Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial
Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial
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DOI：
10.1016/s0140-6736(19)30723-8
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发表时间：
2019-06-15
期刊：
影响因子：
168.9
通讯作者：
Motzer, Robert J.
中科院分区：
文献类型：
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作者：
Rini, Brian I.;Powles, Thomas;Motzer, Robert J.
一项2期试验显示，在表达程序性死亡配体1 （PD-L1）的转移性肾癌患者中，atezolizumab联合贝伐单抗与舒尼替尼相比可改善无进展生存期。在这里，我们报告了IMmotion151的结果，这是一项比较阿特唑单抗加贝伐单抗与舒尼替尼治疗一线转移性肾细胞癌的3期试验。在这项多中心、开放标签、3期随机对照试验中，从21个国家（主要在欧洲、北美和亚太地区）的152个学术医疗中心和社区肿瘤学实践中招募了具有透明细胞或肉瘤样组织学成分且先前未接受治疗的患者。并被随机按1:1分配到阿特唑单抗1200毫克加贝伐单抗15毫克/公斤静脉注射，每3周一次，或舒尼替尼50毫克口服，每天一次，持续4周，休息2周。采用排列块随机化（块大小为4），根据分层因素对每个治疗组进行平衡分配。研究调查人员和参与者不受治疗分配的影响。患者、研究人员、独立放射学委员会成员和申办者都不知道PD-L1的表达状态。共同主要终点是研究人员评估的PD-L1阳性人群的无进展生存期和意向治疗（ITT）人群的总生存期。该试验已在ClinicalTrials.gov注册，编号NCT02420821。在2015年5月20日至2016年10月12日期间入组的915名患者中，454名被随机分配到阿特唑单抗+贝伐单抗组，461名被随机分配到舒尼替尼组。915例患者中有362例（40%）为PD-L1阳性。初始无进展生存期分析的中位随访时间为15个月，总生存期中期分析的中位随访时间为24个月。在PD-L1阳性人群中，阿特唑单抗联合贝伐单抗组的中位无进展生存期为11.2个月，而舒尼替尼组为7.7个月（风险比[HR] 0.74 [95% CI 0.57-0.96]; p=0.0217）。在ITT人群中，中位总生存率的HR为0.93(0.76-1.14)，中期分析结果未跨越显著性边界。阿特唑单抗加贝伐单抗组451例患者中有182例（40%）和舒尼替尼组446例患者中有240例（54%）发生与治疗相关的3-4级不良事件：阿特唑单抗加贝伐单抗组24例（5%）和舒尼替尼组37例（8%）发生与治疗相关的全级不良事件，导致治疗方案停止。与舒尼替尼相比，Atezolizumab联合贝伐珠单抗延长转移性肾细胞癌患者的无进展生存期，并显示出良好的安全性。有必要进行长期随访，以确定是否会出现生存获益。这些研究结果支持atezolizumab联合贝伐单抗作为晚期肾细胞癌患者的一线治疗选择。Elsevier Ltd.版权所有版权所有。
Background A phase 2 trial showed improved progression-free survival for atezolizumab plus bevacizumab versus sunitinib in patients with metastatic renal cell carcinoma who express programmed death-ligand 1 (PD-L1). Here, we report results of IMmotion151, a phase 3 trial comparing atezolizumab plus bevacizumab versus sunitinib in first-line metastatic renal cell carcinoma.Methods In this multicentre, open-label, phase 3, randomised controlled trial, patients with a component of clear cell or sarcomatoid histology and who were previously untreated, were recruited from 152 academic medical centres and community oncology practices in 21 countries, mainly in Europe, North America, and the Asia-Pacific region, and were randomly assigned 1:1 to either atezolizumab 1200 mg plus bevacizumab 15 mg/kg intravenously once every 3 weeks or sunitinib 50 mg orally once daily for 4 weeks on, 2 weeks off. A permuted-block randomisation ( block size of 4) was applied to obtain a balanced assignment to each treatment group with respect to the stratification factors. Study investigators and participants were not masked to treatment allocation. Patients, investigators, independent radiology committee members, and the sponsor were masked to PD-L1 expression status. Co-primary endpoints were investigator-assessed progression-free survival in the PD-L1 positive population and overall survival in the intention-to-treat (ITT) population. This trial is registered with ClinicalTrials.gov, number NCT02420821.Findings Of 915 patients enrolled between May 20, 2015, and Oct 12, 2016, 454 were randomly assigned to the atezolizumab plus bevacizumab group and 461 to the sunitinib group. 362 (40%) of 915 patients had PD-L1 positive disease. Median follow-up was 15 months at the primary progression-free survival analysis and 24 months at the overall survival interim analysis. In the PD-L1 positive population, the median progression-free survival was 11.2 months in the atezolizumab plus bevacizumab group versus 7.7 months in the sunitinib group (hazard ratio [HR] 0.74 [95% CI 0.57-0.96]; p=0.0217). In the ITT population, median overall survival had an HR of 0.93 (0.76-1.14) and the results did not cross the significance boundary at the interim analysis. 182 (40%) of 451 patients in the atezolizumab plus bevacizumab group and 240 (54%) of 446 patients in the sunitinib group had treatment-related grade 3-4 adverse events: 24 (5%) in the atezolizumab plus bevacizumab group and 37 (8%) in the sunitinib group had treatment-related all-grade adverse events, which led to treatment-regimen discontinuation.Interpretation Atezolizumab plus bevacizumab prolonged progression-free survival versus sunitinib in patients with metastatic renal cell carcinoma and showed a favourable safety profile. Longer-term follow-up is necessary to establish whether a survival benefit will emerge. These study results support atezolizumab plus bevacizumab as a first-line treatment option for selected patients with advanced renal cell carcinoma. Copyright (C) 2019 Elsevier Ltd. All rights reserved.