As reported in The Lancet Oncology by Zhang et al, final outcomes of the Chinese phase III RESOLVE trial showed improved overall survival with adjuvant S-1 and oxaliplatin (SOX) and perioperative SOX vs adjuvant capecitabine/oxaliplatin (CapOx) in patients with locally advanced gastric or gastroesophageal junction adenocarcinoma undergoing D2 gastrectomy.
Study Details
In the multicenter, open-label study, 1,022 patients (modified intention-to treat population) were randomly assigned 1:1:1 between August 2012 and February 2017 to receive eight cycles of adjuvant CapOx (n = 345), eight cycles of adjuvant SOX (n = 340), or three preoperative cycles and five postoperative cycles of SOX followed by three cycles of S-1 monotherapy (n = 337). Initial findings showed a significant improvement in the primary endpoint of 3-year disease-free survival for the perioperative SOX group vs the adjuvant CapOx group (59.4% vs 51.1%, hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.61–0.97). The final report provides 5-year overall survival and 5-year disease-free survival analyses.
Key Findings
Median duration of follow-up was 62.8 months (interquartile range = 52.0–75.1 months). Overall survival rate at 5 years was 52.1% (95% CI = 46.3%–57.5%) in the adjuvant CapOx group, 61.0% (95% CI = 55.3%–66.2%) in the adjuvant SOX group, and 60.0% (95% CI = 54.2%–65.3%) in the perioperative SOX group. Compared with the adjuvant CapOx group, overall survival was significantly better with perioperative SOX (HR = 0.79, 95% CI = 0.62–1.00, P = .049) and adjuvant SOX (HR = 0.77, 95% CI = 0.61–0.98, P = .033).
At 5 years, disease-free survival rate was 45.8% (95% CI = 40.2%–51.2%) in the adjuvant CapOx group, 50.8% (95% CI = 45.2%–56.2%) in the adjuvant SOX group, and 53.2% (95% CI = 47.4%–58.6%) in the perioperative SOX group. Compared with the adjuvant CapOx group, disease-free survival was significantly improved in the perioperative SOX group (HR = 0.79, 95% CI = 0.63–0.98) and noninferior in the adjuvant SOX group (HR = 0.86, 95% CI = 0.69–1.06, below the noninferiority threshold of HR < 1.33).
The investigators concluded: “Consistent with the initial analysis of 3-year disease-free survival, the extended 5-year overall survival analysis from the RESOLVE trial confirmed the survival advantage of perioperative SOX and adjuvant SOX compared with the standard adjuvant CapOx regimen. The SOX regimen, given perioperatively or as an adjuvant treatment, emerges as a potential standard treatment modality for locally advanced gastric or gastroesophageal junction cancer management in Asian patients.”
Jiafu Ji, MD, of the Gastrointestinal Cancer Center, and Lin Shen, MD, of the Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, are the corresponding authors of The Lancet Oncology article.
Disclosure: The study was funded by the National Key Research and Development Program of China, National Natural Science Foundation of China, Taiho, Hengrui Pharmaceutical, Sanofi-Aventis, and others. For full disclosures of the study authors, visit thelancet.com.
