Safety and efficacy of pembrolizumab in combination with S-1 plus oxaliplatin as a first-line treatment in patients with advanced gastric/gastroesophageal junction cancer: Cohort 1 data from the KEYNOTE-659 phase IIb study

Abstract

Aim: The KEYNOTE-659 study evaluated the efficacy and safety of pembrolizumab in combination with chemotherapy as the first-line treatment in Japanese patients with advanced gastric/gastroesophageal junction (G/GEJ) cancer. In this paper, we report results from cohort 1 (S-1 plus oxaliplatin [SOX] with pembrolizumab).

Methods: This was a non-randomised, multicentre, open-label phase IIb study in patients with advanced programmed death-ligand 1 (PD-L1)-positive, human epidermal growth factor receptor 2-negative G/GEJ tumours. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Exploratory analyses were performed based on the PD-L1 combined positive score (CPS) status.

Results: Fifty-four patients were evaluated. The median follow-up was 10.1 months. ORR and DCR by BICR were 72.2% (95% confidence interval [CI] 58.4-83.5) and 96.3% (95% CI 87.3-99.5), respectively. Median DOR, TTR, PFS and OS were as follows: not reached, 1.5 months, 9.4 months and not reached. The ORR was 73.9% in patients with CPS ≥1 to <10 and 71.0% in those with CPS ≥10. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 57.4% of patients. The most common grade ≥3 TRAEs were decreased platelet count (14.8%), decreased neutrophil count (13.0%), colitis (5.6%) and adrenal insufficiency (5.6%).

Conclusions: SOX with pembrolizumab showed encouraging efficacy and a manageable safety profile for the first-line treatment of advanced G/GEJ cancer.

Trial registration: NCT03382600/JapicCTI-183829.

Keywords: Chemotherapy; Clinical trial; Immunotherapy; Oxaliplatin; Pembrolizumab; Phase II; S-1; Stomach neoplasms.

