Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma
Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma
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DOI：
10.1056/nejmoa2106391
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发表时间：
2021-08-19
影响因子：
158.5
通讯作者：
Powles, T.
中科院分区：
文献类型：
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作者：
Choueiri, T. K.;Tomczak, P.;Powles, T.
接受肾切除术的肾细胞癌的背景患者没有选择辅助治疗的选择，可以降低具有高水平支持证据的复发风险。方法是双盲，第3阶段试验，我们以1：1的比例随机分配，以1：1的比例随机分配肾切除术后有或没有转移切除术的透明细胞肾细胞癌患者患有高风险辅助Pembrolizumab（剂量为200 mg）或安慰剂每3周静脉注射一次，最多17个周期（约1年）。根据研究者的评估，主要终点是无病生存。总体生存是关键的次要终点。安全是次要终点。总共有496例患者被随机分配接受pembrolizumab，498例接受安慰剂。在预先指定的临时分析中，从随机分组到数据切割日期的中位时间为24.1个月。 pembrolizumab治疗与安慰剂相比明显更长的无病生存期（24个月的无疾病生存，77.3％vs. 68.1％；复发或死亡的危害比率为0.68； 95％置信区间[CI]，0.53至0.87； p = 0.002 [双面]）。 pembrolizumab组的24个月生命患者的估计百分比为96.6％，安慰剂组为93.5％（死亡危险比为0.54； 95％CI，0.30至0.96）。 32.4％的接受pembrolizumab的患者和接受安慰剂的患者中有17.7％发生了任何原因的3年级或更高的不良事件。与安慰剂相比，与安慰剂相比，肾脏无症状的肾脏症患者的复发率很高，与安慰剂相比，无脑脑瘤治疗没有发生与pembrolizumab治疗有关的死亡。
BACKGROUNDPatients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence.METHODSIn a double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with clear-cell renal-cell carcinoma who were at high risk for recurrence after nephrectomy, with or without metastasectomy, to receive either adjuvant pembrolizumab (at a dose of 200 mg) or placebo intravenously once every 3 weeks for up to 17 cycles (approximately 1 year). The primary end point was disease-free survival according to the investigator's assessment. Overall survival was a key secondary end point. Safety was a secondary end point.RESULTSA total of 496 patients were randomly assigned to receive pembrolizumab, and 498 to receive placebo. At the prespecified interim analysis, the median time from randomization to the data-cutoff date was 24.1 months. Pembrolizumab therapy was associated with significantly longer disease-free survival than placebo (disease-free survival at 24 months, 77.3% vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval [CI], 0.53 to 0.87; P = 0.002 [two-sided]). The estimated percentage of patients who remained alive at 24 months was 96.6% in the pembrolizumab group and 93.5% in the placebo group (hazard ratio for death, 0.54; 95% CI, 0.30 to 0.96). Grade 3 or higher adverse events of any cause occurred in 32.4% of the patients who received pembrolizumab and in 17.7% of those who received placebo. No deaths related to pembrolizumab therapy occurred.CONCLUSIONSPembrolizumab treatment led to a significant improvement in disease-free survival as compared with placebo after surgery among patients with kidney cancer who were at high risk for recurrence.