Effectiveness of ICI-ICI versus ICI-TKI combinations in patients with IMDC intermediate- and poor-risk metastatic renal cell carcinoma: a sub-analysis of the MEET-URO 33 study

Background Immune checkpoint inhibitor doublet (ICI–ICI) and ICI plus tyrosine kinase inhibitor (ICI–TKI) regimens are the cornerstone of treatment for metastatic renal cell carcinoma (mRCC), although no head-to-head comparisons are currently available. This study aimed to compare the real-world effectiveness of ICI-ICI vs ICI-TKI combinations in patients with intermediate- and poor-risk mRCC according to International Metastatic RCC Database Consortium (IMDC). Methods The Meet-URO 33 study is a multicentre retrospective-prospective registry collecting real-world data on patients with mRCC. Multivariable logistic and Cox models were built for objective response rate (ORR), PFS and OS, with a propensity score (PS) adjustment for baseline imbalances. Results Among 1497 patients, 755 were intermediate-risk (199 ICI-ICI, 556 ICI-TKI) and 312 poor-risk (77 ICI-ICI, 212 ICI-TKI). Median follow-up was 14.2 months (8.0 months and 14.5 months in poor- and intermediate-risk subgroups, respectively). In poor-risk patients, median OS was 20.3 vs 12.9 months (HR 0.87, 95% CI: 0.59–1.28, p  = 0.49), and median PFS was 6.7 vs 8.7 months (HR 1.10, 95% CI: 0.79–1.54, p  = 0.53), for ICI–ICI vs ICI–TKI, respectively. In the intermediate-risk patients treated with ICI-ICI vs ICI-TKI, median OS was 37.8 vs 35.5 months (HR: 1.08; 95% CI: 0.77–1.50; p = 0.65), and median PFS was 17.8 vs 18.6 months (HR 1.29, 95% CI: 1.00–1.66, p = 0.050). ORR was 42.9% vs 45.8% in poor-risk patients (OR 0.72, 95% CI: 0.39–1.34, p  = 0.303) and 48.1% vs 54.3% in intermediate-risk patients (OR 0.71, 95% CI: 0.48–1.04, p  = 0.075). Conclusions No statistically significant differences in survival or response were observed between ICI-ICI and ICI-TKI combinations in patients with IMDC intermediate- and poor-risk mRCC.