Results of a double-blinded, randomised phase III study, NCT02267343 (lead study investigator Yoon-Koo Kang, MD, PhD, the Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea) presented at 2017 Gastrointestinal Cancers Symposium held in San Francisco, US (19-21 January) indicate that nivolumab as the salvage treatment for pretreated patients with advanced gastric or gastro-oesophageal junction cancer improved outcome compared to placebo.
The investigators explained in the study background that recent clinical trials have established first- and second-line chemotherapy as the standard treatment for advanced gastric or gastro-esophageal junction cancer. However, prognosis of these patients is still poor. They evaluated the efficacy and safety of nivolumab, a human monoclonal IgG4 antibody which blocks the human programmed cell death-1 (PD-1) receptor, as salvage treatment after failure of the standard chemotherapy for advanced gastric or gastro-oesophageal junction cancer.
In their study, the investigators randomised 493 patients aged ≥ 20 years with ECOG performance status 0-1 and unresectable advanced or recurrent advanced gastric or gastro-oesophageal junction cancer who had failed two or more previous chemotherapy regimens 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.
The primary endpoint in the study was overall survival (OS) in intention-to-treat population.
As of the data cut-off on 13 August 2016, 5.6 months after last patient was randomised, median OS was 5.32 months with nivolumab vs 4.14 months with placebo (hazard ratio [HR], 0.63; p<0.0001), and OS rates at 6 and 12 month were 46.4% vs 34.7% and 26.6% vs 10.9%, respectively.
The overall response rate (ORR) was 11.2% with nivolumab vs 0% 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; p<0.0001).
The safety profile of nivolumab was consistent with previously reported studies in solid tumours. Grade ≥ 3 drug-related adverse events (AEs) occurred in 11.5% of nivolumab arm and 5.5% of placebo arm; 2.7% and 2.5% patients, respectively, discontinued of study treatment due to drug-related AEs of any grade.
The investigators concluded that nivolumab was effective as the salvage treatment in pretreated patients with advanced gastric or gastro-oesophageal junction cancer. It is the first randomised, phase III trial in which immunotherapy agent demonstrated improved survival in the setting in which currently there is no standard of care treatment.
The study was funded by Ono Pharmaceutical Co., Ltd. and Bristol-Myers Squibb.
Kang Y-K, Satoh T, Ryu M-R, et al. 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. J Clin Oncol 35, 2017 (suppl 4S; abstract 2)