Are erlotinib and gefitinib interchangeable, opposite or complementary for non-small cell lung cancer treatment? Biological, pharmacological and clinical aspects

Crit Rev Oncol Hematol. 2014 Feb;89(2):300-13. doi: 10.1016/j.critrevonc.2013.08.003. Epub 2013 Aug 28.

Abstract

Gefitinib and erlotinib are the two anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) approved for treatment of advanced NSCLC patients. These drugs target one of the most important pathways in lung carcinogenesis and are able to exploit the phenomenon of 'oncogene addiction', with different efficacy according to EGFR gene mutational status in tumor samples. Gefitinib has been approved only for EGFR mutation bearing patients regardless the line of treatment, while erlotinib is also indicated in patients without EGFR mutation who undergo second- or third-line treatment. Some studies evaluated the main differences between these drugs both for direct comparison and to improve their sequential use. In particular, toxicity profile resulted partially different, and these observations may be explained by several molecular and pharmacokinetic features. Therefore, this review integrates preclinical data with clinical evidences of TKIs to guide the optimization of currently available treatments in advanced NSCLC patients.

Keywords: EGFR; Erlotinib; Gefitinib; Lung cancer; NSCLC; Tyrosine kinase.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • Erlotinib Hydrochloride
  • Gefitinib
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / therapeutic use*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • Erlotinib Hydrochloride
  • ErbB Receptors
  • Gefitinib