Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): final report of a randomised, open-label, phase 3 trial
Mené sur 1 094 patients atteints d'un adénocarcinome de l'estomac ou de la jonction oesogastrique (durée médiane de suivi : 62,8 mois), cet essai randomisé de phase III évalue l'efficacité, du point de vue de la survie globale à 5 ans, de S-1 en combinaison avec l'oxaliplatine (SOX) en traitement périopératoire et postopératoire par rapport à un traitement postopératoire par capécitabine-oxaliplatine (CapOx)
Background: The multicentre RESOLVE trial examined the efficacy of perioperative and postoperative S-1 and oxaliplatin (SOX) compared with postoperative capecitabine and oxaliplatin (CapOx) in gastric or gastro-oesophageal junction cancer. Initial analyses did not encompass overall survival owing to the immature data. This paper provides an updated analysis of the survival data from the RESOLVE trial.
Methods: In this randomised, open-label, phase 3 study, participants aged 18 years or older with cT4a N+ M0 or cT4b Nany M0 gastric or gastro-oesophageal junction adenocarcinoma who were feasible for D2 lymphadenectomy and had a Karnofsky performance score of 70 or higher were enrolled. Participants were randomly assigned in a 1:1:1 ratio via an interactive web response system, stratified by participating centres and Lauren classification, to receive adjuvant CapOx (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral capecitabine 1000 mg/m2 twice a day on days 1–14, adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral S-1 40–60 mg twice a day on days 1–14), or perioperative SOX (intravenous oxaliplatin 130 mg/m2 on day 1 of each 21-day cycle plus oral S-1 40–60 mg twice a day for three cycles preoperatively and five cycles postoperatively followed by three cycles of S-1 monotherapy. The primary endpoint, assessed in the modified intention-to-treat population, was 3-year disease-free survival to assess the superiority of perioperative-SOX compared with adjuvant-CapOx and the non-inferiority (hazard ratio [HR] non-inferiority margin of 1·33) of adjuvant-SOX compared with adjuvant-CapOx, and has been reported previously. This final report focuses on the secondary endpoint of 5-year overall survival, also assessed in the modified intention-to-treat population. Other secondary endpoints—R0 resection rate and safety—were not updated in this analysis. The study is registered at ClinicalTrials.gov, NCT01534546, and is complete.
Findings: Between Aug 15, 2012, and Feb 28, 2017, 1094 patients were enrolled and randomly assigned, of whom 1022 participants were included in the modified intention-to-treat population: 345 (259 male, 86 female) in the adjuvant-CapOx group, 340 (238 male, 102 female) in the adjuvant-SOX group, and 337 (271 male, 66 female) in the perioperative-SOX group. As of April 7, 2022, the median duration of follow-up was 62·8 months (IQR 52·0–75·1). The 5-year overall survival rates were 52·1% (95% CI 46·3–57·5) for the adjuvant-CapOx group, 61·0% (55·3–66·2) for the adjuvant-SOX group, and 60·0% (54·2–65·3), for the perioperative-SOX group. Overall survival was significantly prolonged with perioperative-SOX (HR 0·79; 95% CI 0·62–1·00, p=0·049) and adjuvant-SOX (HR 0·77, 0·61–0·98, p=0·033), compared with adjuvant-CapOx.
Interpretation: 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 gastro-oesophageal junction cancer management in Asian patients.
The Lancet Oncology 2024