Park Sohyeon, Park Kalynn, Kim Chaeyoon, Rhie Sandy Jeong
Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea.
Crit Rev Oncol Hematol. 2025 Apr;208:104630. doi: 10.1016/j.critrevonc.2025.104630. Epub 2025 Jan 27.
Despite numerous meta-analyses comparing the efficacy and safety of immunotherapy-based combination therapies, the optimal therapeutic combinations remain unclear. This study aims to evaluate the optimal application of all immunotherapy-based combination therapy for advanced/metastatic renal cell carcinoma, focusing on efficacy and safety.
We systemically searched the Web of Science, Cochrane Library, and PubMed for studies regarding the first-line immunotherapy-based combination therapy in patients with advanced or metastatic renal cell carcinoma until April 15, 2024. We used network meta-analysis using a random effect model to facilitate direct and indirect treatment comparisons across outcomes.
Seven clinical studies, including 5542 patients with metastatic renal cell carcinoma, were included in the network meta-analysis analysis. Regarding progression-free survival and overall survival, combined Toripalimab + Axitinib significantly outperformed other immunotherapy-based combination therapies. This regimen significantly improved progression-free survival in the intermediate/poor risk group when stratified by prognosis prediction risks compared to sunitinib alone. For the objective response rate, Avelumab + Axitinib was the most preferred strategy in the favorable-risk group, while Nivolumab + Cabozantinib was favored in the intermediate/poor-risk group compared to other immunotherapy-based combinations. The combinations of Nivolumab + Ipilimumab and Atezolizumab + Bevacizumab had favorable safety profiles.
Immunotherapy-based combination therapies significantly improved progression-free survival, overall survival and objective response rate in patients with metastatic renal cell carcinoma compared to sunitinib monotherapy. However, careful monitoring and personalized treatment strategies are required to balance efficacy and safety in patients with underlying conditions. Future research should focus on optimizing treatment protocols and elucidating the mechanisms of adverse events.
尽管有大量的荟萃分析比较了基于免疫疗法的联合疗法的疗效和安全性，但最佳治疗组合仍不明确。本研究旨在评估所有基于免疫疗法的联合疗法在晚期/转移性肾细胞癌中的最佳应用，重点关注疗效和安全性。
我们系统检索了Web of Science、Cochrane图书馆和PubMed，以查找截至2024年4月15日关于晚期或转移性肾细胞癌患者一线基于免疫疗法的联合疗法的研究。我们使用随机效应模型进行网络荟萃分析，以促进不同治疗方案在各项结局上的直接和间接比较。
网络荟萃分析纳入了7项临床研究，共5542例转移性肾细胞癌患者。在无进展生存期和总生存期方面，特瑞普利单抗+阿昔替尼联合治疗显著优于其他基于免疫疗法的联合疗法。与单独使用舒尼替尼相比，按预后预测风险分层时，该方案在中/低风险组中显著改善了无进展生存期。在客观缓解率方面，阿维鲁单抗+阿昔替尼是低风险组中最优选的策略，而与其他基于免疫疗法的联合治疗相比，纳武利尤单抗+卡博替尼在中/低风险组中更受青睐。纳武利尤单抗+伊匹木单抗和阿替利珠单抗+贝伐单抗的联合治疗具有良好的安全性。
与舒尼替尼单药治疗相比，基于免疫疗法的联合疗法显著改善了转移性肾细胞癌患者的无进展生存期、总生存期和客观缓解率。然而，对于有基础疾病的患者，需要仔细监测并采取个性化治疗策略以平衡疗效和安全性。未来的研究应侧重于优化治疗方案并阐明不良事件的机制。
