Unveiling the best immune checkpoint inhibitor-based therapy for metastatic renal cell carcinoma in the first-line setting: an updated systematic review and Bayesian network analysis

Background: 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. Objective: We aimed to analyz...

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Main Authors: Junpeng Wang, Xin Li, Mengjun Li, Qingyuan Liu, Zixuan Xie, Xiaotian Si, Lei Yang, Zhifeng Wang, Degang Ding
Format: Article
Language:English
Published: SAGE Publishing 2025-07-01
Series:Therapeutic Advances in Medical Oncology
Online Access:https://doi.org/10.1177/17588359251353259
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author Junpeng Wang
Xin Li
Mengjun Li
Qingyuan Liu
Zixuan Xie
Xiaotian Si
Lei Yang
Zhifeng Wang
Degang Ding
author_facet Junpeng Wang
Xin Li
Mengjun Li
Qingyuan Liu
Zixuan Xie
Xiaotian Si
Lei Yang
Zhifeng Wang
Degang Ding
author_sort Junpeng Wang
collection DOAJ
description Background: 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. Objective: We aimed to analyze the updated data to compare the efficacy of all available ICI-based options for mRCC. Design: A systematic review and Bayesian network analysis. Data sources and methods: A systematic literature search was undertaken up to September 15, 2024, and subsequent analysis was performed using a Bayesian fixed-effect model. Results: 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. Conclusion: 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.
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spelling doaj-art-cdcc01cd03fb4001beda1d5232e59ec12025-08-20T02:44:35ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592025-07-011710.1177/17588359251353259Unveiling the best immune checkpoint inhibitor-based therapy for metastatic renal cell carcinoma in the first-line setting: an updated systematic review and Bayesian network analysisJunpeng WangXin LiMengjun LiQingyuan LiuZixuan XieXiaotian SiLei YangZhifeng WangDegang DingBackground: 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. Objective: We aimed to analyze the updated data to compare the efficacy of all available ICI-based options for mRCC. Design: A systematic review and Bayesian network analysis. Data sources and methods: A systematic literature search was undertaken up to September 15, 2024, and subsequent analysis was performed using a Bayesian fixed-effect model. Results: 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. Conclusion: 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.https://doi.org/10.1177/17588359251353259
spellingShingle Junpeng Wang
Xin Li
Mengjun Li
Qingyuan Liu
Zixuan Xie
Xiaotian Si
Lei Yang
Zhifeng Wang
Degang Ding
Unveiling the best immune checkpoint inhibitor-based therapy for metastatic renal cell carcinoma in the first-line setting: an updated systematic review and Bayesian network analysis
Therapeutic Advances in Medical Oncology
title Unveiling the best immune checkpoint inhibitor-based therapy for metastatic renal cell carcinoma in the first-line setting: an updated systematic review and Bayesian network analysis
title_full Unveiling the best immune checkpoint inhibitor-based therapy for metastatic renal cell carcinoma in the first-line setting: an updated systematic review and Bayesian network analysis
title_fullStr Unveiling the best immune checkpoint inhibitor-based therapy for metastatic renal cell carcinoma in the first-line setting: an updated systematic review and Bayesian network analysis
title_full_unstemmed Unveiling the best immune checkpoint inhibitor-based therapy for metastatic renal cell carcinoma in the first-line setting: an updated systematic review and Bayesian network analysis
title_short Unveiling the best immune checkpoint inhibitor-based therapy for metastatic renal cell carcinoma in the first-line setting: an updated systematic review and Bayesian network analysis
title_sort unveiling the best immune checkpoint inhibitor based therapy for metastatic renal cell carcinoma in the first line setting an updated systematic review and bayesian network analysis
url https://doi.org/10.1177/17588359251353259
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