Immune-Based Combinations for the Treatment of Metastatic Renal Cell Carcinoma: A Meta-Analysis of Randomised Clinical Trials - Beyond the Abstract

Recent years have witnessed the advent of novel treatment options for metastatic renal cell carcinoma (mRCC), including combination therapies with immune checkpoint inhibitors. Herein, we conducted an up-to-date and comprehensive meta-analysis including recently published data of phase III clinical trials evaluating immune-based combinations in mRCC.

We retrieved all the relevant trials published from 15th June 2008 to 24th February 2021, evaluating immune-based combinations in treatment-naïve mRCC through PubMed/MEDLINE, Cochrane library, and EMBASE; additionally, proceedings of the main international oncological meetings were also searched for relevant abstracts. Outcomes of interest included overall survival (OS), progression-free survival (PFS), complete response (CR) rate, and overall response rate (ORR). Hazard ratios (HRs) and their 95% confidence intervals (CIs) for OS and PFS, and odds ratios (ORs) and 95% CIs for CR rate and ORR, were extracted.

Overall, 6 phase III studies involving 5175 treatment-naïve mRCC patients were available for the meta-analysis. According to our results, the use of immune-based combinations decreased the risk of death by 26% (HR 0.74, 95% CI 0.67-0.81, P < 0.001); similarly, a PFS benefit was observed (HR 0.68, 95% CI 0.54-0.85, P < 0.001). In addition, immune-based combinations showed better CR rate and ORR, with ORs of 3.04 (95% CI 2.31-3.99, P < 0.001) and 2.53 (95% CI 1.77-3.62, P < 0.03), respectively.

The results of our meta-analysis confirm the clinical benefit provided by immunotherapy combinations, with CR rate more than tripled in mRCCs receiving immune-based combinations. Further studies in a real-world setting are warranted to validate the findings of our meta-analysis, the most updated to systematically evaluate immune-based combinations in mRCC.

Written by: Francesco Massari, MD, Dirigente Medico, U.O. Oncologia Medica IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bolognam, Italy

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