Document Detail

Validation of Companion Diagnostic for Detection of Mutations in Codons 12 and 13 of the KRAS Gene in Patients with Metastatic Colorectal Cancer: Analysis of the NCIC CTG CO.17 Trial.
MedLine Citation:
PMID:  23030695     Owner:  NLM     Status:  Publisher    
Context.- The therascreen KRAS RGQ PCR kit is being developed as a companion diagnostic to aid clinicians, through detection of KRAS mutations, in the identification of patients with metastatic colorectal cancer (mCRC) who are more likely to benefit from cetuximab. Objective.- To assess whetherKRASmutation status, determined by using the therascreen KRAS kit, is a predictive marker of cetuximab efficacy. Design.- Tissue samples were obtained from patients with mCRC treated on the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) CO.17 phase 3 study of cetuximab plus best supportive care (BSC) versus BSC alone. Tumor DNA samples were assessed for the presence of KRAS mutations by using the therascreen KRAS kit. Efficacy and safety were assessed to determine whether mutation status was predictive of outcomes. Results.- Evaluable samples were available from 453 patients (79.2%) enrolled in the NCIC CTG CO.17 trial. The KRAS wild-type subset represented 54.1% (245 of 453) of the evaluated population. Median overall survival of patients with KRAS wild-type tumors was 8.6 months among those who received cetuximab plus BSC and 5.0 months among patients who received BSC alone (hazard ratio [HR], 0.63; P = .002). Among patients with KRAS mutant mCRC, no meaningful difference in overall survival was observed between arms (HR, 0.91; P = .55). These results are consistent with a previous report that analyzed patient tumor samples by using bidirectional sequencing. Conclusions.- These data support the utility of the therascreen KRAS kit as a means of selecting patients who may benefit from cetuximab therapy.
Christopher T Harbison; Christine E Horak; Jean-Marie Ledeine; Pralay Mukhopadhyay; Daniel P Malone; Chris O'Callaghan; Derek J Jonker; Christos S Karapetis; Shirin Khambata-Ford; Nancy Gustafson; Ovidiu C Trifan; Shao-Chun Chang; Paul Ravetto; George A Green
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-3
Journal Detail:
Title:  Archives of pathology & laboratory medicine     Volume:  -     ISSN:  1543-2165     ISO Abbreviation:  Arch. Pathol. Lab. Med.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7607091     Medline TA:  Arch Pathol Lab Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
From Clinical Biomarkers, Oncology (Drs Harbison, Horak, Khambata-Ford, and Mr Malone), Global Biometric Sciences, Oncology (Drs Mukhopadhyay and Gustafson), Global Clinical Research, Oncology (Dr Trifan), and Center for Pharmacodiagnostics (Dr Green), Bristol-Myers Squibb Research and Development, Princeton, New Jersey; Biostatistics, Bristol-Myers Squibb Research and Development, Braine l'Alleud, Belgium (Dr Ledeine); Clinical Trials Group, National Cancer Institute of Canada, Kingston, Ontario, Canada (Dr O'Callaghan); Department of Medical Oncology, Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada (Dr Jonker); Department of Medical Oncology, Flinders Medical Centre and Flinders University, Adelaide, Australia (Dr Karapetis); Oncology Business Unit, Eli Lilly and Company, Indianapolis, Indiana (Dr Chang); and Operations Europe, QIAGEN, Manchester, United Kingdom (Mr Ravetto). Dr Khambata-Ford is now with Oncology Correlative Science at Novartis Pharmaceuticals Corporation, East Hanover, New Jersey. Dr Gustafson is now with Biostatistics and Statistical Programming at Alcon, a Novartis company, Fort Worth, Texas.
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