Control of renal cell carcinoma brain metastases with cabozantinib following progression on immune checkpoint inhibitor therapy

Patients with metastatic renal cell carcinoma are often affected by metastases to the brain that result in significant complications as well as limitations in clinical trial participation. Early generation tyrosine-kinase inhibitor and immune checkpoint inhibitor therapies along with combinatorial regimens have provided superior responses of extracranial disease control in metastatic renal cell carcinoma. However, these agents perform poorly at controlling intracranial disease. Cabozantinib is a small molecule tyrosine-kinase inhibitor that targets multiple tyrosine kinases including VEGFR2, MET, RET, as well as c-KIT, AXL, and FLT3. These kinases function critically for tumor growth, angiogenesis, survival and metastasis in a multitude of tumor types. Cabozantinib effectively crosses the blood-brain barrier and has shown clinical and radiographic responses in other cancers of the central nervous system, including recurrent glioma and metastatic non-small cell lung cancers. The case reported here describes the use and efficacy of cabozantinib for uncontrolled brain metastases that failed prior tyrosine-kinase inhibitor and checkpoint inhibitor therapy. Cabozantinib resulted in decreased size and number of intracranial metastases and was continued with checkpoint inhibitor therapy for extracranial disease control. This case illustrates the clinical benefit of cabozantinib in controlling renal cell carcinoma brain metastases in patients with excellent extracranial disease control.