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

• Published in: The oncologist (Dayton, Ohio) Vol. 26; no. 11; pp. e1903 - e1908
• Main Authors: Yu, Nian, Xu, Yinghui, Wang, Xu, Sun, Chao, Qiu, Shi, Guo, Ye, Bai, Miao, Huang, Yanxin, Ma, Kewei
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.11.2021; Oxford University Press
• Subjects: Adenocarcinoma - drug therapy; Afatinib; Afatinib - therapeutic use; Diagnosis; Drug therapy; Epidermal growth factor receptor G724S mutation; ErbB Receptors - genetics; Genetic aspects; Humans; Lung cancer; Male; Mutation; Non‐small cell lung cancer; Precision Medicine Clinic: Molecular Tumor Board; Protein structure remodeling; China; Afatinib; Epidermal growth factor receptor G724S mutation; Protein structure remodeling; Non-small cell lung cancer
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1002/onco.13932

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. This brief communication presents the case of a patient with acquired Ex19Del/G724S mutation who was treated with afatinib and obtained long‐term clinical benefit.