Cabozantinib for the treatment of renal cell carcinoma.
Agents that target the vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) pathway as well as the PD-1 checkpoint inhibitor nivolumab are standard therapies for advanced renal cell carcinoma (RCC). Recently, cabozantinib, an inhibitor of MET, VEGF receptors, and AXL, was approved by the FDA and European Commission based on improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared to standard of care treatment with everolimus in a randomized phase 3 trial in advanced RCC after prior VEGFR-tyrosine kinase inhibitor (TKI) therapy. Areas covered:The preclinical development and scientific rationale, pharmacokinetics, and clinical efficacy and safety of cabozantinib for the treatment of advanced RCC are reviewed. The use of cabozantinib in clinical practice with the growing number of available treatments for advanced RCC is discussed. Expert opinion: Cabozantinib is the only therapy for advanced RCC that has improved PFS, ORR, and OS in a pivotal phase 3 trial after prior antiangiogenic therapy. While no clinical trials have been published comparing cabozantinib with another TKI, available clinical data suggest it could be the most efficacious TKI for second-line therapy. Preliminary encouraging results have also been reported in a phase 2 trial in untreated poor- and intermediate- risk patients with RCC, indicating that treatment with cabozantinib may also be beneficial in the first-line setting.
a Department of Medical Oncology , Gustave Roussy , Villejuif , France.
Bernard
B
Escudier
b Department of Medical Oncology , Exelixis, Inc. , South San Francisco , California.
Julie C
JC
Lougheed
a Department of Medical Oncology , Gustave Roussy , Villejuif , France.
Laurence
L
Albiges
D000813:Anilides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D000068338:Everolimus / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D000077594:Nivolumab; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
D000813:Anilides; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C558660:cabozantinib; D000077594:Nivolumab; D000068338:Everolimus; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D058570:TOR Serine-Threonine Kinases
Cabozantinib; METEOR; TKI; VEGFR; renal cell carcinoma