2024 World Conference on Lung Cancer (WCLC) - Posters-P3.06D.04 Role of ctDNA Variant Allele Frequency in Predicting Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

P3.06D.04 Role of ctDNA Variant Allele Frequency in Predicting Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer

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This study examines the potential of circulating tumor DNA (ctDNA) Variant Allele Frequency (VAF) as a predictive biomarker for response to immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC). Current standard predictive markers for ICI therapy include PD-L1 expression levels, but emerging data suggest that VAF might also offer predictive value.<br /><br />A retrospective analysis was conducted from January 2018 to March 2024, involving 463 NSCLC patients who underwent liquid biopsies at initial diagnosis, with ctDNA analyzed using Guardant360. The study focused on 104 patients who received ICI, comparing high VAF (≥1%) to low VAF (<1%) in terms of overall survival (OS) and PD-L1 expression levels.<br /><br />Key findings include:<br />- Patients with high VAF experienced significantly shorter OS (median 6.16 months) compared to those with low VAF (median 13.83 months), with a p-value of 0.03 indicating statistical significance.<br />- High VAF was associated with a higher adjusted mortality risk (Hazard Ratio: 2.55).<br />- There was a significant negative correlation between total VAF levels and PD-L1 % expression (p-value 0.02).<br /><br />The study suggests that elevated VAF levels in ctDNA correlate with lower PD-L1 expression and poorer survival outcomes in NSCLC patients treated with ICIs. Consequently, total VAF could serve as a useful predictive biomarker for assessing ICI therapy outcomes, potentially aiding in more personalized treatment approaches. This could enhance decision-making in clinical settings, guiding therapy choices based on a more comprehensive understanding of tumor behavior.<br /><br />Correspondence for further information can be directed to Dr. Christian Rolfo at The Ohio State University Comprehensive Cancer Center.

Asset Subtitle

Rodrigo Paredes de la Fuente

Meta Tag

Speaker Rodrigo Paredes de la Fuente

Topic Pathology & Biomarkers

Keywords

circulating tumor DNA

Variant Allele Frequency

immune checkpoint inhibitors

non-small cell lung cancer

predictive biomarker

PD-L1 expression

overall survival

Guardant360

personalized treatment

clinical decision-making