EGFR T790M mutation testing within the osimertinib AURA Phase I study

Autor: Helen Brown, Kenneth S. Thress, Mireille Cantarini, Simon Dearden, Suzanne Jenkins, Rebecca Cole, Pasi A. Jänne, Malcolm R Ranson
Rok vydání: 2017
Předmět:
0301 basic medicine
Pulmonary and Respiratory Medicine
Oncology
Cancer Research
medicine.medical_specialty
Lung Neoplasms
Concordance
DNA Mutational Analysis
Antineoplastic Agents
Bioinformatics
Piperazines
03 medical and health sciences
symbols.namesake
T790M
0302 clinical medicine
Japan
Carcinoma
Non-Small-Cell Lung
Internal medicine
medicine
Humans
Osimertinib
Pathology
Molecular
Neoplasm Staging
Observer Variation
Sanger sequencing
Acrylamides
Aniline Compounds
business.industry
Reproducibility of Results
Microarray Analysis
Resistance mutation
United States
respiratory tract diseases
ErbB Receptors
030104 developmental biology
Drug Resistance
Neoplasm
030220 oncology & carcinogenesis
Mutation
Mutation (genetic algorithm)
Mutation testing
symbols
Laboratories
business
Companion diagnostic
Zdroj: Lung Cancer. 109:9-13
ISSN: 0169-5002
DOI: 10.1016/j.lungcan.2017.04.011
Popis: 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.
Databáze: OpenAIRE
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