Comparison of IO-TKI vs IO-IO combinations in IMDC poor-risk metastatic renal cell carcinoma (mRCC) patients (Meet-URO 33 analysis).
Authors: Sara Elena Rebuzzi, Alessio Signori, Sebastiano Buti, Alberto Dalla Volta, Martina Fanelli, Valeria Sardaro, Marilena Di Napoli, Cristina Masini, Annalisa Guida, Roberto Filippi, Silvia Chiellino, Carlo Messina, Sarah Scagliarini, Emanuela Fantinel, Lucia Bonomi, Vincenza Conteduca, Filippo Maria Deppieri, Mariella Sorarù, Giuseppe Fornarini, Davide Bimbatti
Journal: Journal of Clinical Oncology (2025)

495 Background: Immune-combinations have become the cornerstone of the mRCC treatment landscape, but head-to-head comparisons between the different first-line treatment strategies are lacking and few real-world data are available in this setting. In this context, little evidence is available, especially for IMDC poor-risk patients, who have the worst prognosis and lowest response to standard treatments. Methods: The Meet-URO 33 study is an Italian retrospective/prospective registry of the first-line setting of mRCC patients from January 2021 (Trial registration: CESC IOV 2023-78, PMID: 38914928) with the aim to answer as many clinical questions as possible. This analysis focused on assessing the different performance of IO-TKI and IO-IO combinations in terms of survival and response outcomes and the differential baseline clinical characteristics in the two treatment groups. Results: Among 892 patients enrolled from 40 Italian centres, 772 patients (87%) were evaluable for survival analyses; 160 patients (21%) had IMDC poor risk: 42 (26%) received IO-IO, 105 (66%) IO-TKI and 13 (8%) TKI. Comparing the baseline clinical characteristics of patients included in the two immune-combinations, poor-risk patients receiving IO-IO were older (mean age: 68 vs 64, p=0.03), had more cardiovascular comorbidities (74% vs 56%, p=0.048) and lower frequency of bone metastases (29% vs 57%, p=0.002). After a mFUP of 6.9 months (mo), the mOS of all poor-risk patients was 11.3 months, higher with IO-IO than with IO-TKI [20.6 vs 11 mo, HR 1.65 (0.97-2.82); p=0.067]. After multivariable analysis (age, comorbidities, ECOG, bone metastases) the difference between IO-TKI and IO-IO was not statistically significant [HR 1.37 (0.78-2.40); p=0.27]. The overall mPFS was 6.4 mo, higher with IO-IO compared with IO-TKI [11 vs 5.8 mo, HR 1.70 (1.05-2.75); p=0.031]. After the multivariable analysis, the difference between the two treatment groups lost statistical significance [HR 1.58 (0.95-2.63); p=0.078]. The general ORR was 46%, higher with IO-TKI than with IO-IO [71% vs 29%, OR 0.70 (0.21-1.56); p=0.38]. Conclusions: These preliminary analyses of the ongoing Meet-URO 33 study show no clear survival advantage in using an IO-TKI combinations instead of an IO-IO combination in IMDC poor-risk patients. These results are in line with the well-known smaller benefit of TKI in poor-risk patients (more immunogenic / less angiogenic patterns and results of the COSMIC-313 study). A longer follow-up is needed to examine in depth the different performance of immune-combinations in IMDC poor-risk patients. Clinical trial information: CESC IOV 2023-78 .