Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
Barts Cancer Institute and the Royal Free Hospital, Queen Mary University of London, London, UK.
Lancet. 2019 Jun 15;393(10189):2404-2415. doi: 10.1016/S0140-6736(19)30723-8. Epub 2019 May 9.
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.
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.
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.
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.
F Hoffmann-La Roche Ltd and Genentech Inc.
一项 2 期临床试验显示，与舒尼替尼相比，在表达程序性死亡配体 1（PD-L1）的转移性肾细胞癌患者中，阿替利珠单抗联合贝伐珠单抗可改善无进展生存期。在此，我们报告了 IMmotion151 的结果，这是一项 3 期临床试验，比较了阿替利珠单抗联合贝伐珠单抗与舒尼替尼作为转移性肾细胞癌的一线治疗。
在这项多中心、开放标签、3 期、随机对照试验中，招募了来自 21 个国家的 152 个学术医疗中心和社区肿瘤学实践中心的患者，这些患者有明确细胞或肉瘤样组织学成分，且为未经治疗的患者。这些患者被随机分配为 1:1 组，分别接受阿替利珠单抗 1200mg 加贝伐珠单抗 15mg/kg 静脉输注，每 3 周一次，或舒尼替尼 50mg 口服，每日一次，连用 4 周，停药 2 周。采用置换块随机化（块大小为 4），以获得在分层因素方面每个治疗组的均衡分配。研究调查人员和参与者对治疗分配不知情。患者、调查人员、独立影像学委员会成员和赞助商对 PD-L1 表达状态不知情。主要终点是 PD-L1 阳性人群中的研究者评估无进展生存期和意向治疗（ITT）人群中的总生存期。这项试验在 ClinicalTrials.gov 注册，编号为 NCT02420821。
在 2015 年 5 月 20 日至 2016 年 10 月 12 日期间，共招募了 915 名患者，其中 454 名被随机分配到阿替利珠单抗联合贝伐珠单抗组，461 名被分配到舒尼替尼组。915 名患者中有 362 名（40%）患有 PD-L1 阳性疾病。主要无进展生存期分析时中位随访时间为 15 个月，总生存期中期分析时中位随访时间为 24 个月。在 PD-L1 阳性人群中，阿替利珠单抗联合贝伐珠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，中位总生存期的 HR 为 0.93（0.76-1.14），并且在中期分析时未达到显著水平。阿替利珠单抗联合贝伐珠单抗组中有 182 名（40%）患者和舒尼替尼组中有 240 名（54%）患者发生与治疗相关的 3-4 级不良事件：阿替利珠单抗联合贝伐珠单抗组中有 24 名（5%）患者和舒尼替尼组中有 37 名（8%）患者发生与治疗相关的所有级别不良事件，导致治疗方案中断。
与舒尼替尼相比，阿替利珠单抗联合贝伐珠单抗可延长转移性肾细胞癌患者的无进展生存期，并表现出良好的安全性特征。需要进行更长期的随访，以确定是否会出现生存获益。这些研究结果支持阿替利珠单抗联合贝伐珠单抗作为晚期肾细胞癌患者的一线治疗选择。
罗氏公司和基因泰克公司。
