Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy

Di Fiore, F; Blanchard, F; Charbonnier, F; Le Pessot, F; Lamy, A; Galais, M P; Bastit, L; Killian, A; Sesboüé, R; Tuech, J J; Queuniet, A M; Paillot, B; Sabourin, J C; Michot, F; Michel, P; Frebourg, T

doi:10.1038/sj.bjc.6603685

Cited by 734Colorectal Cancer Treatments and StudiesLung Cancer Treatments and MutationsGenetic factors in colorectal cancer

Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy

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Di Fiore, F, Blanchard, F, Charbonnier, F, Le Pessot, F, Lamy, A, Galais, M P, Bastit, L, Killian, A +8 more·2007·British Journal of Cancer

DOI 10.1038/sj.bjc.6603685PMC PMC2360149

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Abstract

The predictive value of KRAS mutation in metastatic colorectal cancer (MCRC) patients treated with cetuximab plus chemotherapy has recently been suggested. In our study, 59 patients with a chemotherapy-refractory MCRC treated with cetuximab plus chemotherapy were included and clinical response was evaluated according to response evaluation criteria in solid tumours (RECIST). Tumours were screened for KRAS mutations using first direct sequencing, then two sensitive methods based on SNaPshot and PCR-ligase chain reaction (LCR) assays. Clinical response was evaluated according to gene mutations using the Fisher exact test. Times to progression (TTP) were calculated using the Kaplan-Meier method and compared with log-rank test. A KRAS mutation was detected in 22 out of 59 tumours and, in six cases, was missed by sequencing analysis but detected using the SNaPshot and PCR-LCR assays. Remarkably, no KRAS mutation was found in the 12 patients with clinical response. KRAS mutation was associated with disease progression (P=0.0005) and TTP was significantly decreased in mutated KRAS patients (3 vs 5.5 months, P=0.015). Our study confirms that KRAS mutation is highly predictive of a non-response to cetuximab plus chemotherapy in MCRC and highlights the need to use sensitive molecular methods, such as SNaPshot or PCR-LCR assays, to ensure an efficient mutation detection.

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KRAS exon 2 mutations are major determinants of primary resistance to cetuximab or panitumumab.
“as major determinants of primary resistance to cetuximab or panitumumab [17, 27-29].”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [28]

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KRAS mutation is highly predictive of cetuximab resistance in metastatic colorectal cancer
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Self-citation
Predictive and prognostic value of KRAS mutations in metastatic colorectal cancer patients treated with cetuximab: A meta-analysis of 22 studies
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[Analysis of the correlation with KRAS gene mutation status and the benefit of cetuximab plus irinotecan as third- line chemotherapy for the Treatment of unresectable metastatic colorectal cancer].
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KRAS mutations in colorectal cancer is a predictive factor of response and progression free survival in patients treated with Cetuximab.
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Authors: Di Fiore, F., Blanchard, F., Charbonnier, F., Le Pessot, F., Lamy, A., Galais, M. P., Bastit, L., Killian, A., Sesboüé, R., Tuech, J. J., Queuniet, A. M., Paillot, B., Sabourin, J. C., Michot, F., Michel, P., & Frebourg, T.
Affiliations: Centre Hospitalier Universitaire de Rouen (FR)
Inserm (FR)
Centre Hospitalier Universitaire de Caen Normandie (FR)
ORCID: Galais, M P
Killian, A
Tuech, J J
Sabourin, J C
Michel, P
Venue: British Journal of Cancer
Publisher: Springer Science and Business Media LLC
Published: 2007-03-20
Volume: 96
Issue: 8
Pages: 1166-1169
ISSN: 0007-0920 (ISSN-L)
1532-1827
DOI: 10.1038/sj.bjc.6603685
PMC: PMC2360149
OpenAlex: W1999250974
Cited by: 734
References: 12
Citations by year: 2025: 6 · 2024: 6 · 2023: 10 · 2022: 10 · 2021: 8 · 2020: 15 · 2019: 14 · 2018: 14 · 2017: 21 · 2016: 30 · 2015: 33 · 2014: 54 · 2013: 52 · 2012: 62
FWCI: 51.47
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
www.springer.com/tdm (unspecified)
Locations: British Journal of Cancer (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: Institut National Du Cancer
Topics: Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
Keywords: KRAS mutation, metastatic colorectal cancer, cetuximab, anti-EGFR therapy, predictive biomarkers, chemotherapy-refractory cancer, SNaPshot assay, mutation detection sensitivity, time to progression, clinical response
MeSH terms: Cetuximab, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Humans, Mutation, Neoplasm Metastasis, Genes, ras, Colorectal Neoplasms, Polymerase Chain Reaction, Antibodies, Monoclonal, Humanized, ErbB Receptors

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Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy

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