■非透明细胞肾细胞癌(RCC)患者辅助治疗的临床试验数据很少。
■评价肾切除术后依维莫司辅助治疗对局部乳头状和发色细胞肾细胞癌患者无复发生存期(RFS)和总生存期(OS)的影响。
■这是一项3期随机临床试验的预设亚组分析,EVEREST,纳入2011年4月1日至2016年9月15日期间纳入的患者.符合条件的患者在中高风险(pT1等级3-4,N0至pT3a等级1-2,N0)或非常高风险(pT3a等级3-4至pT4任何等级或N)的情况下完全切除了RCC接受了根治性或部分肾切除术。最终分析于2022年3月完成。
■干预组接受了54周的依维莫司(每天口服10mg);对照组接受了匹配的安慰剂。
■主要结果是RFS,操作系统,和不良事件的发生率。为了测试治疗效果的危险比(HR),Cox回归模型用于OS和RFS。
■在1545名初治的成年患者中,非转移性,在EVEREST中完全切除RCC,109例乳头状肾细胞癌(中位[范围]年龄,60[19-81]岁;82[75%]男性;50例[46%]患有极高风险疾病)和99例发色细胞RCC(中位[范围]年龄51[18-71]岁;53[54%]男性;34例[34%]患有极高风险疾病)。干预组57例乳头状RCC患者中,26(46%)完成54周的治疗,在干预组的53例发色肾细胞癌患者中,26(49%)完成54周的医治。中位随访时间(IQR)为76(61-96)个月,与安慰剂相比,佐剂依维莫司在乳头状肾细胞癌中均未改善RFS(5年RFS:62%vs70%;HR,1.19;95%CI,0.61-2.33;P=.61)或发色RCC(5年RFS:79%vs77%;HR,0.89;95%CI,0.37-2.13;P=0.79)。在合并的非清除RCC队列中,在接受依维莫司治疗的患者中,有48%发生了3级或以上的不良事件,在接受安慰剂治疗的患者中,有9%发生了.
■在这项评估使用依维莫司佐剂的临床试验中,术后依维莫司未显示乳头状或发色性肾癌患者RFS改善的证据,研究结果不支持该队列的依维莫司辅助治疗.然而,由于95%CI的下限分别为0.61和0.89,不能排除这些亚组的潜在治疗获益.
■ClinicalTrials.gov标识符:NCT01120249。
UNASSIGNED: Clinical
trial data on adjuvant therapy in patients with non-clear cell renal cell carcinoma (RCC) are scant.
UNASSIGNED: To evaluate the effect of adjuvant everolimus after nephrectomy on recurrence-free survival (RFS) and overall survival (OS) in patients with localized papillary and chromophobe RCC.
UNASSIGNED: This prespecified subgroup analysis of a phase 3 randomized clinical
trial, EVEREST, included patients enrolled between April 1, 2011, and September 15, 2016. Eligible patients had fully resected RCC at intermediate-high risk (pT1 grade 3-4, N0 to pT3a grade 1-2, N0) or very-high risk (pT3a grade 3-4 to pT4 any grade or N+) for recurrence who had received radical or partial nephrectomy. Final analyses was completed in March 2022.
UNASSIGNED: The intervention group received 54 weeks of everolimus (10 mg orally daily); the control group received a matching placebo.
UNASSIGNED: The main outcomes were RFS, OS, and rates of adverse events. For testing the hazard ratio (HR) for treatment effect, a Cox regression model was used for both OS and RFS.
UNASSIGNED: Of 1545 adult patients with treatment-naive, nonmetastatic, fully resected RCC in EVEREST, 109 had papillary RCC (median [range] age, 60 [19-81] years; 82 [75%] male; 50 patients [46%] with very high-risk disease) and 99 had chromophobe RCC (median [range] age 51 [18-71] years; 53 [54%] male; 34 patients [34%] with very high-risk disease). Among 57 patients with papillary RCC in the intervention group, 26 (46%) completed 54 weeks of treatment, and among 53 patients with chromophobe RCC in the intervention group, 26 (49%) completed 54 weeks of treatment. With a median (IQR) follow-up of 76 (61-96) months, adjuvant everolimus did not improve RFS compared with placebo in either papillary RCC (5-year RFS: 62% vs 70%; HR, 1.19; 95% CI, 0.61-2.33; P = .61) or chromophobe RCC (5-year RFS: 79% vs 77%; HR, 0.89; 95% CI, 0.37-2.13; P = .79). In the combined non-clear RCC cohort, grade 3 or higher adverse events occurred in 48% of patients who received everolimus and 9% of patients who received placebo.
UNASSIGNED: In this clinical
trial assessing the use of adjuvant everolimus, postoperative everolimus did not show evidence of improved RFS among patients with papillary or chromophobe RCC, and results from the
study do not support adjuvant everolimus for this cohort. However, since the lower bounds of the 95% CIs were 0.61 and 0.89, respectively, potential treatment benefit in these subgroups cannot be ruled out.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT01120249.