The significance of epidermal growth factor receptor uncommon mutations in non-small cell lung cancer: A systematic review and critical appraisal

Cancer Treat Rev. 2020 Apr:85:101994. doi: 10.1016/j.ctrv.2020.101994. Epub 2020 Feb 21.

Abstract

Uncommon epidermal growth factor receptor (EGFR) mutations collectively account for 10% of EGFR mutations, harboring heterogeneous molecular alterations within exons 18-21 with clinically variable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced Non-Small Cell Lung Cancer (NSCLC) patients. In addition, with the introduction of different NGS gene approach an improvement of EGFR mutations detection was reported. Today, no specific studies have prospectively evaluated uncommon sensitizing mutations in detail and no firm standard of care has been established in the first-line setting. The aim of this comprehensive review is to critically consider the clinical role of uncommon EGFR mutations highlighting the results of several in vitro and in vivo studies, which singly evaluated the sensitivity of uncommon mutations to currently European of Medicines Agency (EMA)-approved EGFR TKIs in cell lines, xenograft models and humans, in order to obtain a practical guide for refining the clinical decision-making process.

Keywords: EGFR; NGS; NSCLC; Systematic review; TKIs; Uncommon mutations.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • ErbB Receptors / drug effects
  • ErbB Receptors / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Male
  • Mutation / genetics
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Treatment Outcome

Substances

  • Protein Kinase Inhibitors
  • ErbB Receptors