EGFR Mutation Analysis for Prospective Patient Selection in Two Phase II Registration Studies of Osimertinib
Journal
Journal of Thoracic Oncology
Journal Volume
12
Journal Issue
8
Pages
1247-1256
Date Issued
2017
Author(s)
Jenkins S
Jänne P.A
Thress K.S
Yu K
Hodge R
Weston S
Dearden S
Patel S
Cantarini M
Shepherd F.A.
Abstract
Introduction Osimertinib is an oral, central nervous system–active, EGFR tyrosine kinase inhibitor (TKI) for the treatment of EGFR T790M–positive advanced NSCLC. Here we have evaluated EGFR mutation frequencies in two phase II studies of osimertinib (AURA extension and AURA2). Methods After progression while receiving their latest line of therapy, patients with EGFR mutation–positive advanced NSCLC provided tumor samples for mandatory central T790M testing for the study selection criteria. Tumor tissue mutation analysis for patient selection was performed with the Roche cobas EGFR Mutation Test (European Conformity–in vitro diagnostic, labeled investigational use only) (Roche Molecular Systems, Pleasanton, CA). Patients should not have been prescreened for T790M mutation status. The cobas test results were compared with those of the MiSeq next-generation sequencing system (Illumina, San Diego, CA), which was used as a reference method. Results Samples from 324 and 373 patients screened for AURA extension and AURA2, respectively, produced valid cobas test results. The T790M detection rates were similar between AURA extension and AURA2 (64% and 63%, respectively). The pooled T790M rate was 63%, with no difference by ethnicity (63% for Asian and non-Asian patients alike) or immediately prior treatment with an EGFR TKI (afatinib, 69%; erlotinib, 69%; and gefitinib, 63%). A higher proportion of patients had T790M detected against a background of exon 19 deletions versus L858R mutation (73% versus 58% [p = 0.0002]). In both trials the cobas test demonstrated high sensitivity (positive percent agreement) and specificity (negative percent agreement) for T790M detection when compared with the next-generation sequencing reference method: positive percent agreement of 91% versus 89% and negative percent agreement of 97% versus 98%. Conclusions In both trials, the rate of detection of T790M mutation in patients with advanced NSCLC was approximately 63% and was unaffected by immediately prior treatment with an EGFR TKI or ethnicity. ? 2017 International Association for the Study of Lung Cancer
Subjects
EGFR mutation; Non–small cell lung cancer; Osimertinib; T790M; Tyrosine kinase inhibitor
SDGs
Other Subjects
afatinib; erlotinib; gefitinib; osimertinib; protein tyrosine kinase inhibitor; antineoplastic agent; EGFR protein, human; epidermal growth factor receptor; osimertinib; piperazine derivative; protein kinase inhibitor; adult; Article; Asian; controlled study; disease course; EGFR gene; ethnicity; exon; gene; human; human tissue; major clinical study; mutation rate; mutational analysis; next generation sequencing; non small cell lung cancer; patient selection; phase 2 clinical trial; priority journal; prospective study; sensitivity and specificity; young adult; antagonists and inhibitors; clinical trial; disease exacerbation; enzymology; genetics; lung tumor; multicenter study; mutation; non small cell lung cancer; pathology; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Disease Progression; Humans; Lung Neoplasms; Mutation; Piperazines; Prospective Studies; Protein Kinase Inhibitors; Receptor, Epidermal Growth Factor
Publisher
Elsevier Inc
Type
journal article