Background: The phase II trial CABRAMET evaluates the efficacy of the VEGFR tyrosine kinase inhibitor (TKI) cabozantinib in patients with non-locally pretreated brain metastases (BM) from renal cell carcinoma (RCC). Faced with historical challenges in treating BM in RCC, this study aimed to provide prospective data on systemic treatment outcomes.
Patients and methods: This multicenter open-label trial included RCC patients with BM with less than three prior systemic treatments excluding cabozantinib. Eligible patients received 60mg/day oral cabozantinib with dose adjustments for toxicity. The primary endpoint was the 6-month progression-free rate in brain metastases (6m-BM-PFR). The main secondary endpoints included BM objective response rate (ORR) and response duration in BM, extra-cranial ORR, BM and overall progression-free survival (PFS), overall survival (OS), and safety.
Results: The study enrolled 26 patients, with a median follow-up of 38.8 months (range 28.3-52.7 months). The 6m-BM-PFR was 56% (unilateral 95%CI 37.9-) by central review. BM partial responses were achieved in 16/26 patients (BM ORR of 61.5%) by investigator assessment. The median BM response duration was not reached and 58.3% (95%CI 29.3-78.9%) of the patients were event-free at 24 months. The median BM-PFS was 10.7 (95%CI 5.4-NR) months, and the median overall PFS was 8.1 (95%CI 4-11.9) months. The median OS was 15.0 (95%CI 9.3-35.0) months. Cabozantinib exhibited significant efficacy as first-line treatment with BM ORR of 86%, 67% in patients with prior immunotherapy, 40% in patients previously treated with TKI.
Conclusion: The CABRAMET trial is the first to prospectively assess cabozantinib in the challenging population of non-locally pretreated brain metastases from RCC, highlighting its prolonged efficacy and tolerability in selected patients with BM.
Clinical trial registration: NCT03967522.
Keywords: Brain metastases; Cabozantinib; Renal cell carcinoma; Systemic treatment.
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