The Clinical Impact of Comprehensive Genomic Testing of Circulating Cell-Free DNA in Advanced Lung Cancer

Abstract

Introduction: Next-generation sequencing (NGS) of cell-free circulating tumor DNA (cfDNA) enables noninvasive genomic analysis of NSCLC patients. Although plasma-detected genomic alterations (GAs) have been shown to predict targeted therapy response, evidence of durability of response is lacking or limited to small cohorts as is the impact of cfDNA NGS results on clinical decisions.

Methods: This retrospective study of stage IIIB/IV NSCLC patients between the years 2014 and 2017 in Israel used cfDNA NGS (Guardant360; Guardant Health, Inc., Redwood City, California) to identify targetable GAs.

Results: We consecutively tested 116 NSCLC patients, 41.4% before first-line therapy (group A), 34.5% upon progression on chemotherapy or immunotherapy (group B1), and 24.1% upon progression on EGFR tyrosine kinase inhibitors (group B2). Targetable GAs were found in 31% of group A (15 of 48 patients), 32.5% in group B1 (13 of 40 patients) and 71% in group B2 (20 of 28 patients). Treatment decision was changed to targeted therapy in 23% (11 of 48 patients), 25% (10 of 40 patients) and 32% (9 of 28 patients), respectively (total cohort 26%; 30/116). Objective response rate (Response Evaluation Criteria in Solid Tumors) was 43% (12 of 28 patients) including one complete response, partial response in 39% (11 of 28 patients), stable disease in 32% (9 of 28 patients), and progressive disease in 25% (7 of 28 patients). Disease control rate was 75% for 5 months median treatment duration.

Conclusions: Comprehensive cfDNA testing impacted clinical decisions in one-quarter to one-third of initial and subsequent lines of treatment in advanced NSCLC patients. This retrospective study extends previous reports by showing that responses based on cfDNA are durable and change treatment decisions at initial presentation and at progression.

Keywords: Cell-free DNA; Liquid biopsy; Lung cancer; Next-generation sequencing; Personalized medicine; Targeted therapy.