Wang Junpeng, Li Xin, Li Mengjun, Liu Qingyuan, Xie Zixuan, Si Xiaotian, Yang Lei, Wang Zhifeng, Ding Degang
Department of Urology, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.
Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
Ther Adv Med Oncol. 2025 Jul 6;17:17588359251353259. doi: 10.1177/17588359251353259. eCollection 2025.
Immune checkpoint inhibitor (ICI)-based combination therapies have been recommended as first-line options for metastatic renal cell carcinoma (mRCC); however, no head-to-head randomized controlled trials (RCTs) have compared all existing ICI-based therapies.
We aimed to analyze the updated data to compare the efficacy of all available ICI-based options for mRCC.
A systematic review and Bayesian network analysis.
A systematic literature search was undertaken up to September 15, 2024, and subsequent analysis was performed using a Bayesian fixed-effect model.
This study included 30 RCTs involving 14,959 patients. The results revealed that nivolumab plus cabozantinib (hazard ratio (HR): 0.77; 95% credible interval (CrI): 0.63-0.93), pembrolizumab plus lenvatinib (HR: 0.79; 95% CrI: 0.64-0.99), toripalimab plus axitinib (HR: 0.62; 95% CrI: 0.42-0.97), nivolumab plus ipilimumab (HR: 0.72; 95% CrI: 0.62-0.84), pembrolizumab plus axitinib (HR: 0.84; 95% CrI: 0.71-0.98), and avelumab plus axitinib (HR: 0.79; 95% CrI: 0.64-0.98) were significantly more effective than sunitinib for overall survival (OS). Most ICI-based combination treatments resulted in fewer or similar high-grade adverse events compared to sunitinib, except for pembrolizumab plus lenvatinib. For favorable-risk patients, ICI-based combination therapies were not more effective than sunitinib in OS, while six ICI-based combination therapies were associated with significantly improved OS compared to sunitinib for intermediate-risk or poor-risk patients.
Our findings demonstrated that combination therapies including nivolumab plus cabozantinib, pembrolizumab plus lenvatinib, toripalimab plus axitinib, nivolumab plus ipilimumab, pembrolizumab plus axitinib, and avelumab plus axitinib significantly improved OS versus sunitinib. For subgroup analysis, ICI-based combination therapies exhibited significant advantages over sunitinib for intermediate-risk or poor-risk patients, while such advantages were diminished in treating favorable-risk patients.
基于免疫检查点抑制剂（ICI）的联合疗法已被推荐作为转移性肾细胞癌（mRCC）的一线治疗选择；然而，尚无直接比较所有现有基于ICI疗法的头对头随机对照试验（RCT）。
我们旨在分析更新数据，以比较所有可用的基于ICI的mRCC治疗方案的疗效。
系统评价和贝叶斯网络分析。
截至2024年9月15日进行系统文献检索，并使用贝叶斯固定效应模型进行后续分析。
本研究纳入30项RCT，涉及14959例患者。结果显示，纳武利尤单抗联合卡博替尼（风险比（HR）：0.77；95%可信区间（CrI）：0.63 - 0.93）、帕博利珠单抗联合乐伐替尼（HR：0.79；95% CrI：0.64 - 0.99）、替雷利珠单抗联合阿昔替尼（HR：0.62；95% CrI：0.42 - 0.97）、纳武利尤单抗联合伊匹木单抗（HR：0.72；95% CrI：0.62 - 0.84）、帕博利珠单抗联合阿昔替尼（HR：0.84；95% CrI：0.71 - 0.98）以及阿维鲁单抗联合阿昔替尼（HR：0.79；95% CrI：0.64 - 0.98）在总生存期（OS）方面显著优于舒尼替尼。与舒尼替尼相比，大多数基于ICI的联合治疗导致的高级别不良事件更少或相似，但帕博利珠单抗联合乐伐替尼除外。对于低风险患者，基于ICI的联合疗法在OS方面并不比舒尼替尼更有效，而对于中风险或高风险患者，六种基于ICI的联合疗法与舒尼替尼相比OS显著改善。
我们的研究结果表明，纳武利尤单抗联合卡博替尼、帕博利珠单抗联合乐伐替尼、替雷利珠单抗联合阿昔替尼、纳武利尤单抗联合伊匹木单抗、帕博利珠单抗联合阿昔替尼以及阿维鲁单抗联合阿昔替尼的联合疗法与舒尼替尼相比显著改善了OS。对于亚组分析，基于ICI的联合疗法在治疗中风险或高风险患者方面相对于舒尼替尼具有显著优势，而在治疗低风险患者时这种优势减弱。
