Lessons learned from routine, targeted assessment of liquid biopsies for EGFR T790M resistance mutation in patients with EGFR mutant lung cancers

Abstract

Background: Plasma cfDNA evaluation at acquired resistance to targeted therapies in lung cancer is routine, however, reports of extended clinical application and pitfalls in laboratory practice are still limited. In this study we describe our experience with cfDNA testing using EGFR T790M as a prototype. Methods: Patients with metastatic EGFR-mutant NSCLC patients who underwent plasma EGFR T790M testing at acquired resistance to EGFR tyrosine kinase inhibitors (EGFR-TKI) from January 2016 through August 2017 were identified. Molecular laboratory records were reviewed to assess performance of testing by digital PCR, concordance between plasma and tissue testing, turnaround time (TAT), plasma T790M variant allele frequency (VAF), and its correlations with metastatic sites and clinical outcomes. Results: 177 patients underwent T790M cfDNA testing during this period. Plasma T790M was positive in 32% of patients. The median TAT was shorter for plasma T790M compared to tissue PCR (9 vs. 15 days, p