Randomized, Open‐Label Phase II Study Comparing Capecitabine‐Cisplatin Every 3 Weeks with S‐1‐Cisplatin Every 5 Weeks in Chemotherapy‐Naïve Patients with HER2‐Negative Advanced Gastric Cancer: OGSG1105, HERBIS‐4A Trial

LESSONS LEARNED. Evidence has suggested that capecitabine‐cisplatin is similar or possibly superior to S‐1‐cisplatin in terms of safety and efficacy for Japanese patients with advanced gastric cancer (AGC). As far as we are aware, our study is the first randomized trial of two regimens consisting of an oral fluoropyrimidine plus cisplatin in human epidermal growth receptor 2‐negative AGC patients with measurable lesions. BACKGROUND. We performed a phase II study to evaluate the safety and efficacy of capecitabine plus cisplatin in comparison with S‐1 plus cisplatin for first‐line treatment of human epidermal growth receptor 2 (HER2)‐negative advanced gastric cancer in Japan. METHODS. Eligible patients were randomly assigned to receive either capecitabine at 1,000 mg/m(2) twice daily for 14 days plus cisplatin at 80 mg/m(2) on day 1 every 3 weeks (n = 43) or S‐1 at 40–60 mg twice daily for 21 days plus cisplatin at 60 mg/m(2) on day 8 every 5 weeks (n = 41). The primary endpoint of the study was response rate. RESULTS. Response rate did not differ significantly between the capecitabine‐cisplatin and S‐1‐cisplatin groups (53.5% vs. 51.2%, respectively, p > .999). S‐1‐cisplatin tended to confer a better progression‐free survival (PFS; median of 5.9 vs. 4.1 months, p = .284), overall survival (OS; median of 13.5 vs. 10.0 months, p = .290), and time to treatment failure (TTF; median of 4.5 vs. 3.1 months, p = .052) compared with capecitabine‐cisplatin. Common hematologic toxicities of grade 3 or 4 included anemia and neutropenia in both groups. However, anorexia, fatigue, and hyponatremia of grade 3 or 4 occurred more frequently in the capecitabine‐cisplatin group. CONCLUSION. Capecitabine‐cisplatin failed to demonstrate superior efficacy compared with S‐1‐cisplatin. The higher incidence of severe adverse events with capecitabine‐cisplatin suggests that S‐1‐cisplatin should remain the standard first‐line chemotherapy for HER2‐negative advanced gastric cancer in Japan.