Critical assessment in routine clinical practice of liquid biopsy for EGFR status testing in Non-Small Cell Lung Cancer – A single laboratory experience (LPCE, Nice, France)

Abstract Objectives The introduction of liquid biopsyusing PCR-based assays into routine practice has had a strong impact on the treatment of EGFR-mutated lung adenocarcinoma and is now commonly used for routine testing of EGFR mutations in certain clinical settings. To assess whether the claimed benefits of PCR-based assays hold true in daily practice at a multicenter clinical institution, we assessed how treatment decisions are affected by PCR-based assays for the analysis of EGFR mutations from plasma samples in a centralized laboratory (LPCE, Nice, France). Materials and Methods 345 samples were analyzed using the FDA-approved Cobas® EGFR Mutation Testv2 and 103 using the Therascreen® EGFR Plasma RGQ PCR Kit over three years (395 samples from 324 patients). Eleven plasma samples were validated independently using Cobas® at three institutions, and 130 samples were analyzed using Stilla® digital PCR. Clinical data were collected for 175/324 (54%) patients. Results Cobas® was superior to the Therascreen® assay and demonstrated 100% reproducibility. Digital PCR showed only 48%, 83% and 58% concordance with Cobas® for exon 19 deletions, L858R and T790Mmutations, respectively. Liquid biopsieshelped to inform and change treatment when resistance occurred and enabled the detection of EGFR mutations in patients when a tissue biopsy was unavailable. Conclusions PCR-based assays are a fast and convenient test, allowing the detection of primary and secondary EGFR mutations from plasma. Cobas® proved to be a reliable test, whereas digital PCR produced too many inconclusive results to be currently recommended as a principal testing device.