美国陶西格癌症研究学院Brian I Rini课题组，研究了阿特唑利单抗联合贝伐单抗与舒尼替尼在以前未经治疗的转移性肾细胞癌患者中的应用(IMmotion151)。相关论文于2019年6月发表于国际顶尖学术期刊《柳叶刀》杂志上。

据介绍，一项二期试验显示，在表达程序性死亡配体1 (PD-L1)的转移性肾细胞癌患者中，阿特唑利单抗加贝伐单抗与舒尼替尼相比，可改善无进展生存期。

研究组报告了IMmotion151的结果，这是一项三期试验，比较阿特唑利单抗加贝伐单抗与舒尼替尼在一线转移性肾细胞癌中的疗效。在这项多中心、开放标签、第3期、随机对照试验中，来自21个国家152个学术医疗中心和社区肿瘤实践中心的患者(主要分布在欧洲、北美和亚太地区)，其中包括透明细胞或肉瘤样组织学成分的患者，他们之前没有接受过治疗。随机分配阿特佐利单抗1200 mg +贝伐单抗15 mg/kg，静脉注射，每3周一次;舒尼替尼50 mg，口服，连续4周，间断2周。采用渗透区随机化(区大小为4)，根据分层因素对每个治疗组进行均衡分配。研究人员和参与者对治疗分配没有隐瞒。联合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)人群的总体生存期。

在2015年5月20日至2016年10月12日登记的915例患者中，454例随机分配给阿特唑利单抗加贝伐单抗组，461例随机分配给舒尼替尼组。 915例患者中有362例(40%)PD-L1阳性。随访中位数为15个月的原发性无进展生存分析和24个月的总体生存中期分析。 PD-L1阳性人群中，atezolizumab +贝伐单抗组无进展生存中值为11·2个月，而舒尼替尼组为7·7个月(危险比[HR] 0·74 [95% CI 0·57-0·96];p = 0·0217)。 在ITT人群中，中位总生存时间为0·93(0·76-1·14)，在中期分析中，结果没有越过显著性边界。182(40%)的atezolizumab加贝伐单抗组的451名患者和240年(54%)舒尼替组的446名患者治疗相关的3 - 4级不良事件:24 atezolizumab加贝伐单抗组(5%)和舒尼替组37例(8%)治疗相关的各年级的不良事件,导致治疗方案停止。与舒尼替尼相比，阿特唑利单抗加贝伐单抗延长了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。 长期随访是必要的，以确定是否会出现生存益处。 这些研究结果支持阿特唑利单抗联合贝伐单抗作为选择的晚期肾细胞癌患者的一线治疗方案。

附：英文原文

Title: Atezolizumab plus bevacizumab versus sunitinib in patients with previously untreated metastatic renal cell carcinoma (IMmotion151): a multicentre, open-label, phase 3, randomised controlled trial

Author: Brian I Rini.Thomas Powles, Michael B Atkins, Bernard Escudier, David F McDermott, Cristina Suarez, Sergio Bracarda, Walter M Stadler, Frede Donskov,Jae Lyun Lee,Robert Hawkins, Alain Ravaud, Boris Alekseev, Michael Staehler, Motohide Uemura, Ugo De Giorgi, Begoña Mellado,Camillo Porta, Bohuslav Melichar, Howard Gurney, Jens Bedke, Toni K Choueiri, Francis Parnis, Tarik Khaznadar, Alpa Thobhani, Shi Li,Elisabeth Piault-Louis,Gretchen Frantz, Mahrukh Huseni, Christina Schiff, Marjorie C Green, Robert J Motzer

Issue&Volume: Volume 393,Number 10189,2019

Abstract:

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.

DOI: https://doi.org/10.1016/S0140-6736(19)30723-8

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)30723-8/fulltext#