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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

Yoon-Koo Kang, Taroh Satoh, Min-Hee Ryu, Yee Chao, Ken Kato, Hyun Cheol Chung, et al.

.J Clin Oncol 35, 2017 (suppl 4S; abstract 2)

Editorial comment from Prof. Florian Lordick: 
This is the first study that proofs the efficacy of immune checkpoint inhibition in the situation of chemotherapy refractory advanced gastric cancer. It isimportant that part of the patients achieved long duration of response or long duration of stabledisease, which contributes to the overall positive survival results with a considerable number of patientsin the investigational arm who survive for 12 months or longer. It will be important to define biomarkersand other predictors for benefit and longterm survival in order to select the right patients for immunecheckpoint blockade. ONO-4583 did not report such analyses thus far. In addition, we are waiting forresults from studies that investigate immune checkpoint inhibitors in earlier lines of treatment, incombination with chemotherapy and biologics and in the adjuvant setting.



Recent clinical trials have established 1st and 2nd line chemotherapy as thestandard 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 monoclonalIgG4 antibody which blocks the human programmed cell death-1 (PD-1) receptor. We evaluatedthe efficacy and safety of nivolumab as salvage treatment after failure of the standardchemotherapy for AGC


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 (NCT02267343).


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).


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

All content © 2017 American Society of Clinical Oncology. All rights reserved.

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