# 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

## TL;DR

This study compares two treatment combinations for advanced kidney cancer and finds no significant difference in effectiveness between them.

## Contribution

The study provides real-world evidence comparing ICI-ICI and ICI-TKI treatments for metastatic renal cell carcinoma.

## Key findings

- No significant differences in survival or response were found between ICI-ICI and ICI-TKI combinations in poor-risk patients.
- In intermediate-risk patients, ICI-TKI showed slightly better progression-free survival, but the difference was not statistically significant.

## Abstract

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 versus ICI-TKI combinations in patients with intermediate- and poor-risk mRCC according to International Metastatic RCC Database Consortium (IMDC).

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.

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 versus 12.9 months (HR 0.87, 95% CI 0.59–1.28, p = 0.49), and median PFS was 6.7 versus 8.7 months (HR 1.10, 95% CI 0.79–1.54, p = 0.53), for ICI-ICI versus ICI–TKI, respectively. In the intermediate-risk patients treated with ICI-ICI versus ICI-TKI, median OS was 37.8 versus 35.5 months (HR 1.08; 95% CI 0.77–1.50; p = 0.65), and median PFS was 17.8 versus 18.6 months (HR 1.29, 95% CI 1.00–1.66, p = 0.050). ORR was 42.9% versus 45.8% in poor-risk patients (OR 0.72, 95% CI 0.39–1.34, p = 0.303) and 48.1% versus 54.3% in intermediate-risk patients (OR 0.71, 95% CI 0.48–1.04, p = 0.075).

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.

The online version contains supplementary material available at 10.1007/s00262-026-04318-x.