Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma
Lenvatinib plus Pembrolizumab or Everolimus for Advanced Renal Cell Carcinoma
复制标题
DOI：
10.1056/nejmoa2035716
复制
发表时间：
2021-04-08
影响因子：
158.5
通讯作者：
Choueiri, Toni K.
中科院分区：
文献类型：
--
作者：
Motzer, Robert;Alekseev, Boris;Choueiri, Toni K.
背景乐伐替尼与帕博利珠单抗或依维莫司联合治疗对晚期肾细胞癌具有活性。与舒尼替尼相比，这些方案的疗效尚不清楚。METHODS在这项3期试验中，我们将晚期肾细胞癌患者随机（以1：1：1的比例）分配，既往未接受过全身治疗，接受乐伐替尼（20 mg口服，每日一次）+帕博利珠单抗（200 mg静脉注射，每3周一次），乐伐替尼（18 mg口服，每日一次）+依维莫司（5 mg口服，每日一次），或舒尼替尼（50 mg口服，每日一次，交替4周接受治疗和2周不治疗）。主要终点是无进展生存期，由独立审查委员会根据实体瘤疗效评价标准第1.1版进行评估。总生存率和安全性也进行了评估。共有1069名患者随机分配接受乐伐替尼+帕博利珠单抗（355名患者），乐伐替尼+依维莫司（357名患者）或舒尼替尼（357名患者）。乐伐替尼联合帕博利珠单抗的无进展生存期长于舒尼替尼（中位数，23.9个月vs. 9.2个月;疾病进展或死亡的风险比，0.39; 95%置信区间[CI]，0.32 - 0.49; P
BACKGROUNDLenvatinib in combination with pembrolizumab or everolimus has activity against advanced renal cell carcinoma. The efficacy of these regimens as compared with that of sunitinib is unclear.METHODSIn this phase 3 trial, we randomly assigned (in a 1:1:1 ratio) patients with advanced renal cell carcinoma and no previous systemic therapy to receive lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously once every 3 weeks), lenvatinib (18 mg orally once daily) plus everolimus (5 mg orally once daily), or sunitinib (50 mg orally once daily, alternating 4 weeks receiving treatment and 2 weeks without treatment). The primary end point was progression-free survival, as assessed by an independent review committee in accordance with Response Evaluation Criteria in Solid Tumors, version 1.1. Overall survival and safety were also evaluated.RESULTSA total of 1069 patients were randomly assigned to receive lenvatinib plus pembrolizumab (355 patients), lenvatinib plus everolimus (357), or sunitinib (357). Progression-free survival was longer with lenvatinib plus pembrolizumab than with sunitinib (median, 23.9 vs. 9.2 months; hazard ratio for disease progression or death, 0.39; 95% confidence interval [CI], 0.32 to 0.49; P