Cabozantinib shows promising intracranial activity with an acceptable safety profile for patients who developed brain metastasis from renal cell carcinoma (RCC), according to study results published in JAMA Oncology.
While approximately 10 to 15% of patients with metastatic RCC have brain metastases, most of the data on possible treatments for these patients comes from retrospective studies and prospective one-arm studies. The aim of the current study was to evaluate the safety and efficacy of cabozantinib in patients with RCC and brain metastases.
The multicenter, international, retrospective cohort study included patients with histologically proven brain metastases from RCC who were treated in 15 facilities between January 2014 and October 2020. All patients had ≥ 1 follow-up brain imaging.
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The patients were divided into 2 cohorts: Cohort A comprised patients with progressive brain metastases at the beginning of cabozantinib and without concomitant brain-directed local therapy within the last 2 months, including stereotactic radiosurgery, whole-brain radiation and surgery; Cohort B comprised patients with stable brain metastases at the beginning of cabozantinib or patients with progressive brain metastases who were simultaneously treated with brain-directed local therapy.
The primary endpoint was the intracranial radiographic response rate as determined by the Modified Response Evaluation Criteria in Solid Tumors Version 1.1, and the time to brain progression and time to treatment failure were determined.
The study sample comprised 88 patients (69 men; mean age 61 years) who were treated with cabozantinib for RCC with brain metastases, including 33 patients in cohort A and 55 patients in cohort B.
The median follow-up after starting cabozantinib treatment was 17 months (range, 2–74 months).
In Cohort A, the objective intracranial response rate was 55% (95% CI, 36–73%), including 3 (10%) complete responses and 14 (45%) partial responses. The extracranial response rate was 48% (95% CI, 31-66%) with no complete response and 16 partial responses. The median time to treatment failure was 8.9 months (95% CI: 5.9-12.3 months) and the median overall survival was 15 months (95% CI, 9.0-30.0 months).
In Cohort B, the intracranial response rate was 47% (95% CI, 33–61%), including 1 complete response (2%) and 24 partial responses (45%). The extracranial response rate was 38% (95% CI, 25–52%), with 1 complete response and 24 partial responses. The median time to treatment failure was 9.7 months (95% CI, 6.0–13.2 months) and the median overall survival was 16 months (95% CI, 12.0–21.9 months).
Cabozantinib was well tolerated with no unexpected toxic or neurological side effects and no treatment-related deaths.
The study had several limitations, including retrospective design, the lack of a central radiological review of all cases, and a lack of information on systemic corticosteroid use.
“These results show significant intracranial activity and an acceptable safety profile for cabozantinib in patients with renal cell carcinoma and brain metastases,” the researchers concluded.
Disclosure: Some study authors stated links with biotech, pharmaceutical, and / or device companies. For a full list of author disclosures, see the original reference.
reference
L. Hirsch, N. Martinez Chanza, S. Farah et al. Clinical activity and safety of cabozantinib in brain metastasis in patients with renal cell carcinoma. JAMA Oncol. Published online October 21, 2021. doi: 10.1001 / jamaoncol.2021.4544
