Cabozantinib an Option for Kidney Cancer With Brain Metastases

NEW YORK (Reuters Health) – Cabozantinib showed intracranial activity and an acceptable safety profile in a retrospective study of patients with renal cell carcinoma (RCC) with brain metastases, researchers say.

“The data with cabozantinib are intriguing,” Dr. Toni Choueiri of the Dana-Farber Cancer Institute in Boston told Reuters Health by email. “Because the data are retrospective, I believe surgery +/- radiation should be the primary modality for brain mets.”

“If, overall, the lesions can be captured and stabilized by radiation or resected, you may not need cabozantinib unless it is used ‘anyhow’ for extracranial disease control,” he said. “In case of unsafe location or progression on surgery/radiation, cabozantinib is a reasonable option. There is a prospective study in France (CABRAMET; that is ongoing and will be more definitive.”

As reported in JAMA Oncology, the study included 88 patients with metastatic RCC and brain metastases (78% men; median age at cabozantinib initiation, 61) treated in 15 international institutions between 2014-2020.

Thirty-three patients (38%) with progressing brain metastases without concomitant brain-directed local therapy – defined as stereotactic radiosurgery, whole-brain radiotherapy, and surgery within the last two months before cabozantinib administration – were in cohort A. The rest, with stable or progressing brain metastases concomitantly treated by brain-directed local therapy, were in cohort B.

The median follow-up was 17 months.

The intracranial response rate was 55% in cohort A (including three complete responses and 14 partial responses) and 47% in cohort B (including one complete response and 24 partial responses).

In cohort A, the extracranial response rate was 47%, with no complete responses and 16 partial responses; median time to treatment failure was 8.9 months; and median overall survival was 15 months.

In cohort B, the extracranial response rate was 38%, with one complete response and 24 partial responses; time to treatment failure was 9.7 months; and median overall survival was 16 months.

Cabozantinib was well tolerated, with no unexpected toxic effects or neurological adverse events, nor were any treatment-related deaths reported.

Dr. Yung Lyou, assistant professor in the Department of Medical Oncology and Therapeutics Research at City of Hope in Duarte, California, commented in an email to Reuters Health.

“This was a retrospective study, so it is limited,” he said. “However, the findings are provocative and support the need to further validate these results in a prospective clinical trial.”

“Even when combined with radiation treatment to the brain, it did not appear to cause additional toxic effects in this study,” and therefore should be considered for treatment in this patient population.

Cabozantinib is produced and marketed by Exelixis. Dr. Choueiri and many coauthors have received funds from the company.

SOURCE: JAMA Oncology, online October 21, 2021.

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