Lung Adenocarcinoma Harboring Triple Rare EGFR Exon 18 Mutations Rapidly Developed Resistance to Multiple Therapies

Chemotherapy. 2022;67(4):248-252. doi: 10.1159/000525623. Epub 2022 Jun 28.


There is no standard therapy for nonsmall-cell lung cancer harboring rare coexistent EGFR mutations. Here, we report a female patient who was diagnosed as lung adenocarcinoma with three mutations of G724S, E709K, and V689I in exon 18. The patient responded to, but also showed rapid development of resistance to multiple therapies, including a second-generation EGFR-TKI of afatinib, a platinum-based doublet chemotherapy, and a multiple target TKI of anlotinib. As such, she ended up with a short overall survival time. Further research is required to understand the resistance mechanism(s) of these complex gene mutations.

Keywords: Complex mutations; EGFR-TKIs; Nonsmall-cell lung cancer; Rapid resistance; Rare EGFR mutation.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma of Lung* / drug therapy
  • Adenocarcinoma of Lung* / genetics
  • ErbB Receptors / genetics
  • Exons
  • Female
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use


  • ErbB Receptors
  • Protein Kinase Inhibitors
  • EGFR protein, human