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.
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.
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.
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.
NCT03967522.
European journal of cancer (Oxford, England : 1990). 2026 Apr 01 [Epub ahead of print]
Sylvie Negrier, Loïc Mourey, Cécile Dalban, Marine Gross-Goupil, Aude Fléchon, Bernard Escudier, Philippe Barthélémy, Stéphane Oudard, Emeline Colomba, Constance Thibault, Alain Ravaud, Christine Chevreau, Helen Jane Boyle, Ellen Blanc, Sylvie Chabaud, David Pérol, Laurence Albiges, Ronan Flippot, Groupe d’Etude des Tumeurs UroGénitale (Urogenital Tumor Study Group, GETUG) investigators
Department of Medical Oncology, Centre Léon Bérard, University Lyon I, Lyon, France. Electronic address: ., Oncopole Claudius Regaud, University Institute of Cancer, IUCT Toulouse-Oncopole, France., Clinical Research and Innovation Department, Centre Léon Bérard, Lyon, France., Department of Medical Oncology, Bordeaux University Hospital, Bordeaux, France., Department of Medical Oncology, Centre Léon-Bérard, Lyon, France., Department of Medical Oncology, Gustave Roussy, Villejuif, France., Department of Medical Oncology, Institut de Cancérologie Strasbourg Europe, Strasbourg, France., Department of Medical Oncology, Hôpital Européen Georges Pompidou, Institut du Cancer Paris CARPEM, AP-HP.Centre-Université Paris Cité, Paris, France; Department of Medical Oncology, Hôpital Européen Georges Pompidou, Institut du Cancer Paris CARPEM, Département d'oncologie médicale, Hôpital européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris - Paris Centre, Paris, France; Université de Paris, Paris 75006, France., Department of Medical Oncology, Gustave Roussy, Villejuif, France; Université Paris Saclay, Paris, France.