2024 World Conference on Lung Cancer (WCLC) - Posters-P1.03D.04 Circulating APOBEC Signature as a Non-Invasive Biomarker Delineating Potential Responder to Neoadjuvant Immunotherapy for IIIA-N2 NSCLC

P1.03D.04 Circulating APOBEC Signature as a Non-Invasive Biomarker Delineating Potential Responder to Neoadjuvant Immunotherapy for IIIA-N2 NSCLC

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This study investigates the potential of using the circulating APOBEC mutation signature as a non-invasive biomarker to predict the efficacy of neoadjuvant immunotherapy (NAI) in patients with resectable non-small cell lung cancer (NSCLC). Utilizing data from a phase II trial (NCT04422392), this research examines the correlation between pre-treatment circulating tumor DNA (ctDNA) genomic signatures and therapeutic outcomes of NAI.<br /><br />APOBEC, an enzyme involved in RNA editing, has been linked to immunotherapy effectiveness in NSCLC, though its clinical and biological significance as a predictor remains uncertain. This study aims to address these questions by leveraging advanced genomic profiling techniques on tissue samples, plasma, and peripheral blood mononuclear cells collected from patients undergoing Sintilimab with chemotherapy as NAI.<br /><br />Key findings of the study include significant concordance between tissue and circulating APOBEC signatures, suggesting that ctDNA could reflect the tumor's mutational landscape accurately. Patients exhibiting APOBEC-positive signatures demonstrated enhanced neoadjuvant responses, as evidenced by the mutational landscape analysis, highlighting its potential efficacy as a predictive biomarker for immunotherapy response.<br /><br />Further validation through Kaplan-Meier curves and multivariate analyses supported the association between APOBEC status and improved progression-free survival rates in patients treated with immunotherapy regimens such as Atezolizumab and Docetaxel. These insights underscore the potential of integrating circulating APOBEC status into clinical decision-making, potentially paving the way for personalized treatment approaches that could significantly improve patient outcomes in NSCLC therapy. Overall, the study proposes APOBEC as a promising novel biomarker in the non-invasive prediction of immunotherapy success.

Asset Subtitle

Changbin Zhu

Meta Tag

Speaker Changbin Zhu

Topic Tumor Biology – Translational Biology

Keywords

APOBEC mutation signature

non-invasive biomarker

neoadjuvant immunotherapy

non-small cell lung cancer

circulating tumor DNA

genomic profiling

Sintilimab chemotherapy

predictive biomarker

progression-free survival

personalized treatment