2024 World Conference on Lung Cancer (WCLC) - Posters-P1.12A.11 Analysis of Uncommon EGFR Exon 19 Alterations Identified by Liquid Biopsy in Advanced Non-Small Cell Lung Cancer (NSCLC)

P1.12A.11 Analysis of Uncommon EGFR Exon 19 Alterations Identified by Liquid Biopsy in Advanced Non-Small Cell Lung Cancer (NSCLC)

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The study by Jason Porter, MD, and colleagues at the West Cancer Center & Research Institute, explores the prevalence and implications of uncommon EGFR exon 19 deletions (ex19del) in non-small cell lung cancer (NSCLC) using liquid biopsy data. EGFR ex19del mutations, comprising 40 different indels, present challenges in treatment, particularly with the use of EGFR tyrosine kinase inhibitors (TKIs) due to mixed response rates and limited studies on co-alterations and resistance mechanisms.<br /><br />The analysis included data from Guardant360 testing conducted between February 2015 and September 2023 on NSCLC patients with identified ex19del mutations. Within this study, mutations were classified as "common" or "uncommon" using public data sources, and the cohort was analyzed at different timepoints: initially without therapy (T0) and when not responding to therapy (Tother).<br /><br />Findings reveal that most patients had common EGFR ex19del mutations at both T0 and Tother timepoints. Significant differences in the prevalence of co-occurring alterations over time were observed, with mutations such as EGFR T790M, C797S, and G724S being more prevalent in the Tother cohort, suggesting an association with acquired resistance.<br /><br />The study used statistical analyses, including Fisher’s Exact Test, to compare alterations, which indicated significant differences in co-alterations both in EGFR and non-EGFR genes between patients with common and uncommon ex19del mutations.<br /><br />The research concludes that while genomic findings are similar across common and uncommon ex19del groups, additional research is crucial to understand the broader genomic and non-genomic factors that may assist in selecting appropriate EGFR TKIs for patients with uncommon ex19del findings. This work is described as one of the largest liquid biopsy analyses to date in this context, offering insights for enhancing clinical decision-making in NSCLC treatment.

Asset Subtitle

Jason Porter

Meta Tag

Speaker Jason Porter

Topic Metastatic NSCLC – Targeted Therapy

Keywords

EGFR exon 19 deletions

non-small cell lung cancer

NSCLC

liquid biopsy

EGFR tyrosine kinase inhibitors

TKIs

Guardant360

co-alterations

resistance mechanisms

genomic factors