Comparison of IO-TKI vs IO-IO combinations in IMDC poor-risk metastatic renal cell carcinoma (mRCC) patients (Meet-URO 33 analysis).

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 .