Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial
Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): a randomised, double-blind, placebo-controlled, phase 3 trial
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DOI：
10.1016/s0140-6736(16)32453-9
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发表时间：
2017-01-07
期刊：
影响因子：
168.9
通讯作者：
Han, Guohong
中科院分区：
文献类型：
--
作者：
Bruix, Jordi;Qin, Shukui;Han, Guohong
背景没有针对肝细胞癌（HCC）患者的全身治疗，其疾病在索拉非尼治疗期间进展。我们旨在评估雷莫非尼在索拉非尼治疗期间进展的HCC患者的疗效和安全性。在这种随机的，双盲的，平行组的方法中，在21个国家 /地区的152个地点进行了3阶段试验，患有HCC的成年人，他们容忍了HCC索拉非尼（> = 400 mg/day> = =最后28天的治疗中的20个），在索拉非尼上进行，并具有儿童肝功能是注册。参与者由计算机生成的随机化列表和互动语音响应系统随机分配（2：1），并按地理区域，东部合作肿瘤学组绩效状态，大血管侵袭，肝外疾病和A-胜利蛋白水平进行分层，以最好在每个4周周期的1-3周中，口服重伐尼160毫克或安慰剂每天一次。调查人员，患者和资助者被掩盖到治疗分配中。主要终点是总生存期（定义为从随机化到死亡的时间），并通过治疗意图进行分析。该试验已在ClinicalTrials.gov中注册，数字NCT01774344。筛查2013年5月14日至2015年12月31日之间的调查，筛查了843例患者，其中573例被录入并随机分配（379例（379）（379）与Regorafenib和194例安慰剂；人口进行效率分析； ）和567次开始治疗（374次接受了雷伐尼，193次接受安慰剂；为了安全性人口分析）。雷莫非尼提高了总体生存率，危险比为0.63（95％CI 0.50-0.79；单侧P
Background There are no systemic treatments for patients with hepatocellular carcinoma (HCC) whose disease progresses during sorafenib treatment. We aimed to assess the efficacy and safety of regorafenib in patients with HCC who have progressed during sorafenib treatment.Methods In this randomised, double-blind, parallel-group, phase 3 trial done at 152 sites in 21 countries, adults with HCC who tolerated sorafenib (>= 400 mg/day for >= 20 of last 28 days of treatment), progressed on sorafenib, and had Child-Pugh A liver function were enrolled. Participants were randomly assigned (2: 1) by a computer-generated randomisation list and interactive voice response system and stratified by geographical region, Eastern Cooperative Oncology Group performance status, macrovascular invasion, extrahepatic disease, and a-fetoprotein level to best supportive care plus oral regorafenib 160 mg or placebo once daily during weeks 1-3 of each 4-week cycle. Investigators, patients, and the funder were masked to treatment assignment. The primary endpoint was overall survival (defined as time from randomisation to death due to any cause) and analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01774344.Findings Between May 14, 2013, and Dec 31, 2015, 843 patients were screened, of whom 573 were enrolled and randomised (379 to regorafenib and 194 to placebo; population for efficacy analyses), and 567 initiated treatment (374 received regorafenib and 193 received placebo; population for safety analyses). Regorafenib improved overall survival with a hazard ratio of 0.63 (95% CI 0.50-0.79; one-sided p