Zhang Xiaotian, Liang Han, Li Ziyu, Xue Yingwei, Wang Yanong, Zhou Zhiwei, Yu Jiren, Bu Zhaode, Chen Lin, Du Yian, Wang Xinbao, Wu Aiwen, Li Guoli, Su Xiangqian, Xiao Gang, Cui Ming, Wu Dan, Chen Li, Wu Xiaojiang, Zhou Yanbing, Zhang Lianhai, Dang Chengxue, He Yulong, Zhang Zhongtao, Sun Yihong, Li Yong, Chen Huanqiu, Bai Yuxian, Wang Yakun, Yu Peiwu, Zhu Guanbao, Suo Jian, Jia Baoqing, Li Leping, Huang Changming, Li Fei, Ye Yingjiang, Xu Huimian, Wang Xin, Yuan Yannan, E Jianyu, Ying Xiangji, Yao Chen, Shen Lin, Ji Jiafu
State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China.
Department of Abdominal Oncology Surgery, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China.
Lancet Oncol. 2025 Mar;26(3):312-319. doi: 10.1016/S1470-2045(24)00676-4. Epub 2025 Feb 11.
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.
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/m on day 1 of each 21-day cycle plus oral capecitabine 1000 mg/m twice a day on days 1-14, adjuvant SOX (eight postoperative cycles of intravenous oxaliplatin 130 mg/m 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/m 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.
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.
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 National Key Research and Development Program of China, the National Natural Science Foundation of China, the Capital's Funds for Health Improvement and Research, the Beijing Natural Science Foundation, National Natural Science Foundation of China, the Beijing Natural Science Foundation, Taiho, Hengrui Pharmaceutical and Sanofi-Aventis.
For the Chinese translation of the abstract see Supplementary Materials section.
多中心RESOLVE试验比较了围手术期和术后使用S-1与奥沙利铂（SOX）方案和术后使用卡培他滨与奥沙利铂（CapOx）方案治疗胃或胃食管交界癌的疗效。由于数据不成熟，初始分析未纳入总生存期。本文提供了RESOLVE试验生存数据的更新分析。
在这项随机、开放标签的3期研究中，纳入年龄在18岁及以上、患有cT4a N+ M0或cT4b Nany M0胃或胃食管交界腺癌、可行D2淋巴结清扫且卡氏功能状态评分在70分及以上的患者。通过交互式网络响应系统，按照1:1:1的比例将参与者随机分配，根据参与中心和劳伦分类进行分层，分别接受辅助CapOx方案（每21天周期的第1天静脉注射奥沙利铂130 mg/m²，同时在第1 - 14天口服卡培他滨1000 mg/m²，每日2次，共8个术后周期）、辅助SOX方案（每21天周期的第1天静脉注射奥沙利铂130 mg/m²，同时在第1 - 14天口服S-1 40 - 60 mg，每日2次，共8个术后周期）或围手术期SOX方案（每21天周期的第1天静脉注射奥沙利铂130 mg/m²，同时在术前3个周期和术后5个周期口服S-1 40 - 60 mg，每日2次，随后进行3个周期的S-1单药治疗）。在意向性分析人群中评估的主要终点是3年无病生存期，以评估围手术期SOX方案相对于辅助CapOx方案的优越性以及辅助SOX方案相对于辅助CapOx方案的非劣效性（风险比[HR]非劣效界值为1.33），此前已有报道。本最终报告关注的是5年总生存期这一二级终点，同样在意向性分析人群中进行评估。其他二级终点——R0切除率和安全性——在本次分析中未更新。该研究已在ClinicalTrials.gov注册，注册号为NCT01534546，且已完成。
在2012年8月15日至2017年2月28日期间，共纳入1094例患者并随机分配，其中1022例参与者被纳入意向性分析人群：辅助CapOx组345例（男性259例，女性86例），辅助SOX组340例（男性238例，女性102例），围手术期SOX组337例（男性271例，女性66例）。截至2022年4月7日，中位随访时间为62.8个月（IQR 52.0 - 75.1）。辅助CapOx组的5年总生存率为52.1%（95%CI 46.3 - 57.5），辅助SOX组为61.0%（55.3 - 66.2），围手术期SOX组为60.0%（54.2 - 65.3）。与辅助CapOx方案相比，围手术期SOX方案（HR 0.79；95%CI 0.62 - 1.00，p = 0.049）和辅助SOX方案（HR 0.77，0.61 - 0.98，p = 0.033）显著延长了总生存期。
与3年无病生存期的初始分析一致，RESOLVE试验的5年总生存期延长分析证实，与标准辅助CapOx方案相比，围手术期SOX方案和辅助SOX方案具有生存优势。对于亚洲患者局部晚期胃或胃食管交界癌的治疗，围手术期或辅助使用SOX方案有望成为潜在的标准治疗模式。
中国国家重点研发计划、中国国家自然科学基金、首都健康改善与研究基金、北京市自然科学基金、中国国家自然科学基金、北京市自然科学基金、大鹏药业、恒瑞医药和赛诺菲 - 安万特。
中文翻译摘要见补充材料部分。
