Lung adenocarcinoma harboring uncommon EGFR exon 19 deletion L747_T751del and in cis K754E mutation: a case report and literature review

E746_A750del, the most common and predominant EGFR exon 19 deletion in non-small cell lung cancer, shows excellent sensitivity to EGFR tyrosine kinase inhibitors. However, other uncommon EGFR exon 19 deletions show varying responses to EGFR-targeted inhibitors. L747_T751del is a rare EGFR exon 19 deletion, with uncertain clinical sensitivity to EGFR-targeted inhibitors. Additionally, K754E in exon 19 is another rare EGFR alteration with potentially damaging consequences and lack of established.drug response patterns. Limited research exists regarding the structure and implications of L747_T751del and in cis K754E mutation both in exon 19 of EGFR and sensitivity prediction of K754E mutation to EGFR-targeted inhibitors. Herein, we presented a case of a non-small cell lung cancer patient harboring an uncommon EGFR exon 19 deletion L747_T751del with in cis K754E mutation. A 41-year-old male with metastatic lung adenocarcinoma received gefitinib as the first-line treatment. Following disease progression after one year, leptomeningeal metastasis developed. Subsequent osimertinib treatment at 80 mg or 160 mg doses once daily proved ineffective for intracranial disease control. The patient's leptomeningeal metastasis symptoms progressively worsened during osimertinib treatment. Drug binding dynamics simulation indicated reduced binding activity of osimertinib to L747_T751del and K754E mutation sites as compared to other third- or second-generation EGFR-targeted inhibitors. This study provides the first comprehensive investigation of the L747_T751del and in cis K754E mutation and its interaction with EGFR-targeted inhibitors, offering valuable clinical guidance for treating uncommon EGFR exon 19 mutations.