دورية أكاديمية
Prevalence of RAS mutations and individual variation patterns among patients with metastatic colorectal cancer: A pooled analysis of randomised controlled trials.
| العنوان: | Prevalence of RAS mutations and individual variation patterns among patients with metastatic colorectal cancer: A pooled analysis of randomised controlled trials. |
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| المؤلفون: | Peeters M; Department of Oncology, Antwerp University Hospital, Wilrijkstraat 10, B-2650 Edegem, Belgium. Electronic address: Marc.Peeters@uza.be., Kafatos G; Center for Observational Research, Amgen Ltd, 1 Uxbridge Business Park, Sanderson Road, Uxbridge UB8 1DH, UK., Taylor A; Center for Observational Research, Amgen Ltd, 1 Uxbridge Business Park, Sanderson Road, Uxbridge UB8 1DH, UK., Gastanaga VM; Center for Observational Research, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91329-1799, USA., Oliner KS; Medical Sciences, Amgen Inc, One Amgen Center Drive, Thousand Oaks, CA 91329-1799, USA., Hechmati G; Health Economics, Amgen (Europe) GmbH, Dammstrasse 23, Opus 105, Zug 6301, Switzerland., Terwey JH; Medical Development, Amgen (Europe) GmbH, Zählerweg 6, Opus 192, Zug 6301, Switzerland., van Krieken JH; Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen (911), The Netherlands. |
| المصدر: | European journal of cancer (Oxford, England : 1990) [Eur J Cancer] 2015 Sep; Vol. 51 (13), pp. 1704-13. Date of Electronic Publication: 2015 Jun 03. |
| نوع المنشور: | Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Ltd Country of Publication: England NLM ID: 9005373 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0852 (Electronic) Linking ISSN: 09598049 NLM ISO Abbreviation: Eur J Cancer Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Elsevier Science Ltd Original Publication: Oxford ; New York : Pergamon Press, c1990- |
| مواضيع طبية MeSH: | Mutation*, Biomarkers, Tumor/*genetics , Colorectal Neoplasms/*genetics , GTP Phosphohydrolases/*genetics , Membrane Proteins/*genetics , Proto-Oncogene Proteins p21(ras)/*genetics, Adolescent ; Adult ; Aged ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/therapeutic use ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic ; Clinical Trials, Phase III as Topic ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/pathology ; DNA Mutational Analysis ; Exons ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Molecular Targeted Therapy ; Neoplasm Metastasis ; Panitumumab ; Patient Selection ; Phenotype ; Precision Medicine ; Predictive Value of Tests ; Proto-Oncogene Proteins B-raf/genetics ; Randomized Controlled Trials as Topic ; Retrospective Studies ; Young Adult |
| مستخلص: | Background: The use of epidermal growth factor receptor inhibitors to treat metastatic colorectal cancer (mCRC) patients requires prior confirmation of tumour wild type (WT) RAS mutation status (exons 2/3/4 for KRAS or NRAS). This retrospective pooled analysis aims to robustly estimate RAS mutation prevalence and individual variation patterns in mCRC patients. Method: Individual patient data from five randomised, controlled panitumumab studies (three phase III, one phase II and one phase Ib/II) were pooled for this analysis. The phase III studies included mCRC patients independent of RAS mutation status; the phase II and Ib/II studies included mCRC patients with confirmed WT KRAS exon 2 status. Four studies conducted RAS testing using Sanger sequencing; one study used a combination of next-generation sequencing and Sanger sequencing. In order to assign overall RAS status, the mutation status of all exons 2/3/4 KRAS or NRAS was required to be known. Results: Data from 3196 mCRC patients from 36 countries were included in the analysis. The overall unadjusted RAS mutation prevalence in mCRC patients was 55.9% (95% confidence interval (CI): [53.9-57.9%]), with the following distribution observed: KRAS exon 2 (prevalence 42.6% [40.7-44.5%]); KRAS exon 3 (3.8% [2.9-4.9%]); KRAS exon 4 (6.2% [5.0-7.6%]); NRAS exon 2 (2.9% [2.1-3.9%]); NRAS exon 3 (4.2% [3.2-5.4%]); NRAS exon 4 (0.3% [0.1-0.7%]). Differences in RAS mutation prevalence estimates were observed by study (p=0.001), gender (p=0.030), and by country (p=0.028). Conclusions: This analysis provides robust estimates of overall RAS mutation prevalence and individual variation patterns in mCRC patients. (Copyright © 2015. Published by Elsevier Ltd.) |
| فهرسة مساهمة: | Keywords: BRAF; KRAS; NRAS; Panitumumab; RAS prevalence; mCRC |
| سلسلة جزيئية: | ClinicalTrials.gov NCT00113763; NCT00339183; NCT00364013; NCT00788957; NCT00819780 |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) 0 (Antineoplastic Agents) 0 (Biomarkers, Tumor) 0 (KRAS protein, human) 0 (Membrane Proteins) 6A901E312A (Panitumumab) EC 2.7.11.1 (BRAF protein, human) EC 2.7.11.1 (Proto-Oncogene Proteins B-raf) EC 3.6.1.- (GTP Phosphohydrolases) EC 3.6.1.- (NRAS protein, human) EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras)) |
| تواريخ الأحداث: | Date Created: 20150608 Date Completed: 20160428 Latest Revision: 20220410 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.ejca.2015.05.017 |
| PMID: | 26049686 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1879-0852 |
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| DOI: | 10.1016/j.ejca.2015.05.017 |