Real-world utility of ctDNA NGS to identify matched targeted therapy

Liquid biopsy for plasma circulating tumour DNA (ctDNA) next generation sequencing (NGS) is a rapidly evolving science. Plasma ctDNA assays are now commercially available, and are increasingly adopted in the community with a paucity of evidence-based guidance on timing and value of this test. Sabari et al. sought to determine the feasibility and utility of plasma ctDNA NGS to identify matched targeted therapy in a real-world clinical setting. At two sites, a total of 27 patients with metastatic adenocarcinoma of the lung and unknown driver mutation or unknown resistance mechanism were enrolled.

Plasma ctDNA NGS identified a variety of oncogenic drivers with a short median turnaround time of 6 days (vs. 21 days for tissue NGS; p < 0.0001) and matched them to targeted therapy in 14 % of cases. Plasma ctDNA was more frequently detected at diagnosis of metastatic disease or at progression. In patients on therapy, ctDNA detection rate was 46 %, and in those off therapy, 73 % (odds ratio, 0.31; p = 0.02). The plasma NGS concordance rate with tissue NGS regarding driver mutations was 96 %; for tissue NGS concordance with plasma NGS, this was 60 %. The authors concluded that a positive finding in plasma is highly specific and can immediately guide treatment, whereas a negative finding might still require tissue biopsy.

Sabari JK et al., Liquid biopsy in the clinic: a prospective study of plasma ctDNA NGS in patients with advanced NSCLCs to matched targeted therapy. ASCO 2017, abstract 11536