S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin as first-line therapy in patients with advanced gastric cancer (SOLAR): a randomised, open-label, phase 3 trial
S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin as first-line therapy in patients with advanced gastric cancer (SOLAR): a randomised, open-label, phase 3 trial
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DOI：
10.1016/s1470-2045(20)30315-6
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发表时间：
2020-08-01
期刊：
影响因子：
51.1
通讯作者：
Boku, Narikazu
中科院分区：
文献类型：
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作者：
Kang, Yoon-Koo;Chin, Keisho;Boku, Narikazu
背景：在一项随机的2期研究中，S-1联合亚叶酸钙和奥沙利铂治疗进展期胃癌显示出良好的疗效。我们旨在评价口服TAS-118(S-1联合亚叶酸钙)和奥沙利铂与S-1联合顺铂治疗晚期胃癌的疗效和安全性。方法我们在日本和韩国的62个中心进行了随机、开放的3期试验。20岁或20岁以上、组织学确诊的HER2阴性或未知的进展期胃癌、东方合作肿瘤组功能状态为0或1、可测量或可评估的转移病变、以及以前没有治疗的患者被随机分配(1：1)，通过使用最小化方法的交互式网络响应系统，按性能状态、是否存在可测量的病变和国家进行分层，接受TAS-118(S-140-60 mg和亚叶酸钙25 mg，每日两次口服，连续7天)加奥沙利铂(85 mg/m(2)，第1天静脉注射)，每2周，或S-1(40~60 mg，每日2次)口服，疗程21d，加顺铂(60 mg/m(2)，第1天或第8天静脉滴注)，每5周1次。主要终点是患有可测量或可评估转移灶的进展期胃癌并接受研究药物治疗的患者的总存活率。对所有接受研究药物的患者进行了安全性评估。在2015年1月28日至2016年12月5日期间，711名患者被随机分为TAS-118联合奥沙利铂组(n=356)或S-1联合顺铂组(n=355)。根据独立数据监测委员会的建议，11例初治患者和19例不合格患者被排除在初步分析之外(TAS-118+奥沙利铂组347例，S-1+顺铂组334例)。中位随访期26个月(IQR22.0~32.8)，TAS-118联合奥沙利铂组和S-1联合顺铂组的中位总生存期分别为16.0个月(95%CI 13.8~18.3)和15.1个月(95%CI 13.6~16.4)(风险比0.83，95%CI 0.69~0.99；P=0.039)。在TAS-118联合奥沙利铂组和S-1联合顺铂组的348例患者中，最常见的3级或更高的不良事件是贫血(56[16%]比[18%])、中性粒细胞减少(54[15%]比88[25%])、食欲下降(53[15%]比46[13%])、腹泻(33[9%]比15[4%])和周围感觉神经病变(30[9%]比1
Background S-1 plus leucovorin and oxaliplatin showed promising efficacy for treatment of advanced gastric cancer in a randomised phase 2 study. We aimed to evaluate the efficacy and safety of oral TAS-118 (S-1 plus leucovorin) and oxaliplatin versus S-1 plus cisplatin in patients with advanced gastric cancer.Methods We did a randomised, open-label, phase 3 trial in 62 centres across Japan and South Korea. Patients aged 20 years or older, with a histologically confirmed advanced gastric cancer with negative or unknown HER2 status, with Eastern Cooperative Oncology Group performance status of 0 or 1, measurable or evaluable metastatic lesions, and no previous treatment were randomly assigned (1:1) via an interactive web response system using the minimisation method, stratified by performance status, presence of a measurable lesion, and country, to receive TAS-118 (S-140-60 mg and leucovorin 25 mg orally twice daily for 7 days) plus oxaliplatin (85 mg/m(2) intravenously on day 1) every 2 weeks, or S-1 (40-60 mg orally twice daily) for 21 days plus cisplatin (60 mg/m(2) intravenously on day 1 or 8) every 5 weeks. The primary endpoint was overall survival in patients who had advanced gastric cancer with measurable or evaluable metastatic lesions and who received the study drug. Safety was assessed in all patients who received the study drug. This study was registered at ClinicalTrials.gov, NCT02322593.Findings Between Jan 28,2015, and Dec 5,2016,711 patients were randomised to TAS-118 plus oxaliplatin (n=356) or S-1 plus cisplatin (n=355). 11 untreated patients and 19 ineligible patients were excluded from the primary analysis (TAS-118 plus oxaliplatin group n=347, S-1 plus cisplatin group n=334) following recommendation from the independent data monitoring committee. After median follow-up of 26.0 months (IQR 22.0-32.8), median overall survival was 16.0 months (95% CI 13.8-18.3) in the TAS-118 plus oxaliplatin group and 15.1 months (95% CI 13.6-16.4) in the S-1 plus cisplatin group (hazard ratio 0.83, 95% CI 0.69-0.99; p=0.039). The most common grade 3 or higher adverse events in the 352 patients in the TAS-118 plus oxaliplatin group and the 348 patients in the S-1 plus cisplatin group were anaemia (56 [16%] vs 64 [18%]), neutropenia (54 [15%] vs 88 [25%]), decreased appetite (53 [15%] vs 46 [13%]), diarrhoea (33 [9%] vs 15 [4%]), and peripheral sensory neuropathy (30 [9%] vs one [