Successful treatment of an osimertinib-resistant lung adenocarcinoma with an exon 18 EGFR mutation (G719S) with afatinib plus bevacizumab

Invest New Drugs. 2021 Feb;39(1):232-236. doi: 10.1007/s10637-020-00966-7. Epub 2020 Jun 18.


Exon 18 mutations account for only 3.6% of EGFR mutations, and tumors with exon 18 mutations are often unresponsive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We present a novel case of a lung adenocarcinoma with an exon 18 mutation resulting in a glycine to serine substitution at position 719 of the EGFR protein. The patient received osimertinib, a third generation EGFR-TKI, as the first-line treatment, but the disease progressed during treatment. Analysis of circulating free DNAs via next generation sequencing revealed TP53 mutations and EGFR and MET amplifications, as well as the exon 18 mutation. On the basis of these results, we administered afatinib, a second-generation TKI, and bevacizumab, a vascular endothelial growth factor inhibitor, as the second-line treatment. The patient's symptoms improved, and this treatment was continued for 12 months. This report suggests that afatinib plus bevacizumab can effectively treat osimertinib-refractory lung tumors with an exon 18 mutation.

Keywords: Afatinib plus bevacizumab; Circulating free DNA; Exon 18 EGFR mutation; NGS; Osimertinib resistance; Uncommon mutation.

Publication types

  • Case Reports

MeSH terms

  • Acrylamides / pharmacology
  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / genetics
  • Adult
  • Afatinib / therapeutic use*
  • Aniline Compounds / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab / therapeutic use*
  • Drug Resistance, Neoplasm
  • ErbB Receptors / genetics
  • Exons
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Male
  • Mutation


  • Acrylamides
  • Aniline Compounds
  • Bevacizumab
  • osimertinib
  • Afatinib
  • EGFR protein, human
  • ErbB Receptors