Clinical characteristics and treatment of EGFR exon 19 L747 mutation in advanced NSCLC: a retrospective study

This study investigates the clinical characteristics, targeted therapy outcomes, co-mutations, and prognosis of lung cancer patients with EGFR exon 19 (ex19) L747 mutations in Northwest China, providing insights for treating these rare mutations. We retrospectively analyzed advanced NSCLC patients with EGFR ex19 L747 mutations, identified from January 2020 to August 2024 at Xijing Hospital, using next-generation sequencing for mutation detection. Comprehensive clinical data, including molecular profiles, treatment regimens, and efficacy, were evaluated, accompanied by three illustrative case studies. Among ten patients (70.0% female, median age 56.5 years, 80.0% nonsmokers), three had L747P and seven had L747_P753delinsS mutations. Common co-mutations included TP53 (50.0%), RB1 (10.0%), MED12 (10.0%), BRCA1 (10.0%), SMARCA4 (10.0%), and HER2 (10.0%). Treatment involved EGFR-TKIs combined therapy, achieving an objective response rate (ORR) of 20.0%, median progression-free survival (mPFS) of eight months (95% CI, 5-not reached), and median overall survival (mOS) of 32 months (95% CI, 21-not reached). In the L747_P753delinsS group (n = 7), third-generation EGFR-TKIs produced one CR, with an ORR of 14.3%, mPFS of 12 months (95% CI, 6-not reached), and mOS not reached (95% CI, 23.3-not reached). Two L747P patients with TP53 co-mutations receiving afatinib showed PFS of 1.5 and 15 months; those with L747_P753delinsS mutations and TP53 co-mutations on third-generation EGFR-TKIs had PFS of 12 and 16 months. EGFR ex19 L747 mutations, particularly L747P, are rare and exhibit heterogeneous responses to varying generations of EGFR-TKIs. L747P shows limited response to first- and third-generation TKIs but improved outcomes with afatinib. L747_P753delinsS mutations favor third-generation TKIs. Larger studies are needed for validation.