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EGFR Mutation Analysis for Prospective Patient Selection in Two Phase II Registration Studies of Osimertinib.
Jenkins, Suzanne; Yang, James Chih-Hsin; Jänne, Pasi A; Thress, Kenneth S; Yu, Karen; Hodge, Rachel; Weston, Susie; Dearden, Simon; Patel, Sabina; Cantarini, Mireille; Shepherd, Frances A.
Afiliação
  • Jenkins S; AstraZeneca, Macclesfield, United Kingdom. Electronic address: Suzanne.Jenkins@astrazeneca.com.
  • Yang JC; National Taiwan University Hospital, National Taiwan University Cancer Center, Taipei City, Republic of China.
  • Jänne PA; Dana-Farber Cancer Institute, Boston, Massachusetts.
  • Thress KS; AstraZeneca, Waltham, Massachusetts.
  • Yu K; Roche Molecular Systems, Inc., Pleasanton, California.
  • Hodge R; AstraZeneca, Cambridge, United Kingdom.
  • Weston S; AstraZeneca, Alderley Park, United Kingdom.
  • Dearden S; AstraZeneca, Macclesfield, United Kingdom.
  • Patel S; AstraZeneca, Cambridge, United Kingdom.
  • Cantarini M; AstraZeneca, Alderley Park, United Kingdom.
  • Shepherd FA; Princess Margaret Cancer Centre, Toronto, Canada.
J Thorac Oncol ; 12(8): 1247-1256, 2017 08.
Article em En | MEDLINE | ID: mdl-28527899
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piperazinas / Carcinoma Pulmonar de Células não Pequenas / Inibidores de Proteínas Quinases / Receptores ErbB / Neoplasias Pulmonares / Mutação / Antineoplásicos Tipo de estudo: Clinical_trials / Observational_studies Limite: Humans Idioma: En Revista: J Thorac Oncol Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piperazinas / Carcinoma Pulmonar de Células não Pequenas / Inibidores de Proteínas Quinases / Receptores ErbB / Neoplasias Pulmonares / Mutação / Antineoplásicos Tipo de estudo: Clinical_trials / Observational_studies Limite: Humans Idioma: En Revista: J Thorac Oncol Ano de publicação: 2017 Tipo de documento: Article