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Cited by 163Colorectal Cancer Treatments and StudiesGenetic factors in colorectal cancerLung Cancer Treatments and Mutations

Prevalence of RAS mutations and individual variation patterns among patients with metastatic colorectal cancer: A pooled analysis of randomised controlled trials

Peeters, M., Kafatos, G., Taylor, A., Gastanaga, V.M., Oliner, K.S., Hechmati, G., Terwey, J.-H., van Krieken, J.H.·2015·European Journal of Cancer
DOI 10.1016/j.ejca.2015.05.017
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Abstract

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.

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  • KRAS is the most dominant mutated subtype in the RAS family and is responsible for 85% of RAS gene-driven cancers, particularly in pancreatic, colorectal, and lung cancers.

    “It is the most dominant mutated subtype in the RAS family and is responsible for 85% of RAS gene-driven cancers, particularly in pancreatic, colorectal, and lung cancers.40–42”

    From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [42]

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Authors
Peeters, M., Kafatos, G., Taylor, A., Gastanaga, V. M., Oliner, K. S., Hechmati, G., Terwey, J.-H., & van Krieken, J. H.
Affiliations
  • Antwerp University Hospital (BE)
  • Amgen (United Kingdom) (GB)
  • Amgen (United States) (US)
  • Amgen (Switzerland) (CH)
Corresponding author
Peeters, M.
ORCID
Venue
European Journal of Cancer
Publisher
Elsevier BV
Published
2015-09
Volume
51
Issue
13
Pages
1704-1713
ISSN
0959-8049 (ISSN-L)
DOI
10.1016/j.ejca.2015.05.017
OpenAlex
W1845370611
Cited by
163
References
29
Citations by year
2026: 3 · 2025: 8 · 2024: 11 · 2023: 20 · 2022: 13 · 2021: 19 · 2020: 17 · 2019: 19 · 2018: 13 · 2017: 26 · 2016: 12 · 2015: 2
FWCI
7.72
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • European Journal of Cancer (publishedVersion)
  • PubMed (publishedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
Amgen Ltd
Topics
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords
RAS mutations, KRAS, NRAS, metastatic colorectal cancer, EGFR inhibitors, panitumumab, KRAS exon 2
MeSH terms
Panitumumab, Adolescent, Adult, Aged, Antibodies, Monoclonal, Antineoplastic Agents, DNA Mutational Analysis, Exons, Female, Gene Frequency, Humans, Male, Membrane Proteins, Middle Aged, Mutation, Neoplasm Metastasis, Phenotype, Predictive Value of Tests, Retrospective Studies, Biomarkers, Tumor, Colorectal Neoplasms, Randomized Controlled Trials as Topic, Proto-Oncogene Proteins p21(ras), Clinical Trials, Phase I as Topic, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, Patient Selection, Genetic Predisposition to Disease, GTP Phosphohydrolases, Proto-Oncogene Proteins B-raf, Young Adult, Precision Medicine, Molecular Targeted Therapy

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