Second-generation epidermal growth factor receptor tyrosine kinase inhibitors in lung cancers

J Natl Compr Canc Netw. 2013 Feb 1;11(2):161-9. doi: 10.6004/jnccn.2013.0024.


EGFR mutations identify patients who are more likely to respond to treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) than cytotoxic chemotherapy. The distinct success of the first-generation EGFR TKIs erlotinib and gefitinib has been accompanied by the observation that acquired resistance to these treatments develops after a median of 1 year of treatment. Newer, second-generation EGFR TKIs have been developed with the intent to delay or overcome acquired resistance by the broader inhibition of kinases (eg, HER2 and vascular endothelial growth factor receptor) and/or altering the interactions with EGFR through irreversibly binding to the kinase domain. This article discusses many of these agents (including afatinib, dacomitinib, XL647, AP26113, and CO-1686) which have the potential for greater efficacy compared with first-generation EGFR TKIs, and may also have clinical activity against other oncogenic mutations within the EGFR family, including HER2.

Trial registration: NCT01449461.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / ethnology*
  • Lung Neoplasms / genetics
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use*
  • Randomized Controlled Trials as Topic


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • ErbB Receptors

Associated data