2024 Hot Topic in Basic & Translational Science: Tolerance & Resistance to Targeted Therapy in NSCLC - Posters-PP01.20: Predictive Utility of Circulating Tumor DNA in First- Line Osimertinib Therapy for EGFR-Mutant Metastatic Lung Adenocarcinoma

PP01.20: Predictive Utility of Circulating Tumor DNA in First- Line Osimertinib Therapy for EGFR-Mutant Metastatic Lung Adenocarcinoma

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The study examined the role of circulating tumor DNA (ctDNA) levels, specifically the variant allele frequency (VAF) of EGFR mutations, in predicting the efficacy of first-line osimertinib therapy in patients with EGFR-mutant metastatic lung adenocarcinoma. Conducted as a single-center retrospective analysis using data from January 2018 to March 2024, 46 patients with confirmed metastatic lung adenocarcinoma (mLUAD) participated, all having undergone pre-treatment liquid biopsies and receiving only osimertinib as their initial therapy.<br /><br />Key findings indicated that a higher VAF was associated with significantly extended progression-free survival (PFS). Patients with higher VAF levels had a median PFS of 15.24 months compared to just 3.68 months for those with lower VAF levels, with a hazard ratio (HR) of 4.86 (p=0.01), suggesting that higher ctDNA levels might be indicative of better response to treatment. Additionally, exon 19 mutations showed a more favorable prognosis with longer PFS (8.64 months) compared to exon 21 mutations (2.30 months), highlighting the importance of specific EGFR mutation profiles in predicting treatment outcomes.<br /><br />The study concludes that ctDNA VAF, especially regarding specific exon mutations, could serve as a predictive biomarker to guide treatment decisions in metastatic lung adenocarcinoma. Notably, patients without detectable mutated EGFR in ctDNA, referred to as 'non-shedders,' demonstrated better outcomes compared to those with detectable mutations, although this finding was not statistically significant (p=0.11). These insights could potentially refine therapeutic strategies for patients based on individual genetic profiles, underscoring the utility of liquid biopsy in precision oncology.

Asset Subtitle

Rodrigo Paredes

Keywords

circulating tumor DNA

ctDNA

variant allele frequency

VAF

EGFR mutations

osimertinib therapy

metastatic lung adenocarcinoma

progression-free survival

liquid biopsy

precision oncology