EGFR T790M mutation testing within the osimertinib AURA Phase I study. (July 2017)

• Record Type: Journal Article
• Authors: Dearden, Simon; Brown, Helen; Jenkins, Suzanne; Thress, Kenneth S.; Cantarini, Mireille; Cole, Rebecca; Ranson, Malcolm; Jänne, Pasi A.
• Is Part Of: Lung cancer. Volume 109(2017)
• Page Start: 9
• Page End: 13
• Publication Date: 2017-07
• Subjects: EGFR epidermal growth factor receptor -- TKI tyrosine kinase inhibitor -- ARMS Amplification Refractory Mutation System -- PNA peptide nucleic acid -- NGS Next Generation Sequencing -- PCR polymerase chain reaction -- FFPET formalin-fixed, paraffin-embedded tissue -- H&E hematoxylin and eosin -- CNB core needle biopsies -- LoD limit of detection; EGFR genes -- Non-small cell lung cancer -- Osimertinib -- Protein kinase inhibitors; Lungs -- Cancer -- Periodicals; Lung Neoplasms -- Abstracts; Lung Neoplasms -- Periodicals; Poumons -- Cancer -- Périodiques; Lungs -- Cancer; Periodicals; Electronic journals; Electronic journals; 616.99424
• DOI: 10.1016/j.lungcan.2017.04.011
• Languages: English
• ISSNs: 0169-5002

Abstract

Highlights: The cobas ® EGFR Mutation Test proved to be a reliable testing platform. It demonstrated greater sensitivity compared with conventional Sanger sequencing. There was strong concordance between local and central laboratory results. Abstract: Objectives: Reliable epidermal growth factor receptor (EGFR) mutation testing techniques are required to identify eligible patients with EGFR mutation/T790M positive advanced non-small cell lung cancer (NSCLC), for treatment with osimertinib (AZD9291), an oral, potent, irreversible EGFR tyrosine kinase inhibitor (TKI) selective for EGFR-TKI-sensitizing and T790M resistance mutations over wild-type EGFR. There is no current consensus regarding the best method to detect EGFR T790M mutations. The aim of this study was to describe the concordance between local testing, which used a variety of methods, and central testing, using the cobas ® EGFR Mutation Test, for EGFR-sensitizing mutations and the T790M resistance mutation. Materials and methods: Tumor samples were obtained from all patients screened for inclusion onto the osimertinib Phase I expansion component of the AURA Phase I/II study (NCT01802632). Samples underwent central laboratory testing for EGFR-sensitizing mutations and T790M resistance mutation using the cobas ® EGFR Mutation Test. Results were compared with local laboratory test results, based on other testing methodologies including Sanger sequencing, therascreen ®, PNAClamp™, and Sequenom MassARRAY ® . Results: Central laboratory testing was successful in 99% of samples passing histopathology review and testing success rates were comparable across the three central laboratories. Concordance between central and local testing for common sensitizing mutations was high (>98%) and concordance for the T790M mutation was also high (>90%). Tumor heterogeneity, along with other technical factors may have influenced this result. Conclusions: Within the osimertinib AURA Phase I study, EGFR mutation testing across three centralized laboratories using the cobas ® EGFR Mutation Test was feasible and successful, with strong concordance between local and central laboratory results, including for T790M. The cobas ® EGFR Mutation Test has subsequently been approved as the companion diagnostic test for osimertinib in the USA and Japan.