Nivolumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Korean Patients with HER2-Negative, Untreated, Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer: Subgroup Analysis of a Randomized, Multicenter, Double-Blind Phase 3 Trial (ATTRACTION-4).

Abstract

Purpose: We report the safety and efficacy of nivolumab + chemotherapy for first-line treatment of advanced or recurrent gastric or gastroesophageal junction cancer in the Korean subpopulation of the ATTRACTION-4 clinical trial.

Materials and methods: ATTRACTION-4 (NCT02746796) was a double-blind, randomized, placebo-controlled clinical trial of patients aged ≥20 years with histologically confirmed unresectable advanced or recurrent gastric or gastroesophageal junction cancer. Patients received nivolumab or placebo, both combined with physician-choice chemotherapy (oxaliplatin plus oral S-1 [tegafur‒gimeracil‒oteracil] [SOX] or oral capecitabine [CAPOX]).

Results: Overall, 464 patients were initially screened in Korea and 291 were randomized to nivolumab + chemotherapy (total/SOX/CAPOX: 148/66/82 patients) or placebo + chemotherapy (total/SOX/CAPOX: 143/61/82 patients). Centrally assessed progression-free survival (median: 14.75 vs. 8.34 months; hazard ratio [HR] 0.53; 95% confidence interval [CI] 0.39‒0.73, p<0.0001), overall survival (19.7 vs. 14.9 months; HR 0.78; 95% CI 0.60‒1.02, p=0.0651), overall response rate (54.7% vs. 47.6%), and duration of response (16.03 vs. 9.86 months) favored nivolumab + chemotherapy vs. placebo + chemotherapy. Grade ≥3 treatment-related adverse events (TRAEs) (56.1% vs. 44.1%), and any-grade endocrine (9.5% vs. 4.2%), hepatic (23.0% vs. 14.7%), hypersensitivity and infusion reactions (15.5% vs. 7.0%), renal (4.1% vs. 0.7%), and skin (44.6% vs. 23.1%) TRAEs tended to be more frequent in the nivolumab + chemotherapy group.

Conclusion: These findings demonstrate the clinical benefit of nivolumab combined with chemotherapy (either SOX or CAPOX) for first-line treatment of gastric cancer/gastroesophageal junction cancer in Korean patients.