Cabozantinib (CABO) after prior immune checkpoint inhibitor (ICI) and tyrosine-kinase inhibitors (TKI) therapy in metastatic renal cell carcinoma (mRCC): Real-world evidence (RWE) from a Moscow observational program.

e16526 Background: Cabozantinib is approved for metastatic renal cell carcinoma (mRCC). Data of CABO efficacy after prior ICI/ICI-TKI therapy are limited by several RWE trials. Here we report real-world evidence of CABO in Russian patients from a Moscow observational program. Methods: Patients (pts) with mRCC treated with CABO monotherapy through the Moscow observational prospective program between Feb’2022 and Jan’2024 were identified. All pts received 1-3 prior lines of therapy, all received prior ICI and TKI, either in combination or consequently. Pts with active CNS metastases were excluded from the program. Baseline clinical and treatment characteristics were collected. Rates of partial response (PR), stable disease (SD), progressive disease (PD), and disease control rate (DCR, PR+SD) were analyzed, and survival outcomes (overall survival (OS) and progression-free survival (PFS)) were calculated. Results: A total 59 patients (pts) treated with CABO were included in our analysis. Median age was 59 years (range 40-78), 46 (78%) pts were male, 54 (91,5%) pts had clear-cell histology. At time of CABO start 5 pts (8,5%) had the ECOG PS 0, 37 pts (62,7%) had ECOG PS 1, 17 pts (28,8%) had ECOG PS 2. 40 pts (67,8%) had intermediate International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk, 19 pts (32,2%) had poor IMDC risk. 45 (76,3%) pts had prior nephrectomy. 15 pts (25,4%), 27 pts (45,8%), 17 pts (28,8%) had 1, 2 and ≥3 previous treatment lines respectively; 22 pts (37%) received prior treatment with combination of ICI and TKI. 4 pts (7%), 26 pts (44%), 29 pts (49%) had 1, 2-3 and > 3 sites of metastases respectively. 31 pts (53%) had bone metastases. Median (min-max) follow-up was 14 (1-22) months (mo). Rates of best response were: PR - 20%, SD - 56%, PD - 19%. Overall DCR was 76%. Median PFS was 14 mo (12,3-15,7) with 12-mo PFS 59%. Median OS was not reached, and the 12-mo OS rate was 76%. 41% of patients had a dose reduction, 32% needed treatment interruption and 19% of pts discontinued treatment due to toxicity. Conclusions: The effectiveness of CABO observed in this real-world observational program was consistent with results from clinical trials: DCR – 76%, median PFS – 14 mo with 12-mo PFS 59% and 12-mo OS 76%. Dose modifications may be required to optimize CABO use in routine clinical practice.