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Updated: Jun 16, 2026
Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
Patterns of central nervous system disease and molecular landscape in epidermal growth factor receptor exon 20
Amanda Reyes1, Isa Mambetsariev1, Jeremy Fricke1
1Department of Medical Oncology and Therapeutics Research, City of Hope National Medical Center, Duarte, CA, USA.
Background:
Epidermal growth factor receptor exon 20 insertion mutations (EGFR ins20) constitute a distinct entity among EGFR mutations. Therefore, we aimed to characterize patterns of central nervous system (CNS) metastasis and molecular co-mutations in relation to survival in this population.
Methods:
Retrospective analysis of 80 patients with non-small cell lung cancer and EGFR ins20 mutations seen from 2014-2024 at a large institution and network sites to characterize patterns of metastasis and progression. Clinical outcomes were analyzed with overall survival (OS). Magnetic resonance imaging was used to assess central nervous system disease location and progression.
Results:
About 36.25% of the patients had progression in central nervous system with 7.5 % of patients having leptomeningeal disease. Patients with CNS progression had a similar median OS of 45.3 months (31.6-78.5 months) compared to patients without progression of 47.8 months [36.8, not estimated (NE)] with a hazard ratio of 1.21 [95% confidence interval (CI): 0.66-2.23, P=0.54]. Co-TP53 mutation was associated with lower median OS of 31.6 months (20.4-NE) compared to 47.8 months (42.8-72.3) in TP53 wild type; hazard ratio 1.79 (95% CI: 0.89-3.60, P=0.11).
Conclusions:
While progression in the central nervous system did not impact clinical outcomes in this patient population, the high rate of disease in the central nervous system does warrant consideration and tailoring treatment with central nervous system penetration. This subgroup continues to behave as a distinct population and as such requires unique treatment and treatment strategies.
