Treatment options in first-line metastatic renal carcinoma: A meta-analysis of 2556 patients treated with immune checkpoint inhibitors-based combinations in randomised controlled trials

Background & aims: The average five-year survival of metastatic renal cell carcinoma (mRCC) is 71%. However, there is significant variability in patient prognosis. Immune checkpoint inhibitors (ICIs) have been introduced into the treatment landscape of mRCC. This meta-analysis aimed to estimate progression-free and overall survival probabilities and identify possible outcome predictors of mRCC patients treated with ICI combination as first-line treatment. Methods: Studies comparing the combination of ICI combinations versus standard of therapy for first-line treatment of advanced renal-cell carcinoma were searched in MEDLINE, CANCERLIT, the Cochrane Controlled Trials Register, and the Cochrane Library from inception through September 2023. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using the DerSimonian and Laird methods. Results: Six studies met the inclusion criteria. Globally, 5121 patients were included in this meta-analysis: 2556 patients treated with immune checkpoint inhibitors and 2565 with sunitinib as control. The ICI combination was associated with improved PFS (hazard ratio (HR) 0.68; 95 % confidence interval (CI), 0.56-0.81, p < 0.0001). Furthermore, ICI combination was also associated with OS improvement (HR 0.85; 95 % CI, 0.78-0.92, p = 0.001). There is no statistical increase in adverse events. Conclusions: Our findings show that PFS and OS are statistically increased in mRCC with ICI combination treatment by 32% and 15%, respectively.