Tyrosine Kinase and Mammalian Target of Rapamycin Inhibitors in the Treatment of Advanced Renal Cell Carcinoma: Practical Clinical Implications of Pharmacologic Features

Abstract

The development of multiple vascular endothelial growth factor- and mammalian target of rapamycin-targeted therapies in advanced renal cell carcinoma has resulted in significant clinical benefit. However, the availability of multiple treatment options has led to a more complicated clinical decision-making process. Prognostic factors have been incorporated into the inclusion criteria for pivotal clinical trials and have thus provided some guidance regarding the selection and sequencing of therapy. Even within a given patient risk group and particular line of therapy, questions remain regarding the optimal choice of a targeted agent. The present review provides a practical, clinician-oriented assessment of pharmacologic factors that should be considered when a receptor tyrosine kinase or mammalian target of rapamycin kinase inhibitor is used to treat patients with advanced or metastatic renal cell carcinoma. Although these 2 classes of agents have different mechanisms of action, they are metabolized by similar pathways, resulting in broadly similar pharmacokinetic and drug-drug interaction profiles. To further individualize therapy and optimize clinical benefit, an enhanced understanding of the key pharmacologic features that differentiate these agents is important.

Keywords: Decision-making; Kidney cancer; Management; Pharmacology; Targeted therapy.