[Cabozantinib: Mechanism of action, efficacy and indications].

Abstract

Cabozantinib is an oral multiple tyrosine kinase receptor inhibitor (ITK): VEGFR2, c-MET and RET. Inhibition of VEGFR and c-MET decrease resistance of VEGFR inhibitor via c-MET axis. Cabozantinib improve progression-free survival (PFS) in progressive metastatic medullary thyroid cancer (MTC): 4 months in the placebo group and 11.2 months in the cabozantinib group (P<0.001) in all patient subgroups including those with or without prior ITK and RET mutation status. Cabozantinib increased overall survival (OS) compared with everolimus in patients with advanced renal cell carcinoma who progressed after previous VEGFR ITK treatment: 21.4 months in cabozantinib group and 16.5 months in everolimus group (P<0.0003). Cabozantinib obtained the AMM for the treatment of progressive metastatic MTC and advanced renal cell carcinoma. Cabozantinib is a new option in the treatment of MTC by inclusion in therapeutic trials (no payment in this indication) and advanced renal cell carcinoma (hospital delivery). Its tolerance is similar to anti-angiogenic therapies and justifies an optimal management of the secondary effect.

• Authors: Valérie Cochin, Marine Gross-Goupil, Alain Ravaud, Yann Godbert, Sylvestre Le Moulec
• Journal: Bulletin du cancer (Bull Cancer) Vol. 104 Issue 5 Pg. 393-401 (May 2017) ISSN: 1769-6917 [Electronic] France
• Vernacular Title: Cabozantinib : modalités d’action, efficacité et indications.
• PMID: 28477875 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Chemical References

• Anilides
• Antineoplastic Agents
• Piperidines
• Pyridines
• Quinazolines
• cabozantinib
• Everolimus
• KDR protein, human
• Proto-Oncogene Proteins c-ret
• RON protein
• Receptor Protein-Tyrosine Kinases
• Vascular Endothelial Growth Factor Receptor-2
• vandetanib

Topics

• Anilides (pharmacology, therapeutic use)
• Antineoplastic Agents (pharmacology, therapeutic use)
• Bone Neoplasms (drug therapy, secondary)
• Carcinoma, Neuroendocrine (drug therapy, genetics)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Carcinoma, Renal Cell (drug therapy, mortality)
• Clinical Trials as Topic
• Disease-Free Survival
• Everolimus (therapeutic use)
• Humans
• Kidney Neoplasms (drug therapy, mortality)
• Lung Neoplasms (drug therapy)
• Male
• Piperidines (pharmacology)
• Prostatic Neoplasms (drug therapy)
• Proto-Oncogene Proteins c-ret (antagonists & inhibitors, genetics)
• Pyridines (pharmacology, therapeutic use)
• Quinazolines (pharmacology)
• Receptor Protein-Tyrosine Kinases (antagonists & inhibitors, pharmacology, therapeutic use)
• Thyroid Neoplasms (drug therapy, genetics)
• Vascular Endothelial Growth Factor Receptor-2 (antagonists & inhibitors)