Molecular epidemiology and outcomes of EGFR exon 20 insertion in Korean patients with non-small cell lung cancer

Background: The treatment landscape for metastatic or advanced non-small cell lung cancer (aNSCLC) evolved with the development of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs). However, EGFR exon 20 insertion (E20ins) mutations remain challenging to target. This study delineates molecular epidemiology, clinical characteristics, treatments, and survival outcomes of patients with E20ins compared to other EGFR mutations. Methods: Electronic medical records (EMRs) from three major hospitals in South Korea were analyzed retrospectively. Patients diagnosed with aNSCLC and confirmed EGFR mutations between 2014 and 2019 were included. Demographics, clinical characteristics, and treatment outcomes were analyzed to compare the impact of different EGFR mutations on patient outcomes. Results: Among 2,209 patients with aNSCLC, 1,978 (89.5%) exhibited common EGFR mutations [exon 19 deletion (E19del) and a single point mutation from leucine to arginine at exon 21 (E21L858R)], and 53 (2.4%) had E20ins. E20ins patients demonstrated notably poorer survival outcomes, with median overall survival (OS) of 13.9 months [95% confidence interval (CI): 10.1–not reached] compared to 31.0 months (95% CI: 29.0–35.8) for those with common mutations. Among 810 aNSCLC patients tested by both next-generation sequencing (NGS) and polymerase chain reaction (PCR), 21 were positive for E20ins by NGS, and 13 were positive by PCR. Of the 21 E20ins positives detected by NGS, 10 (47.6%) were not detected by PCR, while 2 patients (0.3%) were only positive for E20ins by PCR. Conclusions: E20ins represents a small but significant subset of EGFR mutations in aNSCLC, with worse survival outcomes. The study also highlighted superior sensitivity of NGS over PCR in detecting E20ins. This underscores necessity for improved detection strategies and effective treatments tailored to this mutation subgroup.