Successful Treatment of Afatinib Reversing Epidermal Growth Factor Receptor Exon19Deletion/G724S Mutation Resistance Guided by Protein-Drug Docking

Oncologist. 2021 Nov;26(11):e1903-e1908. doi: 10.1002/onco.13932. Epub 2021 Sep 12.

Abstract

G724S is a rare mutation induced by different generations of tyrosine kinase inhibitors (TKIs). No clinical effective drugs toward G724S mutation have been reported till now. We analyzed the interaction of three drugs (afatinib, gefitinib, osimertinib) with epidermal growth factor receptor (EGFR) from three aspects: the spatial structure of the binding region, the scoring function value, and the interaction force between drug molecules and active center of EGFR. Our results indicate that afatinib remains effective to patients with EGFR Exon19Deletion(Ex19Del) and G724S mutations whereas osimertinib and gefitinib are not, which is consistent with other reports. Afatinib is reported to be effective against G724S mutation, but no long-term clinical survival has been reported till now. A patient with stage IV adenocarcinoma was found to have Ex19Del/G724S mutation. Treated with afatinib, he received a progression-free survival of more than 1 year. With the guidance of this case report, we provide the clinical evidence of using afatinib for patients with G724S mutations and obtaining long-term clinical survival. KEY POINTS: Guided by protein-drug docking, afatinib is more effective to EGFR G724S mutation compared with osimertinib and gefitinib. A patient with Ex19Del/G724S mutation obtained long-term survival with afatinib treatment.

Keywords: Afatinib; Epidermal growth factor receptor G724S mutation; Non-small cell lung cancer; Protein structure remodeling.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Afatinib* / therapeutic use
  • ErbB Receptors* / genetics
  • Humans
  • Male
  • Mutation

Substances

  • Afatinib
  • ErbB Receptors