KRAS wild-type state predicts survival and is associated to early radiological response in metastatic colorectal cancer treated with cetuximab
Open accessAbstract
Background KRAS mutation status is a candidate marker for predicting survival in patients with metastatic colorectal cancer (mCRC) treated with cetuximab (CTX).Patients and methods We studied the KRAS mutation status of 113 patients with irinotecan refractory mCRC treated with CTX in clinical trials. A predictive model for objective response (OR), progression-free survival (PFS) and overall survival (OS) was constructed using logistic and Cox regression.Results OR was seen in 27 of 66 KRAS wild-type (WT) patients versus 0 of 42 in KRAS mutants. Median OS was significantly better in KRAS WT versus mutants (43.0 versus 27.3 weeks; P = 0.020). Decrease in tumor sizes was significantly larger at all time points in WT patients. KRAS WT patients with an initial relative decrease of tumor size >9.66% at week 6 had a significantly better median OS compared with all other patients (74.9 versus 30.6 weeks; P = 0.0000025). Within KRAS WT patients OS was significantly better in patients with an initial decrease compared with those without [median OS: 74.9 versus 30.6 weeks (P = 0.00000012)].Conclusions KRAS WT status is associated to survival benefit in CTX treated mCRC. This benefit is even more pronounced in those patients with early radiological response. These characteristics may be exploited for response prediction.
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KRAS mutation is a predictive biomarker for resistance to cetuximab in metastatic colorectal cancer.
“KRAS mutation is a predictive biomarker for resistance to cetuximab (Erbitux®) in metastatic colorectal cancer (mCRC).”
From Dasatinib sensitizes KRAS mutant colorectal tumors to cetuximab (2011) · cites this paper as De Roock et al., 2008
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- Authors
- De Roock, W., Piessevaux, H., De Schutter, J., Janssens, M., De Hertogh, G., Personeni, N., Biesmans, B., Van Laethem, J.-L., Peeters, M., Humblet, Y., Van Cutsem, E., & Tejpar, S.
- Affiliations
- Cliniques Universitaires Saint-Luc (BE)
- KU Leuven (BE)
- Ghent University Hospital (BE)
- Corresponding author
- Tejpar, S.
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 19
- Issue
- 3
- Pages
- 508-515
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2098223440
- Cited by
- 827
- References
- 17
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 7 · 2023: 15 · 2022: 16 · 2021: 18 · 2020: 19 · 2019: 22 · 2018: 11 · 2017: 22 · 2016: 26 · 2015: 49 · 2014: 70 · 2013: 65 · 2012: 67
- FWCI
- 53.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Digital Access to Libraries (submittedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Fonds Wetenschappelijk Onderzoek
- Universiteit Gent
- Vlaamse regering
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- KRAS wild-type, KRAS mutation status, metastatic colorectal cancer, cetuximab, predictive biomarkers, objective response, radiological response, progression-free survival, overall survival, irinotecan-refractory disease, tumor shrinkage
- MeSH terms
- Cetuximab, Irinotecan, Antibodies, Monoclonal, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Camptothecin, Female, Humans, Male, Middle Aged, Mutation, Proto-Oncogene Proteins, Retrospective Studies, Sensitivity and Specificity, Tomography, X-Ray Computed, Colorectal Neoplasms, Survival Rate, Logistic Models, Proportional Hazards Models, Proto-Oncogene Proteins p21(ras), Disease-Free Survival, ras Proteins, Antibodies, Monoclonal, Humanized
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