Successful Treatment of Afatinib Reversing Epidermal Growth Factor ReceptorExon19Deletion/G724S MutationResistance Guided byProtein-DrugDocking

Abstract

G724S is a rare mutation induced by different generations of TKIs. No clinical effective drugs towards G724S mutation have been reported till now. We analysed the interaction of three drugs(Afatinib, Gefitinib, Osimertinib) with 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 Afatinib remains effective to EGFR Ex19Del+G724S mutant patients while Osimertinib and Gefitinib 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(PFS) of more than 1 year. With the guidance of this case report, we provide the clinical evidence of using Afatinib for G724S-mutant patients and obtain long-term clinical survival. The Oncologist 2021;9999:• •