美国俄勒冈健康与科学大学Christopher W Ryan团队研究了肾细胞癌切除术后使用依维莫司对患者预后的影响。该研究于2023年7月28日发表在《柳叶刀》杂志上。

接受肾细胞癌切除术的患者有疾病复发的风险。研究组评估了手术后使用哺乳动物雷帕霉素抑制剂依维莫司作为靶点的有效性。

在这项随机、双盲、3期临床试验中，研究组在美国398个学术和社区机构中心招募经组织学证实的肾细胞癌成年人，他们接受了完全手术切除，复发风险中等或极高。肾切除术后，通过基于网络的中央应用程序，使用动态平衡算法，将患者随机分配（1:1），接受每天10 mg口服依维莫司或安慰剂治疗，为期54周。主要终点是无复发生存率。疗效分析包括所有符合条件的随机分配患者；安全性分析包括所有接受治疗的患者。

2011年4月1日至2016年9月15日，共有1545名患者被随机分配接受依维莫司（n=775）或安慰剂（n=770）治疗，其中755名患者被分配接受依维莫司治疗，744名患者接受安慰剂治疗，符合纳入疗效分析的条件。中位随访期为76个月，依维莫司的无复发生存期比安慰剂更长（5年无复发生存率67% vs 63%；分层对数秩p=0.050；分层危险比[HR]为0.85，p=0.051），但不符合预先指定的统计学显著性p值0.044。

在极高风险组中，依维莫司的无复发生存期比安慰剂更长（HR为0.79；p=0.022），但在中高风险组中没有（0.99；p=0.96）。740名接受依维莫司治疗的患者中有343名（46%）发生了3级或更高级别的不良事件，723名接受安慰剂治疗的患者有79名（11%）发生了不良事件。

研究结果表明，在肾切除术后复发风险较高的肾细胞癌患者中，与安慰剂相比，依维莫司术后无复发生存率没有提高。这些结果不支持依维莫司在手术后辅助治疗肾细胞癌。

附：英文原文

Title: Adjuvant everolimus after surgery for renal cell carcinoma (EVEREST): a double-blind, placebo-controlled, randomised, phase 3 trial

Author: Christopher W Ryan, Catherine M Tangen, Elisabeth I Heath, Mark N Stein, Maxwell V Meng, Ajjai S Alva, Sumanta K Pal, Igor Puzanov, Joseph I Clark, Toni K Choueiri, Neeraj Agarwal, Robert G Uzzo, Naomi B Haas, Timothy W Synold, Melissa Plets, Ulka N Vaishampayan, Brian M Shuch, Ian M Thompson, Primo N Lara

Issue&Volume: 2023-07-28

Abstract:

Background

Patients undergoing resection of renal cell carcinoma are at risk of disease relapse. We evaluated the effectiveness of the mammalian target of rapamycin inhibitor everolimus administered after surgery.

Methods

In this randomised, double-blind, phase 3 trial, we enrolled adults with histologically confirmed renal cell carcinoma who had undergone a full surgical resection and were at intermediate-high or very high risk of recurrence at 398 academic and community institution centres in the USA. After nephrectomy, patients were randomly assigned (1:1) via a central web-based application using a dynamic balancing algorithm to receive 10 mg oral everolimus daily or placebo for 54 weeks. The primary endpoint was recurrence-free survival. Efficacy analyses included all eligible, randomly assigned patients; safety analysis included all patients who received treatment. This trial is registered with ClinicalTrials.gov, NCT01120249 and is closed to new participants.

Findings

Between April 1, 2011, and Sept 15, 2016, a total of 1545 patients were randomly assigned to receive everolimus (n=775) or placebo (n=770), of whom 755 assigned to everolimus and 744 assigned to placebo were eligible for inclusion in the efficacy analysis. With a median follow-up of 76 months (IQR 61–92), recurrence-free survival was longer with everolimus than with placebo (5-year recurrence-free survival 67% [95% CI 63–70] vs 63% [60–67]; stratified log-rank p=0·050; stratified hazard ratio [HR] 0·85, 95% CI 0·72–1·00; p=0·051) but did not meet the prespecified p value for statistical significance of 0·044. Recurrence-free survival was longer with everolimus than with placebo in the very-high-risk group (HR 0·79, 95% CI 0·65–0·97; p=0·022) but not in the intermediate-high-risk group (0·99, 0·73–1·35; p=0·96). Grade 3 or higher adverse events occurred in 343 (46%) of 740 patients who received everolimus and 79 (11%) of 723 who received placebo.

Interpretation

Postoperative everolimus did not improve recurrence-free survival compared with placebo among patients with renal cell carcinoma at high risk of recurrence after nephrectomy. These results do not support the adjuvant use of everolimus for renal cell carcinoma after surgery.

DOI: 10.1016/S0140-6736(23)00913-3

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00913-3/fulltext