The Clinical Pathological Spectrum and Prognosis of NSCLC with EGFR Exon20 Insertions

Background. EGFR Exon20 insertion mutations represent a rare and highly heterogeneous mutation subtype in NSCLC, characterized by intrinsic insensitivity to conventional EGFR-TKI therapy and association with adverse prognosis. This study aims to comprehensively analyze the clinical characteristics, mutation site distribution patterns, and their prognostic implications in Chinese NSCLC patients harboring EGFR Exon20 insertion mutations. Methods. This retrospective cohort study consecutively enrolled patients with pathologically confirmed NSCLC and molecularlyconfirmed EGFR Exon20 insertion mutations diagnosed at Beijing Chest Hospital between January 2011 and August 2024. Clinicopathological data were systematically collected, and prognostic factors influencing progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier survival analysis and Cox proportional hazards regression modeling. Results. A total of 218 NSCLC patients with EGFR Exon20 insertion mutations were enrolled, with a median age of 59 years; the cohort was predominantly comprised of female patients (59.2%) and non-smokers (70.2%), with adenocarcinoma representing 98.2% of cases. Near-loop mutations accounted for 70.9% (112/164) of cases, whereas far-loop mutations represented 29.1% (46/164). Among all 218 patients, 149 (68.3%) underwent PD-L1 testing, with 63.8% demonstrating negative expression. The majority of patients (67.9%, 148/218) presented with early-stage (I-II) disease. Among the 111 surgically treated early-stage patients with complete follow-up, only one recurrence and no deaths were observed, indicating favorable outcomes. Advanced-stage (stage III–IV) patients were significantly more prevalent in the far-loop mutation subgroup (p = 0.0037). Co-mutations were detected in 56.3% (86/164) of patients, with TP53 being the most frequently co-mutated gene (37.7%). For the 53 advanced-stage patientswith complete treatment and follow-up data, the median PFS and OS were 10.35 months and 20.93 months, respectively. Univariate analysis of PFS identified clinical N stage and baseline brain metastasis as significant prognostic factors (p = 0.011 and p = 0.018, respectively). Conclusion. In NSCLC patients with EGFR Exon20 insertion mutations, baseline brain metastasis emerges as an independent risk factor significantly influencing PFS. Patients with near-loop and far-loop mutations exhibit comparable clinical characteristics and survival outcomes overall.