Cabozantinib is associated with an intracranial response in the treatment of brain metastases from renal cell carcinoma

1. Intracranial response rate of 55% was reported in patients receiving cabozantinib with progressing brain metastases with no concomitant brain-directed local therapy

2. Cabozantinib was well-tolerated with common adverse events such as fatigue, diarrhea and palmar-plantar erythrodysesthesia

Evidence Rating Level: 2 (Good)

Study Rundown: Patients with metastatic renal cell carcinoma (RCC) may develop brain metastases, increasing their morbidity and mortality. Currently, the standard treatment of care includes local therapies targeting metastases (e.g., stereotactic radiosurgery, whole-brain radiotherapy). RCC patients with brain metastases were poorly represented in other clinical trials and the aim of this study was to characterize cabozantinib monotherapy in the treatment of progressive brain metastases. This study aimed to evaluate the efficacy and safety of cabozantinib for the treatment of brain metastases in patients with metastatic RCC. Patients were divided into two cohorts. Cohort A comprised of patients with progressing brain metastases who did not receive brain-directed local therapy concomitantly. Cohort B comprised of patients with stable brain metastases who received brain-directed local therapy concomitantly. Cabozantinib showed a notable intracranial response rate of 55% and 47% in cohorts A and B, respectively. Commonly reported adverse events included fatigue, diarrhea and palmar-plantar erythrodysesthesia. Limitations to the study include having a low number of patients in each cohort and the lack of information regarding other concomitant medications that the patients may be on, which could influence the safety profile of cabozantinib. Overall, this study demonstrated that cabozantinib could be an effective treatment for patients with brain metastases from RCC, particularly patients with progressive brain metastases. However, further investigation is required to confirm the findings and establish a more comprehensive efficacy and safety profile of cabozantinib in patients with brain metastases, including in combination with other therapies.

Click to read the study in JAMA Oncology

Relevant Reading: Cabozantinib in Renal Cell Carcinoma With Brain Metastases: Safety and Efficacy in a Real-World Population

In-Depth [retrospective cohort]: This was a multicenter, international, retrospective cohort study of 88 patients at 15 academic centers in the United States, Belgium, France, and Spain. Patients were eligible if they had brain metastases from RCC and received cabozantinib between January 2014 and October 2020. The patients were divided into 2 cohorts. Cohort A included patients with progressing brain metastases at the start of cabozantinib who were not receiving concomitant brain-directed local therapy. Cohort B included patients with stable brain metastases at the start of cabozantinib who were receiving brain-directed local therapy concomitantly. The study examined the intracranial and extracranial objective response rates (ORRs) as well as the safety profile of cabozantinib. The intracranial ORR for Cohort A and B were 55% (95% confidence interval [CI]: 36%-73%) and 47% (95% CI: 33%-61%), respectively. 32% of the patients in Cohort A experienced stable disease compared to 42% of patients in Cohort B. 13% of the patients in Cohort A and 11% of patients in Cohort B experienced progressive disease. The extracranial ORR for Cohort A and B were 48% (95% CI: 31%-66%) and 38% (95% CI: 25%-52%), respectively. The median overall survival was 16.0 months (95%CI, 12.0-21.9months). Commonly reported adverse events included fatigue (77%), diarrhea (46%) and palmar-plantar erythrodysesthesia (32%). There were no reported deaths and neurological toxic effects (e.g., seizure, brain hemorrhage, stroke).

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