2024 Asia Conference on Lung Cancer (ACLC) - Poster & ePosters-PP02.66

PP02.66 - Wenfeng Fang

Pdf Summary

In a study of lung cancer patients with EGFR L747X mutations, researchers aimed to understand the molecular characteristics and therapeutic responses due to the low prevalence and frequent misidentification of these mutations via routine PCR. Using next-generation sequencing (NGS) of 41,369 lung cancer patients, EGFR mutations were found in 17,084 patients, of which 68 were identified as EGFR L747X, representing 0.4% of EGFR-mutated NSCLC cases. Among these, EGFR L747P mutations often existed as single mutations, unlike EGFR L747S and L747V.<br /><br />The study further utilized Ba/F3 cells expressing EGFR L747 mutants to evaluate the efficacy of various EGFR tyrosine kinase inhibitors (TKIs) and employed structural modeling to predict binding affinities. Results indicated that afatinib showcased superior sensitivity and a higher binding affinity for these mutations compared to other EGFR TKIs like osimertinib and erlotinib.<br /><br />Clinically, retrospective analyses revealed that patients with EGFR L747X mutations treated with afatinib or chemotherapies experienced longer progression-free survival (PFS) compared to those receiving first-generation (1G) or third-generation (3G) TKIs. These findings suggest that afatinib may offer a more effective treatment option for NSCLC patients with these specific mutations.<br /><br />The research provides key insights into the molecular structure and treatment response of rare EGFR L747X mutations, highlighting the potential of afatinib as a preferred therapeutic avenue, thus emphasizing the importance of precise molecular characterization in tailoring cancer treatments. This work represents the first comprehensive NGS-based analysis of EGFR L747X mutations, offering significant data to guide clinical decisions and improve outcomes for affected NSCLC patients.

Keywords

EGFR L747X mutations

lung cancer

next-generation sequencing

EGFR tyrosine kinase inhibitors

afatinib

progression-free survival

molecular characterization

NSCLC

therapeutic responses

Ba/F3 cells