Cabozantinib for the treatment of renal cell carcinoma patients

Abstract

Anti-angiogenesis is a key target of the first-line systemic therapy in renal cell carcinoma. Resistance to this therapy ultimately occurs in almost every patient who requires subsequent treatment to manage disease progression. Cabozantinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor and additionally blocking MET and AXL kinases, which are associated with tumour growth, proliferation, invasion, and resistance. Cabozantinib has been shown to improve overall survival, progression-free survival, and objective response rate in comparison to everolimus in patients with advanced renal cell carcinoma in the phase 3 METEOR study. It resulted in the approval for use in the treatment of advanced renal cell carcinoma following prior vascular endothelial growth factor (VEGF)-targeted therapy and contributed to a change of treatment guidelines, placing cabozantinib among second-line therapy options. Herein we discuss the biological and clinical rationale behind cabozantinib use in renal cell carcinoma therapy and its position in the rapidly developing renal cell carcinoma treatment landscape. We outline current research and future directions for renal cell carcinoma therapy.