Conflict of interest statement

Conflict of interest statement Y. Negoro, M. Tsuda, S Shiratori, S.R. Han and T. Oshima, declare no conflicts of interest. A. Kawazoe reports grants and personal fees from Taiho Pharmaceutical and Ono Pharmaceutical and grants from Sumitomo Dainippon Pharma and MSD, outside the submitted work. N. Machida reports personal fees from Taiho Pharmaceutical and MSD, during the conduct of the study. K. Yamaguchi reports grants and personal fees from Taiho, grants from MSD, during the conduct of the study; grants and personal fees from Chugai Pharm, personal fees from Takeda, personal fees from Merck Serono, personal fees from Bayer, grants and personal fees from Daiichi-Sankyo, grants and personal fees from Ono Pharm, grants and personal fees from Lilly Japan, grants from Gilliad, grants from Dainippon Sumitomo, grants from Boehringer Ingelheim, personal fees from Bristol and grants from Sanofi, outside the submitted work. H. Yasui reports personal fees from Taiho Pharmaceutical and Yakult Honsha and grants from MSD, during the conduct of the study; personal fees from Chugai Pharmaceutical, Bristol-Myers Squibb Japan and Eli Lilly Japan; grants and personal fees from Daiichi Sankyo and grants from Ono Pharmaceutical, outside the submitted work. M. Azuma reports grants and personal fees from Taiho Pharmaceutical during the conduct of the study and grants and personal fees from Ono Pharmaceutical, outside the submitted work. K. Amagai reports grants from MSD, during the conduct of the study; grants from MSD, Taiho Pharmaceutical, Bayer, Hisamitsu and Daiichi Sankyo, outside the submitted work. H. Hara reports grants from Japan Agency for Medical Research and Development (AMED) during the conduct of the study; grants from AstraZeneca, Sumitomo Dainippon Pharma, Merck Serono, Eisai, LSK BioPharma, Incyte, Pfizer, Boehringer-Ingelheim and BeiGene; grants and personal fees from Daiichi Sankyo, MSD, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical and BMS and personal fees from Eli Lilly, Yakult Honsha, Sanofi and Takeda Pharmaceutical, outside the submitted work. H. Baba reports grants, personal fees and non-financial support from Taiho Pharmaceutical, during the conduct of the study; grants, personal fees and non-financial support from Ono Pharmaceutical and Eli Lilly Japan; grants and personal fees from Takeda Pharmaceutical and Chugai Pharmaceutical; grants and non-financial support from Merck Serono, Yakult Honsha and Johnson & Johnson and grants from Shionogi & Co, Covidien Japan, Takeda Pharmaceutical, Shin Nippon Biomedical Laboratories, Novartis and Toyama Chemical, outside the submitted work. H. Hosaka reports grants from Taiho Pharmaceutical, Ono Pharmaceutical and Bristol-Myers Squibb, outside the submitted work. H. Kawakami reports personal fees from Bristol-Myers Squibb, Eli Lilly, Taiho Pharmaceutical, Ono Pharmaceutical, Takeda Pharmaceutical, MSD, AstraZeneca, Bayer and Yakult Honsha; grants and personal fees from Chugai Pharmaceutical, Daiichi Sankyo and grants from Eisai, outside the submitted work. Y. Omuro reports grants from MSD, during the conduct of the study and grants from Ono Pharmaceutical, Five Prime, Daiichi Sankyo, Astellas and BeiGene, outside the submitted work. T. Esaki reports grants from Astellas, MSD, Sumitomo Dainippon Pharma, Nihon Kayaku, Novartis and Pfizer; grants and personal fees from Daiichi-Sankyo, Ono Pharmaceutical, Merck Serono, Taiho Pharmaceutical, Eli Lilly, Bayer, Bristol-Myers Squibb; personal fees from Takeda Pharmaceutical, Kyowa Kirin, Chugai Pharmaceutical, Eisai and Sanofi, outside the submitted work. K. Yoshida reports grants and personal fees from Taiho Pharmaceutical and MSD, during the conduct of the study; grants and personal fees from Asahi Kasei Pharma, Chugai Pharmaceutical, Covidien Japan, Daiichi Sankyo, Eisai, Eli Lilly Japan, Johnson & Johnson, Merck Serono, Nippon Kayaku, Novartis, Ono Pharmaceutical, Otsuka Pharmaceutical, Sanofi, Tsumura and Yakult Honsha; grants from Abbott, AbbVie, Astellas, Biogen Japan, Celgene, GlaxoSmithKline, KCI, Kyowa Kirin, Meiji Seika Pharma and Toray Medical and personal fees from AstraZeneca, Bristol-Myers Squibb, Denka, EA Pharma, Olympus, Pfizer, Sanwa Kagaku Kenkyusho, SBI Pharma, Takeda Pharmaceutical, Teijin Pharmaceutical and TERUMO, outside the submitted work. T. Nishina reports grants and personal fees from Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol-Myers Squibb and Eli Lilly and grants from Daiichi Sankyo, MSD and Sumitomo Dainippon Pharma, outside the submitted work. Y. Komatsu reports grants and personal fees from Taiho Pharmaceutical, during the conduct of the study; grants and personal fees from Eli Lilly Japan K.K., Taiho Pharmaceutical, Chugai Pharmaceutical, Takeda Pharmaceutical, Bayer Yakuhin, Ltd., Bristol-Myers Squibb, Sanofi S.A., Merck Biopharma, Ono Pharmaceutical, MSD K.K., Yakult Honsha, Otsuka Pharmaceutical; grants from National Cancer Center Hospital, NanoCarrier, Baxter International Inc., Clinical Co., Ltd., Quintiles and IMS Health, Sysmex Corporation, Mediscience Planning Inc., Sumitomo Dainippon Pharma, Kyowa Kirin, Asahi Kasei Pharma Corporation and Nippon Zoki Pharmaceutical, outside the submitted work. K. Shitara reports grants and personal fees from Astellas Pharma, Eli Lilly, Ono Pharmaceutical and MSD; personal fees from Bristol-Myers Squibb, Takeda Pharmaceutical, Pfizer, Novartis, AbbVie and Yakult Honsha; grants from Sumitomo Dainippon Pharma, Daiichi Sankyo, Taiho Pharmaceutical, Chugai Pharmaceutical and MediScience, outside the submitted work.

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