Cabozantinib produced intracranial and extracranial responses in patients with renal cell carcinoma (RCC) and 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 patients’ median age at cabozantinib initiation was 61 years (range, 34-81 years), and most were men (78%).

The patients were divided into cohorts A and B. Cohort A included 33 patients who had evidence of intracranial progression without concomitant brain-directed local 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 included 55 patients, 35 who had evidence of progression with concomitant brain-directed local therapy and 20 who had stable intracranial disease at the start of cabozantinib treatment. Concomitant therapy consisted of stereotactic radiosurgery (n=26), whole-brain radiotherapy (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 PRs).

The extracranial response rate was 48% in cohort A (16 PRs) and 38% in cohort B (1 CR and 24 PRs). 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 both cohorts together, the most common treatment-related adverse events (TEAEs) of any grade were fatigue (77%), diarrhea (46%), palmar-plantar erythrodysesthesia (32%), and nausea (31%).

Grade 3-4 TEAEs occurred in 15 patients, the most frequent being fatigue (7%) and mucositis (5%). There were no neurological toxic effects — such as seizure, brain 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 generally can be administered safely and is active in this relatively large population with poor prognosis,” the researchers wrote. “Support of prospective studies evaluating the efficacy of cabozantinib for brain metastases in patients with RCC is critical.”

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

Reference

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.