2024 World Conference on Lung Cancer (WCLC) - Posters-P1.12A.10 Effect of De Novo Co-Mutations on Clinical Outcomes in Patients Receiving First-Line Osimertinib for EGFR-Mutated NSCLC

P1.12A.10 Effect of De Novo Co-Mutations on Clinical Outcomes in Patients Receiving First-Line Osimertinib for EGFR-Mutated NSCLC

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This study evaluates the impact of de novo genetic co-alterations on clinical outcomes of patients with EGFR-mutated non-small cell lung cancer (NSCLC) treated first-line with osimertinib. Conducted across four U.S. academic centers, it includes a retrospective analysis of 219 adult patients with metastatic NSCLC who underwent Next Generation Sequencing (NGS) to identify genetic mutations at diagnosis.<br /><br />Osimertinib is a standard first-line therapy for EGFR-mutated NSCLC, but its effectiveness can vary due to genetic variations. The study aimed to determine the frequency of genetic co-alterations and compare time to treatment failure (TTF) and overall survival (OS) between patients with different genetic profiles.<br /><br />The findings revealed that genetic alterations in the TP53 pathway are prevalent; however, the presence of co-alterations in any individual pathway did not significantly predict TTF or OS on osimertinib. Notably, a co-alteration of TP53 and PIK3CA was associated with poorer outcomes compared to cases without such mutations. Median TTF and OS were significantly shorter in patients with concurrent TP53 and PIK3CA mutations, suggesting this combination as a high-risk molecular subset.<br /><br />Further analysis indicated that primary EGFR mutation types and certain clinical features, such as CNS or bone metastases, are stronger predictors of treatment outcomes than co-alteration profiles. Specifically, the exon 19 deletion conferred a better prognosis compared to the exon 21 L858R mutation.<br /><br />The study concludes that while identifying high-risk genetic profiles could help tailor more effective initial treatment strategies, primary EGFR mutations and clinical characteristics remain more crucial in predicting patient outcomes. These insights could guide therapeutic decision-making to improve NSCLC patient care.

Asset Subtitle

Fangdi Sun

Meta Tag

Speaker Fangdi Sun

Topic Metastatic NSCLC – Targeted Therapy

Keywords

de novo genetic co-alterations

EGFR-mutated NSCLC

osimertinib

Next Generation Sequencing

TP53 pathway

PIK3CA mutations

treatment outcomes

exon 19 deletion

exon 21 L858R mutation

NSCLC patient care