ObjectiveTo compare the differential efficacy of first‐line immune checkpoint inhibitor (ICI)‐based combined therapies among patients with intermediate‐ and poor‐risk metastatic renal cell carcinoma (mRCC), as recently, the efficacy of triplet therapy comprising nivolumab plus ipilimumab plus cabozantinib has been published.Patients and MethodsThree databases were searched in December 2022 for randomised controlled trials (RCTs) analysing oncological outcomes in patients with mRCC treated with first‐line ICI‐based combined therapies. We performed network meta‐analysis (NMA) to compare the outcomes, including progression‐free survival (PFS) and objective response rates (ORRs), in patients with intermediate‐ and poor‐risk mRCC; we also assessed treatment‐related adverse events.ResultsOverall, seven RCTs were included in the meta‐analyses and NMAs. Treatment ranking analysis revealed that pembrolizumab + lenvatinib (99%) had the highest likelihood of improved PFS, followed by nivolumab + cabozantinib (79%), and nivolumab + ipilimumab + cabozantinib (77%). Notably, compared to nivolumab + cabozantinib, adding ipilimumab to nivolumab + cabozantinib did not improve PFS (hazard ratio 1.02, 95% confidence interval 0.72–1.43). Regarding ORRs, treatment ranking analysis also revealed that pembrolizumab + lenvatinib had the highest likelihood of providing better ORRs (99.7%). The likelihoods of improved PFS and ORRs of pembrolizumab + lenvatinib were true in both International Metastatic RCC Database Consortium (IMDC) risk groups.ConclusionsOur analyses confirmed the robust efficacy of pembrolizumab + lenvatinib as first‐line treatment for patients with intermediate or poor IMDC risk mRCC. Triplet therapy did not result in superior efficacy. Considering both toxicity and the lack of mature overall survival data, triplet therapy should only be considered in selected patients.

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转移性肾细胞癌的一线免疫治疗：更新的网络荟萃分析，包括三联疗法

目的比较一线免疫检查点抑制剂（ICI）联合治疗在中危和低危转移性肾细胞癌（mRCC）患者中的差异疗效，最近，纳武单抗+伊匹单抗+卡博替尼三联疗法的疗效患者和方法于 2022 年 12 月在三个数据库中检索了随机对照试验 (RCT)，这些试验分析了接受一线 ICI 联合疗法治疗的 mRCC 患者的肿瘤学结果。我们进行了网络荟萃分析 (NMA) 来比较中危和低危 mRCC 患者的结果，包括无进展生存期 (PFS) 和客观缓解率 (ORR)；我们还评估了与治疗相关的不良事件。结果总体而言，荟萃分析和 NMA 中纳入了 7 个随机对照试验。治疗排名分析显示，派姆单抗 + 乐伐替尼 (99%) 改善 PFS 的可能性最高，其次是纳武单抗 + 卡博替尼 (79%) 和纳武单抗 + 伊匹单抗 + 卡博替尼 (77%)。值得注意的是，与纳武单抗 + 卡博替尼相比，在纳武单抗 + 卡博替尼中添加伊匹单抗并没有改善 PFS（风险比 1.02，95% 置信区间 0.72–1.43）。关于 ORR，治疗排名分析还显示，pembrolizumab + lenvatinib 提供更好 ORR 的可能性最高 (99.7%)。在两个国际转移性肾细胞癌数据库联盟 (IMDC) 风险组中，派姆单抗 + 乐伐替尼改善 PFS 和 ORR 的可能性都是真实的。结论我们的分析证实了派姆单抗 + 乐伐替尼作为一线治疗对于中度或低度 IMDC 风险 mRCC 患者的稳健疗效。三联疗法并未产生优异的疗效。考虑到毒性和缺乏成熟的总体生存数据，三联疗法仅应在选定的患者中考虑。