Epidermal Growth Factor Receptor Mutated Advanced Non-Small Cell Lung Cancer: A Changing Treatment Paradigm

Hematol Oncol Clin North Am. 2017 Feb;31(1):83-99. doi: 10.1016/j.hoc.2016.08.003.

Abstract

Activating mutations in the epidermal growth factor receptor (EGFR) are present in approximately 15% of US patients with lung adenocarcinoma. EGFR tyrosine kinase inhibitors are associated with high response rate and progression-free survival for patients with non-small cell lung cancer with this genotype. Gefitinib, erlotinib, and afatinib are the EGFR tyrosine kinase inhibitors that are presently in clinical use. Understanding resistance mechanisms has led to the identification of a secondary mutational target, T790M, in more than half of patients, for which osimertinib has been approved. This article reviews the current treatments, resistance mechanisms, and strategies to overcome resistance.

Keywords: Afatinib; Epidermal growth factor receptor (EGFR); Erlotinib; Gefitinib; Non–small cell lung cancer; Osimertinib; TKI resistance; Tyrosine kinase inhibitors (TKI).

Publication types

  • Review

MeSH terms

  • Acrylamides
  • Adenocarcinoma* / drug therapy
  • Adenocarcinoma* / enzymology
  • Adenocarcinoma* / genetics
  • Afatinib
  • Amino Acid Substitution
  • Aniline Compounds
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / enzymology
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • ErbB Receptors* / antagonists & inhibitors
  • ErbB Receptors* / genetics
  • Erlotinib Hydrochloride / therapeutic use
  • Gefitinib
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / enzymology
  • Lung Neoplasms* / genetics
  • Mutation, Missense*
  • Piperazines / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use*
  • Quinazolines / therapeutic use

Substances

  • Acrylamides
  • Aniline Compounds
  • Piperazines
  • Protein Kinase Inhibitors
  • Quinazolines
  • osimertinib
  • Afatinib
  • Erlotinib Hydrochloride
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib