Cabozantinib shows activity against RCC brain metastases
medwireNews: Cabozantinib has “considerable” intracranial activity in patients with advanced renal cell carcinoma (RCC) and brain metastases, say the authors of a chart review published in JAMA Oncology.
The study included data on 88 patients who received single-agent cabozantinib – primarily in the third or later line (68%) – at one of 15 academic centers in the USA, Belgium, France, or Spain between January 2014 and October 2020. Participants were aged a median of 61 years at the time of cabozantinib initiation and the majority (78%) were men.
Among the 33 participants with progressing brain metastases who were not receiving concomitant brain-directed local therapy, cabozantinib monotherapy achieved an intracranial objective response rate (ORR) of 55%, including three complete and 14 partial responses.
The extracranial ORR was 48%, while the median time to treatment failure was 8.9 months and median overall survival (OS) was 15.0 months.
The remaining 55 patients, who either had stable metastases or progressing metastases concomitantly treated with brain-directed local therapy, also had similarly favorable outcomes with cabozantinib treatment.
The intracranial ORR in this group was 47%, with one complete and 24 partial responses, and the extracranial ORR was 38%. The median time to treatment failure was 9.7 months and median OS was 16.0 months.
Across both cohorts, “cabozantinib demonstrated a safety profile consistent with previous pivotal studies in a healthier population of patients,” report Toni Choueiri (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) and collaborators.
In all, 17% of the 88 participants experienced a treatment-related adverse event of grade 3 or 4, most commonly fatigue (7%) and mucositis (5%). Just over half (55%) of the patients required a dose reduction and 11% discontinued cabozantinib permanently due to toxicities, but there were 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,” say the researchers.
And they conclude: “Further investigations are needed to confirm the present findings and to extend evaluation to more symptomatic or aggressive cases not included in this study.
“Support of studies such as the ongoing French phase 2 CABRAMET study, which is evaluating prospectively the efficacy of cabozantinib on brain metastases in patients with RCC, is critical.”
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