Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial
Pembrolizumab plus axitinib versus sunitinib monotherapy as first-line treatment of advanced renal cell carcinoma (KEYNOTE-426): extended follow-up from a randomised, open-label, phase 3 trial
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DOI：
10.1016/s1470-2045(20)30436-8
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发表时间：
2020-12-01
期刊：
影响因子：
51.1
通讯作者：
Rini, Brian, I
中科院分区：
文献类型：
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作者：
Powles, Thomas;Plimack, Elizabeth R.;Rini, Brian, I
背景资料：KEYNOTE-426研究的第一次中期分析显示，帕博利珠单抗联合阿西替尼治疗初治晚期肾细胞癌的上级疗效优于舒尼替尼单药治疗。本文报告的探索性分析和扩展随访旨在评估帕博利珠单抗加阿西替尼与舒尼替尼单药治疗晚期肾细胞癌患者的长期疗效和安全性。在正在进行的随机、开放标签、3期KEYNOTE-426研究中，成人在16个国家的129个研究中心（医院和癌症中心），招募了18岁以上的未接受过治疗的晚期肾细胞癌透明细胞组织学患者。患者被随机分配（1：1）接受200 mg pembrolizumab静脉注射，每3周一次，最多35个周期，加上5 mg阿西替尼口服，每日两次或50 mg舒尼替尼单药治疗，每日一次口服，每6周为一个周期，持续4周。使用交互式语音应答系统或集成网络应答系统进行随机化，并根据国际转移性肾细胞癌数据库联盟风险状态和地理区域进行分层。主要终点是意向治疗人群的总生存期和无进展生存期。由于在第一次中期分析时满足主要终点，因此使用标称p值报告更新的数据。研究结果：2016年10月24日至2018年1月24日期间，861例患者被随机分配接受帕博利珠单抗+阿西替尼（n=432）或舒尼替尼单药治疗（n=429）。ClinicalTrials.gov中位随访30.6个月（IQR 27.2-34.2），在总生存期方面，观察到帕博利珠单抗+阿西替尼相对于舒尼替尼的持续临床获益（帕博利珠单抗和阿西替尼未达到中位值vs舒尼替尼35.7个月[95% CI 33.3-未达到]）;风险比[HR] 0.68 [95%CI 0.55-0.85]，p=0.0003）和无进展生存期（中位15.4个月[12.7-18.9] vs 11.1个月[9.1-12.5]; 0.71 [0.60-0.84]，p
Background: The first interim analysis of the KEYNOTE-426 study showed superior efficacy of pembrolizumab plus axitinib over sunitinib monotherapy in treatment-naive, advanced renal cell carcinoma. The exploratory analysis with extended follow-up reported here aims to assess long-term efficacy and safety of pembrolizumab plus axitinib versus sunitinib monotherapy in patients with advanced renal cell carcinoma.Methods: In the ongoing, randomised, open-label, phase 3 KEYNOTE-426 study, adults (>= 18 years old) with treatment-naive, advanced renal cell carcinoma with clear cell histology were enrolled in 129 sites (hospitals and cancer centres) across 16 countries. Patients were randomly assigned (1:1) to receive 200 mg pembrolizumab intravenously every 3 weeks for up to 35 cycles plus 5 mg axitinib orally twice daily or 50 mg sunitinib monotherapy orally once daily for 4 weeks per 6-week cycle. Randomisation was done using an interactive voice response system or integrated web response system, and was stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk status and geographical region. Primary endpoints were overall survival and progression-free survival in the intention-to-treat population. Since the primary endpoints were met at the first interim analysis, updated data are reported with nominal p values. This study is registered with ClinicalTrials.gov, NCT02853331.Findings: Between Oct 24, 2016, and Jan 24, 2018, 861 patients were randomly assigned to receive pembrolizumab plus axitinib (n=432) or sunitinib monotherapy (n=429). With a median follow-up of 30.6 months (IQR 27.2-34.2), continued clinical benefit was observed with pembrolizumab plus axitinib over sunitinib in terms of overall survival (median not reached with pembrolizumab and axitinib vs 35.7 months [95% CI 33.3-not reached] with sunitinib); hazard ratio [HR] 0.68 [95% CI 0.55-0.85], p=0.0003) and progression-free survival (median 15.4 months [12.7-18.9] vs 11.1 months [9.1-12.5]; 0.71 [0.60-0.84], p