P89.08 Real-World Impact of Plasma Cell-Free DNA Next-Generation Sequencing to Detect Actionable Genomic Alterations in Advanced NSCLC

Abstract

Next-generation sequencing (NGS) of plasma cell-free circulating tumor DNA (cfDNA) enables noninvasive comprehensive genomic analysis. The ability of cfDNA NGS to detect actionable genomic biomarkers in advanced non-small cell lung cancer (NSCLC) has been reported, but there are limited data on real-world usage. Here we prospectively collected the real-world cfDNA NGS data of treatment naive patients and also patients after progression to chemotherapy and/or immunotherapy and tyrosine kinase inhibitors (TKI) with negative tissue results for conventional tesing which we easily encounter in clinical practice. We analyzed data from advanced NSCLC patients who underwent cfDNA NGS (Guardant360; Guardant Health, Inc.) between December 2018 and January 2020 in the clinical practice. Information regarding patient and disease characteristics, treatment decisions, and clinical outcomes were collected. Genomic alterations were considered actionable if they were included in the Onco-KB precision oncology knowledge database and classified in one of four levels of actionability based on the preclinical or clinical evidence. Among 405 patients, 35.1% were female; 81.2% had adenocarcinoma (LuAd). At the time of plasma collection for NGS, 143 patients (35.3 %) were treatment-naïve, 177 patients (43.7%) had progressed after chemotherapy and/or immunotherapy, and 61 patients (15.1%) had progressed after tyrosine kinase inhibitor (TKI). Tumor DNA was detectable in 356 plasma samples (87.9 %). Regarding LuAd potentially actionable level 1-4 genomic alterations were detected in 177 cases (53.6%), of which 82 patients (24.9%) had level 1-2 alterations. Twelve patients who had started treatment based on tissue data had their treatment changed due to cfDNA NGS results. At the time of data cut-off, one of these patients had a partial response, 6 had stable disease, and 5 were not yet evaluated. Real-world cfDNA testing identified actionable genomic alterations in NSCLC not only when tissues were unavailable but also when conventional testing failed to detect actionable biomarkers. This study demonstrated that gene profiling of NSCLC using comprehensive cfDNA NGS can be a more efficient and faster strategy for deciding the therapeutic options at initial diagnosis and after progression.