Axitinib for the treatment of advanced non-small-cell lung cancer

Expert Opin Investig Drugs. 2013 Jun;22(6):765-73. doi: 10.1517/13543784.2013.775243. Epub 2013 Mar 1.

Abstract

Introduction: Lung cancer is the most frequently diagnosed cancer in men and comprises 23% of total cancer deaths worldwide. The majority of patients present with advanced disease, for whom the 5-year survival is < 5%. Since angiogenesis plays a central role in tumourigenesis, inhibiting this pathway may improve outcomes in non-small-cell lung cancer (NSCLC). Axitinib is one of the latest and most potent anti-angiogenic tyrosine kinase inhibitors (TKI) currently being evaluated to treat NSCLC.

Areas covered: In this review, the rationale for targeting angiogenesis in lung cancer, other angiogenic agents in NSCLC, axitinib's mechanism of action, pharmacology and metabolism, and the preclinical and clinical data to date in NSCLC will be discussed.

Expert opinion: Several TKI which target angiogenesis pathways have resulted in improved response rates and progression-free survival in NSCLC, but no improvement in overall survival in clinical trials. Axitinib is a more potent inhibitor of vascular endothelial growth factor receptors than other TKI, but this has yet to translate into a clinical benefit. Phase II trials are ongoing, but the published data to date has yet to support a role for axitinib in the treatment algorithm for NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / pharmacology
  • Animals
  • Axitinib
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / epidemiology
  • Disease-Free Survival
  • Humans
  • Imidazoles / pharmacology*
  • Indazoles / pharmacology*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / epidemiology
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / pharmacology
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Survival Rate

Substances

  • Angiogenesis Inhibitors
  • Imidazoles
  • Indazoles
  • Protein Kinase Inhibitors
  • Axitinib
  • Protein-Tyrosine Kinases