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Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by Cetuximab plus chemotherapy
Open accessAbstract
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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“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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Metadata
- 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)
- Venue
- British Journal of Cancer
- Published
- 2007-03-20
- Volume
- 96
- Issue
- 8
- Pages
- 1166-1169
- ISSN
- 0007-0920 (ISSN-L)
- 1532-1827
- 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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