Plasma ctDNA Analysis for Detection of the EGFR T790M Mutation in Patients with Advanced Non–Small Cell Lung Cancer
Journal
Journal of Thoracic Oncology
Journal Volume
12
Journal Issue
7
Pages
1061-1070
Date Issued
2017
Author(s)
Jenkins S
Ramalingam S.S
Yu K
Patel S
Weston S
Hodge R
Cantarini M
Jänne P.A
Mitsudomi T
Goss G.D.
Abstract
Introduction Tumor biopsies for detecting EGFR mutations in advanced NSCLC are invasive, costly, and not always feasible for patients with late-stage disease. The clinical utility of the cobas EGFR Mutation Test v2 (Roche Molecular Systems, Inc., Pleasanton, CA) with plasma samples from patients with NSCLC at disease progression after previous EGFR tyrosine kinase inhibitor therapy was investigated to determine eligibility for osimertinib treatment. Methods Matched tumor tissue and plasma samples from patients screened for the AURA extension and AURA2 phase II studies were tested for EGFR mutations by using tissue- and plasma-based cobas EGFR mutation tests. Plasma test performance was assessed by using the cobas tissue test and a next-generation sequencing method (MiSeq [Illumina Inc., San Diego, CA]) as references. The objective response rate, measured by blinded independent central review, was assessed in patients receiving osimertinib with a plasma T790M mutation–positive status. Results During screening, 551 patients provided matched tumor tissue and plasma samples. Pooled analysis of the positive and negative percent agreements between the cobas plasma and tissue tests for detection of T790M mutation were 61% and 79%, respectively. Comparing cobas plasma test with next-generation sequencing demonstrated positive and negative percent agreements of 90% or higher. The objective response rate was 64% (95% confidence interval: 57–70) in T790M mutation–positive patients by both cobas tissue and plasma tests (evaluable for response). Conclusions The cobas plasma test detected the T790M mutation in 61% of tumor tissue T790M mutation–positive patients. To mitigate the risk of false-negative plasma results, patients with a negative plasma result should undergo a tissue test where feasible. ? 2017 International Association for the Study of Lung Cancer
Subjects
circulating tumor DNA; MiSeq next-generation sequencing; osimertinib; Roche cobas EGFR Mutation Test; tumor tissue biopsy
SDGs
Other Subjects
chloroplast DNA; epidermal growth factor receptor; osimertinib; DNA; epidermal growth factor receptor; advanced cancer; Article; clinical decision making; cobas tissue test; controlled study; DNA determination; EGFR gene; false negative result; feasibility study; gene mutation; genetic screening; human; human tissue; intermethod comparison; major clinical study; mutational analysis; next generation sequencing; non small cell lung cancer; priority journal; risk assessment; tissue characterization; blood; female; genetics; lung tumor; male; mutation; non small cell lung cancer; pathology; Carcinoma, Non-Small-Cell Lung; DNA, Neoplasm; Female; Humans; Lung Neoplasms; Male; Mutation; Receptor, Epidermal Growth Factor
Publisher
Elsevier Inc
Type
journal article