Nivolumab (ONO-4538/BMS-936558) as salvage treatment after second or later-line chemotherapy for advanced gastric or gastro-esophageal junction cancer (AGC): A double-blinded, randomized, phase III trial.

Cancers of the Esophagus and Stomach
Session Type and Session Title: 
Oral Abstract Session A: Cancers of the Esophagus and Stomach
Poster Session A: Cancers of the Esophagus and Stomach
Abstract Number: 


Poster Board Number: 
Poster Session A Board #D2
J Clin Oncol 35, 2017 (suppl 4S; abstract 2)
Yoon-Koo Kang, Taroh Satoh, Min-Hee Ryu, Yee Chao, Ken Kato, Hyun Cheol Chung, Jen-Shi Chen, Kei Muro, Won Ki Kang, Takaki Yoshikawa, Sang Cheul Oh, Takao Tamura, Keun-Wook Lee, Narikazu Boku, Li-Tzong Chen; Departments of Oncology, Asan Medical Center, University of Ulsan, Seoul, Republic of Korea; Department of Frontier Science for Cancer and Chemotherapy, Osaka University, Graduate School of Medicine, Osaka, Japan; Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea; Department of Oncology, Taipei Veterans General Hospital, Taipei City, Taiwan; Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan; Yonsei Cancer Center, Institute for Cancer Research, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; Chang Gung Memorial Hospital, Taipei, Taiwan; Aichi Cancer Center Hospital, Nagoya, Japan; Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Department of Gastrointestinal Surgery, Kanagawa Cancer Center, Yokohama, Japan; Dvision of Oncology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, South Korea; Kinki University, Osaka, Japan; Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea; National Health Research Institutes (NHRI) - National Institute of Cancer Research, Taipei, Taiwan

Abstract Disclosures


Background: Recent clinical trials have established 1st and 2nd line chemotherapy as the standard treatment for advanced gastric or gastro-esophageal junction cancer (AGC). However, prognosis of AGC is still poor. Nivolumab (ONO-4538/BMS-936558) is a human monoclonal IgG4 antibody which blocks the human programmed cell death-1 (PD-1) receptor. We evaluated the efficacy and safety of nivolumab as salvage treatment after failure of the standard chemotherapy for AGC. Methods: 493 patients aged ≥ 20 years with ECOG PS 0-1 and unresectable advanced or recurrent AGC who had failed two or more previous chemotherapy regimens were randomized in a 2:1 ratio to receive 3 mg/kg nivolumab (N=330) or placebo ( N=163) every 2 weeks until unacceptable toxicity or disease progression. Primary endpoint was overall survival (OS) in Intention-to-Treat population. This trial is registered in ClinicalTrials.gov (NCT02267343). Results: As of the data cut-off on Aug 13th2016, 5.6 months after last patient randomized, median OS was 5.32 months with nivolumab versus 4.14 months with placebo (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.50-0.78; p<0.0001), and OS rates at 6 and 12 month were 46.4% versus 34.7% and 26.6% versus 10.9%, respectively. The overall response rate (ORR) was 11.2% (95% CI, 7.7-15.6) with nivolumab versus 0% (95% CI, 0.0-2.8) with placebo (p<0.0001). Median progression-free survival (PFS) was 1.61 months with nivolumab versus 1.45 months with placebo (HR, 0.60; 95% CI, 0.49-0.75; p<0.0001). Grade ≥ 3 drug-related adverse events (AEs) occurred in 11.5 % of nivolumab and 5.5 % of placebo; 2.7% and 2.5%, respectively, discontinued of study treatment due to drug-related AEs (any grade). Conclusions: Nivolumab was effective as the salvage treatment for pretreated AGC with significantly improved OS, PFS and ORR compared to placebo. Funding:Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb. Clinical trial information: NCT02267343