Perioperative or Postoperative Oxaliplatin/S-1 vs Postoperative Oxaliplatin/Capecitabine for Locally Advanced Gastric Cancer

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In the Chinese phase III RESOLVE trial reported in The Lancet Oncology, Zhang et al found that perioperative S-1/oxaliplatin was superior to—and adjuvant S-1/oxaliplatin was noninferior to—adjuvant capecitabine/oxaliplatin in terms of disease-free survival in patients undergoing D2 gastrectomy for advanced gastric/gastroesophageal junction adenocarcinomas.

Study Details

In the multicenter open-label trial, 1,022 patients (modified intent-to-treat population) with cT4a N+ M0 or cT4b Nany M0 disease who were to undergo gastrectomy were randomly assigned 1:1:1 between August 2012 and February 2017. They either received eight postoperative cycles of capecitabine/oxaliplatin (n = 345), eight postoperative cycles of S-1/oxaliplatin (n = 340), or three preoperative cycles and five postoperative cycles of S-1/oxaliplatin followed by three cycles of S-1 monotherapy (n = 337). The primary endpoint was 3-year disease-free survival in the modified intent-to-treat population, with testing of superiority (significance level = .05) for perioperative S-1/oxaliplatin and noninferiority (noninferiority threshold hazard ratio = 1.33) of adjuvant S-1/oxaliplatin vs adjuvant capecitabine/oxaliplatin.

Disease-Free Survival

At database lock (May 2020), median follow-up was 40.6 months (interquartile range = 18.2–53.1 months). Disease-free survival at 3 years was 51.1% (95% confidence interval [CI] = 45.5%–56.3%) in the adjuvant capecitabine/oxaliplatin group, 56.5% (95% CI = 51.0%–61.7%) in the adjuvant S-1/oxaliplatin group, and 59.4% (95% CI = 53.8%–64.6%) in the perioperative S-1/oxaliplatin group; hazard ratios were 0.77 (95% CI = 0.61–0.97, P = .028) for perioperative S-1/oxaliplatin vs adjuvant capecitabine/oxaliplatin and 0.86 (95% CI = 0.68–1.07, P = .17) for adjuvant S-1/oxaliplatin vs adjuvant capecitabine/oxaliplatin.


  • Perioperative oxaliplatin/S1 was associated with superior disease-free survival vs adjuvant capecitabine/oxaliplatin.
  • Adjuvant oxaliplatin/S1 was noninferior to adjuvant capecitabine/oxaliplatin.

Overall survival data were not mature at time of analysis. R0 resection rates were 87% in the adjuvant capecitabine/oxaliplatin group, 88% in the adjuvant S-1/oxaliplatin group, and 93% in the perioperative S-1/oxaliplatin group. Among 117 evaluable patients in the perioperative S-1/oxaliplatin group, the objective response rate to preoperative treatment was 41.0%.

Adverse Events

Grade ≥ 3 adverse events occurred in 17% of patients in the adjuvant capecitabine/oxaliplatin group, 19% of the adjuvant S-1/oxaliplatin group, and 21% of the perioperative S-1/oxaliplatin group, with most common being neutropenia (12%, 8%, and 10%, respectively). Rates of grade 3 or 4 thrombocytopenia (P = .013) and anemia (P = .0048) were higher in the perioperative S-1/oxaliplatin group vs the adjuvant capecitabine/oxaliplatin group. No other significant differences in grade 3 or 4 events were observed between groups. Serious adverse events occurred in 3%, 3%, and 2% of patients, respectively. No treatment-related deaths were reported.

The investigators concluded, “Perioperative S-1/oxaliplatin showed a clinically meaningful improvement compared with adjuvant capecitabine/oxaliplatin in patients with locally advanced gastric cancer who had D2 gastrectomy; adjuvant S-1/oxaliplatin was noninferior to adjuvant capecitabine/oxaliplatin in these patients. Perioperative S-1/oxaliplatin could be considered a new treatment option for patients with locally advanced gastric cancer.”

Jiafu Ji, MD, of the Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the National Key Research and Development Program of China, Peking University Clinical Scientist Program, Taiho, Sanofi-Aventis, Hengrui Pharmaceutical, and others. For full disclosures of the study authors, visit

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