Therapeutic approaches for T790M mutation positive non-small-cell lung cancer

Expert Rev Anticancer Ther. 2018 Oct;18(10):1021-1030. doi: 10.1080/14737140.2018.1508347. Epub 2018 Aug 14.

Abstract

Epidermal growth factor receptor (EGFR) mutation positive non-small cell lung cancer (NSCLC) is a subset of lung cancer with demonstrated response to targeted therapies. However, resistance to the first targeted approach usually occurs within the first year, and it is associated in 50-60% of cases to the T790M resistance mutation. Areas covered: The review provides an overview on the significance of the presence of the T790M mutation, its detection, treatment options and subsequent mechanisms of resistance. Expert commentary: Osimertinib is the current treatment option for T790M mutation positive NSCLC after progression to first or second-generation EGFR TKIs, with activity also on brain metastasis. However, the scenario is in continuous evolution and results from clinical trials are awaited in first-line setting and in combination strategies.

Keywords: EGFR; TKI resistance; liquid biopsy; lung cancer; osimertinib.

Publication types

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

MeSH terms

  • Acrylamides
  • Aniline Compounds
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Disease Progression
  • Drug Resistance, Neoplasm
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Molecular Targeted Therapy
  • Mutation
  • Piperazines / pharmacology
  • Protein Kinase Inhibitors / pharmacology

Substances

  • Acrylamides
  • Aniline Compounds
  • Piperazines
  • Protein Kinase Inhibitors
  • osimertinib
  • EGFR protein, human
  • ErbB Receptors