelheim, Novartis, Bristol-Myers Squibb, Nippon Kayaku, Life Technologies Japan Ltd., Amgen Inc., Guardant Health Japan, Janssen Pharmaceutical K.K.; Financial Interests, Institutional, Research Grant: MSD K.K; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Pfizer Inc., Amgen Inc., Janssen Pharmaceutical K.K.; Financial Interests, Institutional, Funding: Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Toppan printing, Terumo. T. Takahashi: Financial Interests, Personal, Invited Speaker: AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd., Msd K.K., Pfizer Japan Inc., Boehringer Ingelheim Japan, INC, Takeda Pharmaceutical Co Ltd., Yakult Honsha Co. Ltd; Financial Interests, Institutional, Invited Speaker: AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Amgen Inc., Merck Biopharma Co., Ltd. H. Saito: Financial Interests, Institutional, Invited Speaker: AstraZeneca, Chugai Pharmaceutical Co., Ltd., Bristol Myers Squibb, Ono Pharmaceutical Co., Ltd. S. Sugawara: Financial Interests, Personal, Other, Lecture fee: AstraZeneca, Chugai Pharma, Nippon Boehringer Ingelheim, Taiho Pharmaceutical, Pfizer, Lilly, Novartis, Bristol-Myers Squibb, Ono Pharmaceutical, MSD K.K, Yakult Honsha, Kyowa Kirin, Towa Pharmaceutical, Takeda, Nippon Kayaku, Otsuka, Merck, Amgen, Thermo Fisher Scientific, AbbVie. K. Nakagawa: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Nippon Kayaku Co., Ltd., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., MSD K.K., Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co.,Ltd., Bayer Yakuhin, Ltd., CMIC ShiftZero K.K., Life Technologies Japan Ltd., Neo Communication, Merck Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., 3H Clinical Trial Inc., Care Net, Inc., Medical Review Co., Ltd., Medical Mobile Communications co., Ltd, Yodosha Co., Ltd., Nikkei Business Publications, Inc., Japan Clinical Research Operations, CMIC Co., Ltd., Novartis Pharma K.K., Taiyo Pharma Co., Ltd.; Financial Interests, Personal, Advisory Board: Ono Pharmaceutical Co.,Ltd., Eli Lilly Japan K.K.; Financial Interests, Institutional, Other, patents sales fee: Daiichi Sankyo Co., Ltd.; Financial Interests, Institutional, Research Grant: PAREXEL International Corp., PRA Healthsciences, EPS Corporation., Kissei Pharmaceutical Co., Ltd., EPS International Co.,Ltd,., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co.,Ltd., MSD K.K., Ono Pharmaceutical Co.,Ltd., PPD-SNBL K.K, SymBio Pharmaceuticals Limited., Iqvia Services Japan K.K., Syneos Health Clinical K.K., Nippon Kayaku Co.,Ltd., EP-CRSU Co., Ltd., Mebix, Inc., Bristol-Myers Squibb K.K., Janssen Pharmaceutical K.K., Eisai Co., Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Covance Japan Inc., Japan Clinical Research Operations, Takeda Pharmaceutical Co.,Ltd., GlaxoSmithKline K.K., Sanofi K.K., Chugai Pharmaceutical Co.,Ltd., Nippon Boehringer Ingelheim Co.,Ltd., Sysmex Corporation, Medical Reserch Support, Eli Lilly Japan K.K., Amgen Inc., Novartis Pharma K.K., Novartis Pharma K.K., SRL, Inc. K. Sugio: Financial Interests, Institutional, Research Grant: Eli Lilly Japan, Taiho, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi-Sankyo, Covidien Japan. T. Seto: Financial Interests, Personal, Invited Speaker: Eli Lilly Japan, Takeda Pharmaceutical, Chugai Pharmaceutical, Covidien Japan, Mochida Pharmaceutical, MSD, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Towa Pharmaceutical, Eli Lilly Japan; Financial Interests, Personal, Full or part-time Employment: Precision Medicine Asia; Non-Financial Interests, Invited Speaker: West Japan Oncology Group. S. Toyooka: Financial Interests, Institutional, Research Grant: Eli Lilly, AstraZeneca, Taiho, Chugai; Financial Interests, Personal, Invited Speaker: Eli Lilly, AstraZeneca, Taiho, Chugai, Novartis, Ono Pharmaceutical, Boehringer Ingelheim, Astellas Pharma, Daiichi Sankyo, Bayer, Kyorin, Johnson & Johnson, Medtronic. H. Date: Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical. T. Mitsudomi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai, Novartis, MSD, Bristol Myers Squibb, Ono, Pfizer, Eli-Lilly, Merck Biopharma; Financial Interests, Personal, Advisory Board: AsreaZeneca, Boehringer-Ingelheim, Chugai, Novartis, MSD, Bristol Myers Squibb, Ono, Pfiezer, Amgen, Janssen, Takeda, Eli-Lilly; Financial Interests, Institutional, Invited Speaker: Boehringer-Ingelheim, AstraZeneca, Chugai, MSD, Taiho, Daiichi-Sankyo, Ono; Non-Financial Interests, Leadership Role: Interanational Association for Study of Lung Cancer. I. Okamoto: Financial Interests, Institutional, Research Grant: Eli Lilly K.K; Financial Interests, Personal, Invited Speaker: Eli Lilly K.K. H. Okamoto: Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd., Taiho, Astellas, Eli Lilly, Merck BioPharma; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Boehringer Ingelheim, Novartis, Bristol Myers Squibb, Chugai Pharmaceutical Co., Ltd. Y. Takiguchi: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, AstraZeneca, Chugai Pharma, Boehringer Ingelheim, Daiichi Sankyo, Taiho Pharmaceutical, Bristol-Myers Squibb Japan, Lilly, Pfizer, Novartis, Kyowa Kirin International; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Lilly, Taiho Pharmaceutical, Chugai Pharma, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: MSD Oncology, AstraZeneca. M. Tsuboi: Financial Interests, Personal, Invited Speaker, Lecture: Johnson & Johnson Japan; Financial Interests, Personal, Advisory Board, Lectures, Advisory boards: AstraZeneca KK, Chugai Pharmaceutical Co.,Ltd, MSD; Financial Interests, Personal, Invited Speaker, Lectures: Eli Lilly Japan, Bristol-Myers Squibb KK, Teijin Pharma, Taiho Pharma, Medtronic Japan, ONO Pharmaceutical CO.,LTD; Financial Interests, Personal, Advisory Board, Advisory boards: Novartis; Financial Interests, Personal, Invited Speaker: Daiichi-Sankyo company limited, MSD, AstraZeneca, Novartis; Financial Interests, Institutional, Research Grant: Beohringer-Ingelheim Japan, MSD, AstraZeneca KK, Ono Pharmaceutical CO.,LTD, Bristol-Myers Squibb KK, Novartis; Financial Interests, Institutional, Invited Speaker: Eli Lilly Japan. All other authors have declared no conflicts of interest.