Multicenter phase III trial of S-1 and cisplatin versus S-1 and oxaliplatin combination chemotherapy for first-line treatment of advanced gastric cancer (SOPP trial).

BACKGROUND In East Asia, S-1 plus cisplatin (SP) is one of the standard first-line chemotherapy regimens for metastatic or recurrent gastric cancer (MRGC). Oxaliplatin is generally less toxic and more convenient to administer than cisplatin. PATIENTS AND METHODS This was a multicenter, phase III study assessing whether S-1/oxaliplatin (SOX) was non-inferior/superior to SP in terms of progression-free survival (PFS). Patients with MRGC were randomized 1:1 to receive either SOX (S-1 80 mg/m2/day on days 1-14; oxaliplatin 130 mg/m2 on day 1; every 3 weeks) or SP (S-1 80 mg/m2/day on days 1-14; cisplatin 60 mg/m2 on day 1; every 3 weeks [SP3]). RESULTS Between October 2012 and October 2014, 338 patients were randomized. The median age was 56 years, and 51% of patients had measurable lesions. SOX was significantly non-inferior but not superior to SP3 in terms of PFS [median 5.6 versus 5.7 months; hazard ratio (HR) 0.85; 95% confidence interval (CI) 0.67-1.07]. In patients with measurable disease, objective response rates were similar between SOX and SP3 (58% versus 60%). Overall, the survival in both groups did not differ (median 12.9 versus 11.4 months; HR 0.86; 95% CI 0.66-1.11). Treatment was well tolerated in both arms. Anemia, leucopenia, neutropenia, febrile neutropenia, and oral mucositis were more common with SP3. In contrast, thrombocytopenia, nausea, vomiting, and peripheral neuropathy were more common with SOX. CONCLUSIONS SOX was non-inferior to SP3. The two regimens were well tolerated with different toxicity profiles. The SOX regimen can be recommended as a first-line treatment for MRGC. TRIAL REGISTRATION ClinicalTrials.gov: NCT01671449.