本文由小咖机器人翻译整理

期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2312695

摘要内容如下：

背景

在KEYNOTE-564试验中，肾细胞癌手术后的辅助pembrolizumab治疗在无病生存率显著改善的基础上获得批准。该试验第三次预先指定的中期分析的总生存率结果是否也有利于pembrolizumab尚不确定。

方法

在这项3期、双盲、安慰剂对照试验中，我们将术后复发风险增加的透明细胞肾细胞癌患者随机分配（按1:1的比例）接受pembrolizumab（剂量为200 mg）或安慰剂治疗，每3周一次，最多17个周期（约1年）或直至复发、出现不可接受的毒性作用或撤回同意书。根据研究者的评估（主要终点），先前显示无病生存率显著改善。总生存率是关键的次要终点。安全性是次要终点。

结果

共有496名参与者接受pembrolizumab治疗，498名参与者接受安慰剂治疗。截至2023年9月15日，中位随访时间为57.2个月。无病生存获益与之前的分析一致（复发或死亡的风险比为0.72；95%置信区间[CI]，0.59至0.87）。与安慰剂相比，pembrolizumab显著提高了总生存率（死亡风险比为0.62；95%可信区间为0.44~0.87；P=0.005）。与安慰剂组的86.0%相比，pembrolizumab组估计的48个月总生存率为91.2%。关键亚组的益处是一致的。Pembrolizumab与任何原因的严重不良事件（20.7%，安慰剂组为11.5%）以及与Pembrolizumab或安慰剂相关的3级或4级不良事件（18.6%vs.1.2%）的发生率较高相关。Pembrolizumab治疗未导致死亡。

结论

与安慰剂相比，在术后复发风险增加的透明细胞肾细胞癌患者中，辅助pembrolizumab与总生存率的显著和有临床意义的改善相关。（由Merck的子公司Merck Sharp and Dohme资助；Keynote-564 ClinicalTrials.gov编号，NCT03142334。）

英文原文如下：

Abstracts

BACKGROUND  Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma was approved on the basis of a significant improvement in disease-free survival in the KEYNOTE-564 trial. Whether the results regarding overall survival from the third prespecified interim analysis of the trial would also favor pembrolizumab was uncertain.

METHODS  In this phase 3, double-blind, placebo-controlled trial, we randomly assigned (in a 1:1 ratio) participants with clear-cell renal-cell carcinoma who had an increased risk of recurrence after surgery to receive pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks for up to 17 cycles (approximately 1 year) or until recurrence, the occurrence of unacceptable toxic effects, or withdrawal of consent. A significant improvement in disease-free survival according to investigator assessment (the primary end point) was shown previously. Overall survival was the key secondary end point. Safety was a secondary end point.

RESULTS  A total of 496 participants were assigned to receive pembrolizumab and 498 to receive placebo. As of September 15, 2023, the median follow-up was 57.2 months. The disease-free survival benefit was consistent with that in previous analyses (hazard ratio for recurrence or death, 0.72; 95% confidence interval [CI], 0.59 to 0.87). A significant improvement in overall survival was observed with pembrolizumab as compared with placebo (hazard ratio for death, 0.62; 95% CI, 0.44 to 0.87; P = 0.005). The estimated overall survival at 48 months was 91.2% in the pembrolizumab group, as compared with 86.0% in the placebo group; the benefit was consistent across key subgroups. Pembrolizumab was associated with a higher incidence of serious adverse events of any cause (20.7%, vs. 11.5% with placebo) and of grade 3 or 4 adverse events related to pembrolizumab or placebo (18.6% vs. 1.2%). No deaths were attributed to pembrolizumab therapy.

CONCLUSIONS  Adjuvant pembrolizumab was associated with a significant and clinically meaningful improvement in overall survival, as compared with placebo, among participants with clear-cell renal-cell carcinoma at increased risk for recurrence after surgery. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.).

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