Therapy for Advanced NSCLC With EGFR 19delins Mutation

In a retrospective analysis of 3,054 advanced NSCLC patients, 41 with EGFR exon 19 deletion-insertions (19delins) received first-generation EGFR TKIs, achieving median PFS of 10.4 months; those with L747\_T751delinsP had notably longer PFS of 18.7 months. Another study of 2,467 treatment-naïve patients found 93 with 19delins treated with first-generation TKIs had median PFS of 19 months, exceeding the 13 months for common 19del mutations. For third-generation TKIs, a study of 215 19delins patients (57 first-line) showed median PFS of 12.9 months, inferior to 23.2 months for common 19del. Our center's retrospective study of 4,666 NSCLC patients in Fujian (2017-2020) included 69 with 19delins: median PFS was 16.7 months with first-generation TKIs versus 7.2 months with third-generation. Evidence suggests specific EGFR deletion locations may affect TKI efficacy; first-generation TKIs may be superior in some 19delins subtypes, while third-generation appear limited. Large prospective data are lacking. This project aims to compare first- versus third-generation EGFR TKIs in 19delins patients via a randomized controlled trial, stratify sensitivity by subtype, and improve survival.