Management of Adverse Events Associated with Cabozantinib Therapy in Renal Cell Carcinoma

Cabozantinib was recently approved for the treatment of advanced renal cell carcinoma (RCC) after treatment with vascular endothelial growth factor (VEGF)-targeted therapy. Cabozantinib is a multikinase inhibitor targeting VEGF receptor (VEGFR) 2, mesenchymal-epithelial transition receptor, and "anexelekto" receptor tyrosine kinase. A 60-mg daily dose led to improved overall survival and progression-free survival (PFS) versus everolimus in advanced RCC patients as a second- or later-line treatment in the METEOR trial. Improved PFS with cabozantinib versus sunitinib has also been demonstrated in the first-line setting in CABOSUN. However, cabozantinib, like other VEGFR inhibitors, is associated with toxicity that may affect the patient's quality of life. The most frequent adverse events (AEs) are diarrhea, fatigue, hypertension, hand-foot syndrome, weight loss, nausea, and stomatitis. This article summarizes the safety profile of cabozantinib in RCC patients and offers guidance for the management of these AEs. We discuss the underlying mechanisms of these AEs and, based on our experiences with cabozantinib and other multikinase inhibitors, we present approaches to manage toxicity. Prophylactic and therapeutic solutions are available to help with the management of toxicity associated with cabozantinib, and adequate interventions can ensure optimum adherence and maximize patient outcomes.