Cabozantinib in the treatment of advanced renal cell carcinoma: design, development, and potential place in the therapy

Paolo Grassi, Elena Verzoni, Raffaele Ratta, Alessia Mennitto, Filippo de Braud, Giuseppe Procopio Department of Medical Oncology, Genitourinary Cancer Unit, Fondazione IRCCS Istituto nazionale Tumori, Milan, Italy Abstract: The treatment of metastatic renal cell carcinoma (mRCC) has markedly improved over the last few years with the introduction of several targeted agents in clinical practice. Nevertheless, either primary or secondary resistance to inhibition of VEGF and mTOR pathways has limited the clinical benefit of these systemic treatments. Recently, a better understanding of the involvement of MET and its ligand HGF in many biological processes made this signaling pathway an attractive therapeutic target in oncology, particularly in mRCC. Herein, we review the development of cabozantinib, a recently approved inhibitor of multiple tyrosine kinase receptors, including MET, VEGFRs, and AXL, which has proven to increase progression-free survival and overall survival when compared to everolimus in mRCC patients who had progressed after VEGFR-targeted therapy. Finally, we discuss the potential role of cabozantinib within the current treatment landscape for mRCC. Keywords: cabozantinib, XL-184, metastatic renal cell carcinoma, VEGF-inhibitor, c-Met, targeted therap