Accelerating treatment decisions with liquid biopsy NGS in non-small cell lung cancer.

e20536 Background: Next Generation Sequencing (NGS) to identify actionable biomarkers has revolutionized non-small cell lung cancer (NSCLC) treatment, thus improving survival for patients with actionable mutations who receive targeted therapy. Plasma-based liquid biopsies offer a faster, less invasive alternative for analyzing circulating tumor DNA compared to tissue-based methods. When used alongside tissue biopsies, liquid biopsies streamline treatment decisions and patient outcomes. This study evaluated recently diagnosed metastatic or recurrent NSCLC patients sequenced with both biopsy types to assess biopsy impact on diagnostic efficiency and treatment initiation. Methods: This retrospective study reviewed adult patients with advanced NSCLC treated at Memorial Cancer Institute who underwent both tissue (physician’s choice) and liquid NGS testing, via Guardant360®, between July 1, 2015, and September 1, 2024. We examined patient demographics, clinical characteristics, and biopsy-specific details, including turnaround time (TAT) and time to treatment decision (TtT). Statistical analyses for TAT and TtT were performed using unpaired t-tests. Treatment decision was based on the available sample report, affected by insufficient quality or label alterations. Results: The study included 354 NSCLC patients, the majority of whom were white (79.4%), non-Hispanic (63.6%), female (54.5%), former smokers (63.8%), and diagnosed with adenocarcinoma (89.5%). Liquid biopsy NGS showed a significant reduction in TAT compared to tissue biopsy, with a median difference of 12 days (8 vs 20 days, respectively, p<0.0001). Liquid biopsy alone was used to guide treatment decisions in 80.5% of cases. Additionally, liquid biopsy was associated with significantly shorter TtT compared to tissue biopsy, with medians of 23 days vs 32 days for any treatment and 20 days vs 34 days for targeted therapy (p≤0.0046). In treatment-naive patients, liquid biopsy demonstrated a numerically faster TtT than tissue biopsy, with a median difference of 7 days (22 vs. 29 days) overall and 12 days (15 vs. 27 days) for those receiving targeted therapy (p≤0.0548). Notably, 13.0% of tissue biopsy samples were not reported due to insufficient sample quality (QNS), whereas all liquid biopsy samples successfully yielded reportable results. On-label alterations were detected in both biopsies with concordance >96% across genes. Conclusions: This study highlights the value of NGS liquid biopsy in improving comprehensive genomic profiling and expediting diagnosis and treatment decisions in patients with advanced NSCLC with 80% of treatment decisions based on liquid NGS results. Liquid biopsy demonstrated other significant advantages over tissue NGS, including faster TAT, shorter TtT, and higher sample success rates. These findings underscore the complementary role of liquid biopsy alongside tissue biopsy in streamlining diagnostic workflows and advancing precision medicine for advanced NSCLC.