Cabozantinib study shows high intracranial activity in kidney cancer

The multikinase inhibitor cabozantinib (Cabometyx) demonstrated a strong intracranial response rate in patients with metastatic renal cell carcinoma (RCC) and brain metastases, according to findings from a retrospective analysis published in JAMA Oncology.1,2

At a median follow-up of 17 months (range, 2-74 months), the intracranial response rate was 55% in a cohort of patients with RCC and progressing brain metastases without concomitant brain-directed local therapy. In a separate cohort of patients with RCC and stable or progressing brain metastases concomitantly treated by brain-directed local therapy, the intracranial response rate was 47%.

“In this cohort study, cabozantinib showed considerable intracranial activity and an acceptable safety profile in patients with RCC and brain metastases. Support of prospective studies evaluating the efficacy of cabozantinib for brain metastases in patients with RCC is critical,” the authors wrote in their study conclusion.

Overall, the retrospective cohort study included 88 patients with metastatic RCC and brain metastases who received single-agent cabozantinib during any line of treatment. Patient had been treated between January 2014 and October 2020 at 15 clinical sites in the United States, Belgium, France, and Spain.

Study cohort A included 33 (38%) patients without concomitant brain-directed local therapy and cohort B included 55 (62%) patients with stable or progressing brain metastases concomitantly treated by brain-directed local therapy. Over three-fourths (78%) of patients were male, and the median age at the start of cabozantinib treatment was 61 years (range, 34-81).

Cohort A had an intracranial response rate of 55% and extracranial response rate of 48%. The median time to treatment failure was 8.9 months and the median overall survival (OS) was 15 months. For cohort B, the intracranial and extracranial response rates were 47% and 38%, respectively. The median time to treatment failure was 9.7 months and the median OS was 16 months.

“We measured the dimension of the metastases in the brain and saw a response rate that was higher than what we usually expect, and there were some nice examples of metastases really shrinking,” senior study author Toni Choueiri, MD, director of the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute, stated in a news release. The news release also noted, however, that Choueiri cautioned that not all of the responses were durable, with some tumors becoming resistant several months later.

Regarding safety, the investigators considered cabozantinib to be well tolerated. There were no unexpected safety signals or neurological adverse events observed. There were also no treatment-related deaths.

To validate these retrospective findings, the ongoing, prospective, multicenter, phase 2 CABRAMETtrial (NCT03967522) is evaluating the safety and efficacy of cabozantinib in patients with metastatic RCC who have brain metastases.

“Hopefully this will be definitive,” Choueiri stated in the release.

Cabozantinib was approved by the FDA in December 2017 as a treatment for previously untreated patients with advanced RCC. Most recently, in January 2021, the FDA approved the combination of nivolumab (Opdivo) plus cabozantinib for the frontline treatment of patients with advanced RCC.

References

1. Targeted drug shows activity against brain metastases in kidney cancer. Published online October 21, 2021. Accessed November 2, 2021. https://bit.ly/3CEIYhT.

2. Hirsch L, Martinez Chanza N, Farah S, et al. Clinical activity and safety of cabozantinib for brain metastases in patients with renal cell carcinoma [published online ahead of print October 21, 2021]. JAMA Oncol. doi: 10.1001/jamaoncol.2021.4544