New data from the phase 2 CABRAMET trial presented at the 2025 ASCO Genitourinary Cancers Symposium in San Francisco reveals promising outcomes for patients with renal cell carcinoma (RCC) and brain metastases treated with cabozantinib (Cabometyx).
The multicenter, open-label, single-arm study evaluated 26 patients with histologically proven RCC and brain metastases, addressing a critical unmet need in a patient population with historically poor outcomes. Currently, patients with metastatic disease at presentation face a mere 5-year survival rate of 10%, with even more limited options for those with brain metastases.
Significant Clinical Outcomes
The trial demonstrated remarkable efficacy, with a brain metastases progression-free survival rate of 56.0% at 6 months. Particularly noteworthy was the 61.5% partial response rate for brain metastases, with the median response duration not yet reached. At the 24-month mark following brain metastases response, 66.7% of patients remained event-free.
The median follow-up period extended to 39.8 months, during which researchers observed a median progression-free survival of 8.1 months and a brain metastases progression-free survival of 8.4 months. The median overall survival reached 15.8 months.
Treatment Profile and Patient Population
Study participants included patients with brain metastases measuring at least 5 mm (or greater than 8 mm if solitary), with no more than three prior systemic treatments excluding cabozantinib. All patients maintained an ECOG performance status of 0 or 1 and received steroids at doses less than 40 mg per day.
Broader Impact and Context
Cabozantinib, a tyrosine kinase inhibitor, has already established its role in RCC treatment, with FDA approvals both as a monotherapy and in combination with nivolumab. This latest data expands its potential utility to address the challenging subset of patients with brain metastases.
The findings are particularly significant given that RCC accounts for 90% of kidney cancer cases, with one-third of patients diagnosed at an advanced stage. The CABRAMET trial results suggest that cabozantinib could offer a viable systemic therapy option for patients who previously had few alternatives beyond localized treatments.
The study's promising efficacy signals, particularly in managing both intracranial and extracranial disease progression, mark an important step forward in improving outcomes for this high-risk patient population. These results warrant further investigation to optimize treatment strategies and potentially establish cabozantinib as a standard option for RCC patients with brain metastases.
