2025 Targeted Therapies of Lung Cancer (TTLC) - Posters-PP01.24 Clinical Characteristics and Outcomes of Patients with Germline EGFR Mutations: A Single Institution Experience

PP01.24 Clinical Characteristics and Outcomes of Patients with Germline EGFR Mutations: A Single Institution Experience

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This study examines the clinical characteristics and outcomes of patients with germline EGFR mutations treated at a single institution, Duke University. Germline EGFR mutations, particularly T790M, account for 1% of non-small cell lung cancer (NSCLC) cases and have been identified in a familial form in the southeast United States. The research is part of the INHERIT study, which aimed to document hereditary EGFR-mutant lung cancers.<br /><br />The retrospective analysis included patients in the Duke Molecular Registry of Tumors, highlighting that putative germline EGFR mutations were more prevalent in non-smoking females, with many having a family history of cancer, indicating heritability. Among cancer patients studied, 80% harbored T790M mutations, with other EGFR mutations like R776H and E709R also identified. Additionally, 85% of these patients had co-mutations, most frequently a secondary EGFR mutation or TP53, with an average of 2.95 co-mutations per patient.<br /><br />The median age at cancer diagnosis was 58 years, predominantly affecting females (60%) and non-smokers (70%). Most patients were treated with the targeted therapy osimertinib, with an average treatment duration of 30 months. Osimertinib treatment demonstrated comparable overall survival to other EGFR-mutated cases, averaging 39 months. Notably, some patients remain on treatment, and 12 were alive at the data analysis time.<br /><br />A significant portion (80%) had at least one first-degree relative with a malignancy, reinforcing the potential hereditary nature of these mutations. Data from the Duke CATHGEN project and the gnomAD database indicated the frequent occurrence of EGFR mutations like T790M, with high penetrance suggested as a portion of those studied already had lung cancer or nodules. This highlights the need for further exploration of germline EGFR mutations and their implications in cancer development and treatment strategies.

Asset Subtitle

Jenny O'Brien

Keywords

germline EGFR mutations

T790M mutation

non-small cell lung cancer

INHERIT study

Duke University

osimertinib treatment

hereditary lung cancer

non-smoking females

familial cancer

co-mutations