Cabozantinib yields promising intracranial activity with an acceptable safety profile for patients who developed brain metastases from renal cell carcinoma (RCC), according to study results published in JAMA Oncology.
While approximately 10% to 15% of patients with metastatic RCC harbor brain metastases, most data on potential treatments for these patients are derived from retrospective studies and prospective single-arm studies. The objective of the current study was to explore 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 between January 2014 and October 2020 in 15 institutions. All patients had ≥1 follow-up imaging evaluation of the brain.
Patients were classified into 2 cohorts: cohort A included patients with progressing brain metastases at cabozantinib initiation and without concomitant brain-directed local therapy within the past 2 months, including stereotactic radiosurgery, whole-brain radiotherapy, and surgery; cohort B included patients with stable brain metastases at cabozantinib initiation or patients with progressing brain metastases concomitantly treated by brain-directed local therapy.
The primary end point was intracranial radiological response rate determined by modified Response Evaluation Criteria in Solid Tumors, version 1.1, and time to brain progression and time to treatment failure were determined.
The study sample included 88 patients (69 men; mean age, 61 years) treated with cabozantinib for RCC with brain metastases, including 33 patients in cohort A and 55 patients in cohort B.
The median follow-up time after cabozantinib initiation 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 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 median overall survival was 16 months (95% CI, 12.0-21.9 months).
Cabozantinib was well tolerated, with no unexpected toxic effects or neurological adverse events, and no treatment-related deaths.
The study had several limitations, including the retrospective design, lack of central radiological review on all cases, and missing information regarding use of systemic corticosteroids.
“These findings show considerable intracranial activity and an acceptable safety profile of cabozantinib in patients with renal cell carcinoma and brain metastases,” concluded the researchers.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Hirsch L, Martinez Chanza N, Farah S, et al. Clinical activity and safety of cabozantinib for brain metastases in patients with renal cell carcinoma. JAMA Oncol. Published online October 21, 2021. doi: 10.1001/jamaoncol.2021.4544