Immunotherapy-based combinations versus standard first-line treatment for metastatic clear cell renal cell carcinoma: a systematic review and meta-analysis

Purpose: Considering the recent publication of the results of several clinical trials for metastatic clear cell renal cell carcinoma (mRCC), we performed a systematic review and meta-analysis of randomized studies comparing standard first-line VEGFR-targeted therapy to immune checkpoint inhibitors-based combinations for mRCC patients. Methods: 3960 patients from 5 randomized clinical trials where available for evaluation. Result: In the all-comers population, immunotherapy-based combinations were able to decrease the risk of death over the standard of care by 26% (HR 0.74; 95% CI 0.60–0.92; p = 0.006), to decrease the risk of progression by 21% (HR 0.79; 95% CI 0.72–0.86; p < 0.00001), and to increase the relative risk of response by 40% (HR 1.40; 95% CI 1.11–1.77; p = 0.006). For poor/intermediate-risk patients, the risk of death is decreased by 41% and the risk of progression by 27%. Conclusions: The benefit of immunotherapy-based combinations in mRCC patients is independent from the IMDC risk group, but it is stronger for poor/intermediate-risk patients.