Clinical Validation of a PCR Assay for the Detection of EGFR Mutations in Non-Small-Cell Lung Cancer : Retrospective Testing of Specimens from the EURTAC Trial
Benlloch, Susana (Pangaea Biotech)
Botero, Maria Luisa (Pangaea Biotech)
Beltran-Alamillo, Jordi (Pangaea Biotech)
Mayo, Clara (Pangaea Biotech)
Giménez-Capitán, Ana (Pangaea Biotech)
de Aguirre, Itziar (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Queralt, C (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ramirez, Jose Luis (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Ramón y Cajal, Santiago (Universitat Autònoma de Barcelona. Departament de Ciències Morfològiques)
Klughammer, Barbara (F. Hoffmann-La Roche, Basel)
Schlegel, Mariette (F. Hoffmann-La Roche, Basel)
Bordogna, Walter (F. Hoffmann-La Roche, Basel)
Chen, David (Genentech, South San Francisco, California)
Zhang, Guili (Roche Molecular Systems, Pleasanton, California)
Kovach, Barbara (Roche Molecular Systems, Pleasanton, California)
Shieh, Felice (Roche Molecular Systems, Pleasanton, California)
Palma, John F. (Roche Molecular Systems, Pleasanton, California)
Wu, Lin (Roche Molecular Systems, Pleasanton, California)
Lawrence, H. Jeffrey (Roche Molecular Systems, Pleasanton, California)
Taron, Miquel (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)

Date:	2014
Abstract:	The EURTAC trial demonstrated that the tyrosine kinase inhibitor (TKI) erlotinib was superior to chemotherapy as first-line therapy for advanced non-small cell lung cancers (NSCLC) that harbor EGFR activating mutations in a predominantly Caucasian population. Based on EURTAC and several Asian trials, anti- EGFR TKIs are standard of care for EGFR mutation-positive NSCLC. We sought to validate a rapid multiplex EGFR mutation assay as a companion diagnostic assay to select patients for this therapy. Samples from the EURTAC trial were prospectively screened for EGFR mutations using a combination of laboratory-developed tests (LDTs), and tested retrospectively with the cobas EGFR mutation test (EGFR PCR test). The EGFR PCR test results were compared to the original LDT results and to Sanger sequencing, using a subset of specimens from patients screened for the trial. Residual tissue was available from 487 (47%) of the 1044 patients screened for the trial. The EGFR PCR test showed high concordance with LDT results with a 96. 3% overall agreement. The clinical outcome of patients who were EGFR -mutation detected by the EGFR PCR test was very similar to the entire EURTAC cohort. The concordance between the EGFR PCR test and Sanger sequencing was 90. 6%. In 78. 9% of the discordant samples, the EGFR PCR test result was confirmed by a sensitive deep sequencing assay. This retrospective study demonstrates the clinical utility of the EGFR PCR test in the accurate selection of patients for anti- EGFR TKI therapy. The EGFR PCR test demonstrated improved performance relative to Sanger sequencing.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 9 (february 2014) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0089518
PMID: 24586842

8 p, 334.2 KB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
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