Cabozantinib shows intracranial activity in RCC patients with brain metastases


According to a retrospective study published in JAMA Oncology.

The study included 88 patients with RCC and brain metastases who were treated at 15 international institutions between January 2014 and October 2020. The median age of patients at initiation of cabozantinib was 61 years (range, 34- 81 years old), and most were men (78%).

The patients were divided into cohorts A and B. Cohort A consisted of 33 patients who had evidence of intracranial progression without concomitant local brain-directed therapy at the start of cabozantinib treatment. The median time from prior brain-directed therapy to the start of cabozantinib was 5 months in this group.

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Cohort B consisted of 55 patients, 35 who showed signs of progression with concomitant local treatment directed to the brain and 20 who had stable intracranial disease at the start of cabozantinib treatment. Concomitant treatment consisted of stereotaxic radiosurgery (n = 26), whole brain radiation therapy (n = 7) and / or neurosurgery (n = 5).

At a median follow-up of 17 months, the objective intracranial response rate was 55% in cohort A (3 complete responses [CRs] and 14 partial responses [PRs]) and 47% in cohort B (1 CR and 24 PR).

The extracranial response rate was 48% in cohort A (16 PR) and 38% in cohort B (1 CR and 24 PR). The median time to treatment failure was 8.9 months in cohort A and 9.7 months in cohort B.

The median overall survival was 15 months in cohort A and 16 months in cohort B.

For the two cohorts taken together, the most common treatment-related adverse events (TREs), regardless of grade, were fatigue (77%), diarrhea (46%), palmar-plantar erythrodysesthesia (32% ) and nausea (31%).

Grade 3-4 ATEs occurred in 15 patients, the most common being fatigue (7%) and mucositis (5%). There were no neurological toxic effects – such as seizures, cerebral hemorrhage, or stroke – and no treatment-related deaths.

“In the absence of consensus guidelines and prospective data, this international retrospective experience provides evidence that cabozantinib can generally be administered safely and is active in this relatively large population with a poor prognosis,” the researchers wrote. “Support for prospective studies evaluating the efficacy of cabozantinib for brain metastases in patients with RCC is essential. “

Disclosures: Some study authors reported affiliations with biotechnology, pharmaceutical and / or device companies. Please see the original reference for a full list of disclosures.


Hirsch L, Chanza NM, Farah S, et al. Clinical activity and safety of cabozantinib for brain metastases in patients with renal cell carcinoma. JAMA Oncol. Published online October 21, 2021. doi: 10.1001 / jamaoncol.2021.4544.

This article originally appeared on Cancer Therapy Advisor


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