Abstract: Clear cell (cc) renal cell carcinoma (RCC) is the most common type of cancer found in the kidney accounting for ~90% of all kidney cancers. In 2012, there were ~337,000 new cases of RCC diagnosed worldwide with an estimated 143,000 deaths, with the highest incidence and mortality in Western countries. Despite improvements in cancer control achieved with VEGF- and mTOR-targeted therapy for RCC, progression remains virtually universal and additional therapies are needed. The pivotal results of the METEOR trial led to cabozantinib’s designation as a breakthrough drug by the US Food and Drug Administration and its approval for treatment of advanced RCC in 2016. Subsequent data from the CABOSUN trial, where caboxantinib is compared with sunitinib, will provide information on the relative activity of cabozantinib as first-line therapy for ccRCC. We review the development of cabozantinib in advanced RCC and its role in the treatment landscape for advanced RCC.


Keywords: cabozantinib, renal cell carcinoma, kidney cancer, clear cell carcinoma, tyrosine kinase inhibitor  


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INTRODUCTION

Clear cell (cc) renal cell carcinoma (RCC) is the most common type of cancer found in the kidney accounting for ~90% of all kidney cancers. In 2012, there were ~337,000 new cases of RCC diagnosed worldwide with an estimated 143,000 deaths, with the highest incidence and mortality in North America and Europe. The USA is among the top four countries in incidence and mortality worldwide.1,2 The development of RCC is associated with smoking, obesity, male sex, and family history and genetic conditions such as von Hippel-Lindau disease as well as possibly type 2 diabetes mellitus and hepatitis C infection.3,4 In the USA, there were an estimated 62,000 new cases and ~14,000 deaths from RCC in 2015.5 Patients with localized disease have a nearly 92% 5-year survival with curative surgery, whereas patients with advanced RCC have 5-year survival rates of ~11%–12%.6 Despite improvements in cancer control achieved with VEGF- and mTOR-targeted therapy for RCC, progression remains virtually universal and additional therapies are needed. In this review, we delineate the differences between cabozantinib and preexisting VEGF-targeted therapy by reviewing the efficacy, safety, and patients who benefit from cabozantinib. We assess the quality of preclinical data and Phases I–III trials testing cabozantinib in various cancer types and identify gaps in knowledge where new trials are needed.