In a retrospective cohort study reported in JAMA Oncology, Hirsch et al found that cabozantinib showed substantial activity in treating brain metastases in patients with renal cell carcinoma.

As stated by the investigators, “Patients with brain metastases from renal cell carcinoma have been underrepresented in clinical trials, and effective systemic therapy is lacking. Cabozantinib shows robust clinical activity in metastatic renal cell carcinoma, but its effect on brain metastases remains unclear.”

Study Details

The study involved data from 88 patients with metastatic renal cell carcinoma and brain metastases treated with cabozantinib in 15 institutions in the United States, Belgium, France, and Spain between January 2014 and October 2020. Cabozantinib was mostly administered as second-line treatment (n = 24, 27%) or third-line or beyond treatment (n = 60, 68%). Patients were categorized as having progressing brain metastases without concomitant brain-directed local therapy (cohort A, n = 33) or stable or progressing brain metastases concomitantly treated with brain-directed local therapy (n = 55). Intracranial response rate was assessed by modified Response Evaluation Criteria in Solid Tumors version 1.1.

Key Findings

Median follow-up was 17 months (range = 2–74 months).

Among 31 evaluable patients in cohort A, intracranial response was observed in 17 (55%, 95% confidence interval [CI] = 36%–73%), with complete response seen in 3 (10%). An additional 32% of patients had stable disease. Intracranial progression at 6 months was 25% (95% CI = 11%–41%). Extracranial response was achieved in 48% (95% CI = 31%–66%) of all patients. Median time to treatment failure was 8.9 months (95% CI = 5.9–12.3 months) and median overall survival was 15 months (95% CI = 9.0–30.0 months).

In cohort B, intracranial response was observed in 25 (47%, 95% CI = 33%–61%) of 53 evaluable patients, with complete response in 1 (2%). An additional 42% of patients had stable disease. Intracranial progression at 6 months was 15% (95% CI = 7%–25%). Extracranial response was achieved in 38% (95% CI = 25%–52%) of all patients. Median time to treatment failure was 9.7 months (95% CI = 6.0–13.2 months) and median overall survival was 16 months (95% CI = 12.0–21.9 months).

Among all patients, the most common treatment-related adverse events of any grade were fatigue (77%), diarrhea (46%), palmar-plantar erythrodysesthesia (32%), and nausea (31%); grade 3 or 4 events occurred in 17%, most commonly fatigue (7%) and mucositis (5%). No neurologic adverse events were reported. Adverse events led to discontinuation in 11%. No treatment-related deaths were observed.

The investigators concluded, “In this cohort study, cabozantinib showed considerable intracranial activity and an acceptable safety profile in patients with renal cell carcinoma and brain metastases. Support of prospective studies evaluating the efficacy of cabozantinib for brain metastases in patients with renal cell carcinoma is critical.”

Toni K. Choueiri, MD, of the Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, is the corresponding author for the JAMA Oncology article.

Disclosure: For full disclosures of the study authors, visit jamanetwork.com.