EGFR C797S as a Resistance Mechanism of Lazertinib in Non-small Cell Lung Cancer with EGFR T790M Mutation

Cancer Res Treat. 2020 Oct;52(4):1288-1290. doi: 10.4143/crt.2020.278. Epub 2020 Jun 22.

Abstract

The non-small cell lung cancer with activating epidermal growth factor receptor (EGFR) mutation eventually acquires resistant to either first or second-generation EGFR tyrosine kinase inhibitor (TKI). As the following option, targeting EGFR T790M with third-generation EGFR TKI is now established as a standard treatment option. In this study, we are reporting the first case of resistance mechanism to the novel third-generation EGFR TKI, lazertinib, which showed promising clinical efficacy in phase 1-2 study. The patients showed resistance to the treatment by acquiring the additional EGFR C797S mutation in cis which is also confirmed from the patient-derived cell lines.

Keywords: ErbB receptors; Lazertinib; Non-small cell lung cancer; Third-generation EGFR tyrosine kinase inhibitor.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • DNA Mutational Analysis
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Morpholines / pharmacology*
  • Morpholines / therapeutic use
  • Mutation
  • Pyrazoles / pharmacology*
  • Pyrazoles / therapeutic use
  • Pyrimidines / pharmacology*
  • Pyrimidines / therapeutic use

Substances

  • Morpholines
  • Pyrazoles
  • Pyrimidines
  • lazertinib
  • EGFR protein, human
  • ErbB Receptors