Impact of tivozanib on patient outcomes in treatment of advanced renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common type of kidney malignancy, and the clear-cell subtype represents the majority of RCCs. RCC is a heterogeneous disease in terms of genetic and histological features which determine the behavior of the disease. The () is a tumor suppressor gene and mutations of this gene are seen in 95% of clear-cell RCCs. Inactivation of  causes the accumulation of hypoxia-inducible factor-1 (HIF-1), and in turn, accumulation of HIF-1 induces overexpression of vascular endothelial growth factor (VEGF); the increase in VEGF expression makes RCC a highly vascularized tumor, and forms the rationale for antiVEGF treatment. In the past decade, improvement in the survival of RCC patients has been observed due to new effective therapies, such as antiVEGF and mammalian target of rapamycin (mTOR) targeting agents and immune checkpoint inhibitors. The majority of VEGF targeted agents are not just selective to VEGF receptors, but usually also have inhibitory effects on other kinases, such as c-KIT and FLT3. Tivozanib is an extremely potent and selective tyrosine kinase inhibitor (TKI) of VEGFR-1, 2, and 3, with a relatively long half-life, that is approved by the European Commission for the treatment of advanced/metastatic RCC. Tivozanib, at very low serum concentration can inhibit phosphorylation of VEGFR -1, -2, and -3 tyrosine kinase activity. This article summarizes the clinical data on tivozanib in the treatment of advanced/metastatic RCC.