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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.