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Title
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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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Author
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Abstract
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| 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. (C) 2015 Published by Elsevier Ltd. |
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Language
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English
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Source (journal)
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European journal of cancer. - Oxford, 1990, currens
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Publication
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Oxford
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2015
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ISSN
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0959-8049
[print]
1879-0852
[online]
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DOI
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10.1016/J.EJCA.2015.05.017
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Volume/pages
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51
:13
(2015)
, p. 1704-1713
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ISI
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000359007800007
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Pubmed ID
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26049686
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Full text (Publisher's DOI)
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Full text (publisher's version - intranet only)
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