Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer

J Hematol Oncol. 2016 Apr 12:9:34. doi: 10.1186/s13045-016-0268-z.

Abstract

The tyrosine kinase inhibitors (TKI) against epidermal growth factor receptor (EGFR) are widely used in patients with non-small cell lung cancer (NSCLC). However, EGFR T790M mutation leads to resistance to most clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation have been in active clinical development. These agents include osimertinib, rociletinib, HM61713, ASP8273, EGF816, and PF-06747775. Osimertinib and rociletinib have shown clinical efficacy in phase I/II trials in patients who had acquired resistance to first- or second-generation TKIs. Osimertinib (AZD9291, TAGRISSO) was recently approved by FDA for metastatic EGFR T790M mutation-positive NSCLC. HM61713, ASP8237, EGF816, and PF-06747775 are still in early clinical development. This article reviews the emerging data regarding third-generation agents against EGFR T790M mutation in the treatment of patients with advanced NSCLC.

Publication types

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

MeSH terms

  • Acrylamides / therapeutic use
  • Aniline Compounds
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Mutation, Missense*
  • Piperazines / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrimidines / therapeutic use

Substances

  • Acrylamides
  • Aniline Compounds
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • osimertinib
  • rociletinib
  • ErbB Receptors