Clinical Impact of EGFR Mutation Subtypes on Treatment Outcomes in Advanced Non-Small Cell Lung Cancer: An Austrian Real-World Study

Background: Non-small cell lung cancer (NSCLC), particularly in advanced stages, has poor prognosis. The main objective of the study is to evaluate real-world treatment outcomes in advanced NSCLC patients harboring an EGFR mutation and being treated with TKIs. Methods: The EGFR mutation status was ascertained by next-generation sequencing. The observational cohort study used prospectively maintained registry data. Patient data were collected at two high-volume institutions in Austria between November 2020 and February 2025. The prevalence EGFR mutations was 11% (145 out of 1,267 patients). Results: Among 53 patients (stage IIIB or higher) with an EGFR mutation, median overall survival (OS) and median progression-free survival (PFS) were 17.7 months (95% CI: 10.4-24.9) and 14.2 months (95% CI: 7.4-20.9), respectively. A total of 36 patients harbored common EGFR mutations (exon 19 deletion or L858R point mutation) and exhibited a significantly better OS than those with an uncommon EGFR genotype (p < 0.005). Patients with exon 19 deletion (n = 25) showed the longest mOS, followed by those with L858R mutation (32.5 vs. 17 months). In multivariable analysis, EGFR common mutation subtype (HR = 3.71 95%CI: 1.23 – 11.2) was associated with better OS. Patients with common EGFR genotypes, especially exon 19 deletion obtained longer OS and PFS compared with those with uncommon mutations in exon 18-21. Conclusion: The results underscore the prognostic role of distinct EGFR genotypes and the urgency to determine the mutation status in non-small cell lung cancer patients to ensure the best treatment decision. The study also highlights the challenges regarding to EGFR uncommon mu-tations and the resulting need for further research to investigate alternative treatment options.