Abstract

Clinical implications of genomic variants identified in over 30,000 advanced-stage cancer patients by next-generation sequencing of circulating tumor DNA

AmirAli Talasaz, Co-Founder, President & COO, Guardant Health

Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) enables non-invasive profiling of solid tumor cancers. Over the past few years, research and clinical practice guidelines have highlighted a role for liquid biopsy in patient care. In addition, liquid biopsies are becoming essential for successful patient enrollment in clinical trials, where tissue access and high rate of failures have been limiting factors slowing enrollment. In this talk, we characterize somatic genomic profiles derived from over 35,000 plasma samples from advanced cancer patients as were determined by a ctDNA NGS test targeting up to 73 genes (Guardant360®). Accuracy of ctDNA-detected driver alterations (PPV) was assessed by comparing to available matched tissue tests for 646 patients (lung, colon, and other cancer types). A pooled response rate analysis was performed across 11 published/pre-press datasets analyzing response to Guardant360®-directed therapy. Use of liquid biopsies is increasing in clinical care, providing an option of obtaining genomic information non-invasively. This dataset, derived from liquid biopsy use in clinical practice, highlights the clinical impact of identifying alterations that are targetable by drugs with regulatory approval, including emergent resistance alterations, as well as novel targets.