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Role of Immune Checkpoint Inhibitor-Based Therapies for Metastatic Renal Cell Carcinoma in the First-Line Setting: A Systematic Review and Bayesian Network Analysis

36 Pages Posted: 18 Jun 2019

See all articles by Junpeng Wang

Junpeng Wang

Zhengzhou University

Xin Li

Zhengzhou University

Xiaoqiang Wu

Zhengzhou University - Department of Urology

Zhiwei Wang

Zhengzhou University

Chan Zhang

Zhengzhou University - Department of Urology

Guanghui Cao

Zhengzhou University - Department of Urology

Xiaofan Zhang

Zhengzhou University - Department of Pathophysiology

Feng Peng

Zhengzhou University - Department of Pathophysiology

Tianzhong Yan

Zhengzhou University - Department of Urology

More...

Abstract

Background: Several novel immune checkpoint inhibitor (ICI)-based treatments exhibited promising survival benefits for metastatic renal cell carcinoma (mRCC), yet there is no current guidance regarding the optimum first-line regimen. We performed this network-meta analysis to compare the efficacy and safety of all available treatments for mRCC.

Methods: A systematic search of literature was conducted in April 2019, and the analysis was done on a Bayesian fixed-effect model.

Results: 25 randomized clinical trials (RCTs) involving 13,010 patients were included in this study. The results showed that for overall survival, pembrolizumab plus axitinib (hazard ratio [HR]: 0.53; 95% credible interval [CrI]: 0.38-0.73) and nivolumab plus ipilimumab (HR: 0.63; 95% CrI: 0.50-0.79) were significantly more effective than sunitinib, and pembrolizumab plus axitinib was probably (68%) to be the best choice. For progression-free survival, cabozantinib (HR: 0.66; 95% CrI: 0.46-0.94), pembrolizumab plus axitinib (HR: 0.69; 95% CrI: 0.57-0.84), avelumab plus axitinib (HR: 0.69; 95% CrI: 0.56-0.85), nivolumab plus ipilimumab (HR: 0.82; 95% CrI: 0.68-0.99), and atezolizumab plus bevacizumab (HR: 0.86; 95% CrI: 0.74-0.99) were statistically superior to sunitinib, and cabozantinib was likely (43%) to be the preferred options. Nivolumab plus ipilimumab (OR: 0.50; 95% CrI: 0.28-0.84), and atezolizumab plus bevacizumab (OR: 0.56; 95% CrI: 0.36-0.83) were associated with significantly lower rate of high-grade adverse events than sunitinib.

Conclusions: Our findings demonstrate that pembrolizumab plus axitinib might be the best treatment for mRCC, while nivolumab plus ipilimumab has the most favorable balance between efficacy and acceptability, and may provide new guidance to make treatment decisions.

Funding Statement: This research was supported by the Henan Provincial Scientific and Technological Research Project (Grant No. 192102310036).

Declaration of Interests: The authors declare no conflicts of interest.

Ethics Approval Statement: This study was performed based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) extension statement for network meta-analysis.

Keywords: renal cell carcinoma; first-line systemic therapies; immune checkpoint inhibitor; efficacy; safety

Suggested Citation

Wang, Junpeng and Li, Xin and Wu, Xiaoqiang and Wang, Zhiwei and Zhang, Chan and Cao, Guanghui and Zhang, Xiaofan and Peng, Feng and Yan, Tianzhong, Role of Immune Checkpoint Inhibitor-Based Therapies for Metastatic Renal Cell Carcinoma in the First-Line Setting: A Systematic Review and Bayesian Network Analysis (June 17, 2019). EBioMedicine, Volume 47, September 2019, Pages 78-88, https://doi.org/10.1016/j.ebiom.2019.08.006, Available at SSRN: https://ssrn.com/abstract=3405567 or http://dx.doi.org/10.2139/ssrn.3405567

Junpeng Wang

Zhengzhou University

100 Science Avenue
Zhengzhou, Henan 450001
China

Xin Li

Zhengzhou University

100 Science Avenue
Zhengzhou, Henan 450001
China

Xiaoqiang Wu

Zhengzhou University - Department of Urology ( email )

Zhengzhou, 450003
China

Zhiwei Wang

Zhengzhou University

100 Science Avenue
Zhengzhou, Henan 450001
China

Chan Zhang

Zhengzhou University - Department of Urology

Zhengzhou, 450003
China

Guanghui Cao

Zhengzhou University - Department of Urology

Zhengzhou, 450003
China

Xiaofan Zhang

Zhengzhou University - Department of Pathophysiology

China

Feng Peng

Zhengzhou University - Department of Pathophysiology

China

Tianzhong Yan (Contact Author)

Zhengzhou University - Department of Urology ( email )

Zhengzhou, 450003
China

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