Multicenter Validation Study to Implement Plasma Epidermal Growth Factor Receptor T790M Testing in Clinical Laboratories

Abstract

PURPOSE Plasma detection of EGFR T790M mutations is an emerging alternative to tumor rebiopsy in acquired epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance. Validation of analytical sensitivity and clinical utility is required before routine diagnostic use in clinical laboratories. PATIENTS AND METHODS Sixty-three patients with advanced EGFR-mutant lung cancer at 7 Canadian centers, who were being screened for the ASTRIS trial (ClinicalTrials.gov identifier: NCT02474355 ), participated in this companion study. Plasma T790M mutation was detected using droplet digital polymerase chain reaction, Cobas (Roche Diagnostics, Indianapolis, IN), or next-generation sequencing in 4 laboratories. T790M concordance was assessed between plasma and tumor samples. RESULTS Assessment of T790M in tumor biopsy tissue was successful in 81% of patients; 49% had confirmed T790M results (tumor or plasma) for ASTRIS. Plasma testing in this companion study yielded T790M results in 97% of patients; 62% had T790M-positive results, 36% had negative results, and 2% had indeterminate results. Of 38 patients with negative or indeterminate biopsy results, 55% had positive plasma T790M results, increasing the proportion with T790M-positive results to 73%. Sensitivity of plasma T790M testing was 75%. Overall concordance between tissue and plasma was 64%, and concordance among laboratories was 90.3%. Response to osimertinib and duration of therapy were similar irrespective of testing method (overall response rate, 62.5% for tissue, 66.7% for plasma, and 70.6% for both). CONCLUSION This multicenter validation study demonstrates that plasma EGFR T790M testing can identify significantly more patients than biopsy alone who may benefit from targeted therapy.

Reflex ROS1 IHC Screening with FISH Confirmation for Advanced Non-Small Cell Lung Cancer—A Cost-Efficient Strategy in a Public Healthcare System

“…Although such platforms offer broad-based testing of known and unknown variants, non-NGS PCR-based ctDNA assays (either as a single gene or multiplexed), known to be highly sensitive for detecting a select few targetable alterations, may still offer a lower-cost alternative in resource-limited settings. However, liquid biopsy has been shown to help to avoid repeat tissue biopsy in patients with small samples, increase the identification of patients with actionable alterations, which may offset costs and offer short TAT [26,50]. Furthermore, it is expected that the costs of liquid biopsy technology will decrease over time, and the use of non-commercial assays or price negotiation may make this strategy more affordable in future.…”

Integrating circulating-free DNA (cfDNA) analysis into clinical practice: opportunities and challenges

“…Several studies have shown the clinical utility of T790M detection in ctDNA using various platforms leading to implementation of liquid biopsy in this clinical setting. For patients with a plasma T790M-negative result, reflex tissue biopsy and tissue genotyping is recommended [ 56 – 58 ]. Osimertinib, a third-generation EGFR inhibitor, has now moved to the first-line setting as treatment for patients with advanced EGFR mutant NSCLC [ 24 ].…”

Phase II open‐label multicenter study to assess the antitumor activity of afatinib in lung cancer patients with activating epidermal growth factor receptor mutation from circulating tumor DNA: Liquid‐Lung‐A

“…In a Canadian validation study of plasma EGFR T790M testing, plasma testing showed more T790M‐positive results (62%) than tumor biopsy alone (49%), with 75% sensitivity using highly sensitive methods such as ddPCR, next‐generation sequencing, and RT‐PCR 26 . Therefore, ctDNA EGFR analysis could be used in clinical practice as a routine diagnostic tool in a post‐EGFR‐TKI setting and for initial screening at diagnosis.…”