Optimizing treatment of renal cell carcinoma with VEGFR-TKIs: a comparison of clinical pharmacology and drug-drug interactions of anti-angiogenic drugs

•Anti-angiogenic treatment is an important option that has changed the therapeutic landscape in cancer patients, particularly those with renal cell carcinoma.•VEGFR-TKIs show clear differences regarding their selectivity, potency, pharmacokinetics and metabolism.•Tivozanib and axitinib are the most potent inhibitors of VEGFR1, 2 and 3, tivozanib being the VEGFR-TKI characterized by the highest bioavailability.•Drug-drug interactions may significantly alter the pharmacokinetic profile of selected VEGFR-TKI inhibitors thus influencing their safety profile.•Knowledge of key pharmacokinetic and pharmacodynamic differences may increase the safety and efficacy of use of VEGFR-TKI. Anti-angiogenic treatment is an important option that has changed the therapeutic landscape in various tumors, particularly in patients affected by renal cell carcinoma (RCC). Agents that block signaling pathways governing tumor angiogenesis have raised high expectations among clinicians. Vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) comprise a heterogeneous class of drugs with distinct pharmacological profiles, including potency, selectivity, pharmacokinetics and drug-drug interactions. Among them, tivozanib is one of the last TKIs introduced in the clinical practice; this drug selectively targets VEGFRs, it is characterized by a favorable pharmacokinetics and safety profile and has been approved as first-line treatment for patients with metastatic RCC (mRCC). In this article, we describe the clinical pharmacology of selected VEGFR-TKIs used for the treatment of mRCC, highlighting the relevant differences; moreover we aim to define the main pharmacologic characteristics of these drug.