Cited by 673Colorectal Cancer Treatments and StudiesLung Cancer Treatments and MutationsGenetic factors in colorectal cancer

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Analysis of PTEN , BRAF , and EGFR Status in Determining Benefit From Cetuximab Therapy in Wild-Type KRAS Metastatic Colon Cancer

Laurent-Puig, Pierre, Cayre, Anne, Manceau, Gilles, Buc, Emmanuel, Bachet, Jean-Baptiste, Lecomte, Thierry, Rougier, Philippe, Lievre, Astrid, Landi, Bruno, Boige, Valérie, Ducreux, Michel, Ychou, Marc, Bibeau, Fréderic, Bouché, Olivier, Reid, Julia, Stone, Steven, Penault-Llorca, Frédérique·2009·Journal of Clinical Oncology

DOI 10.1200/jco.2008.21.6796

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Abstract

Purpose: The occurrence of KRAS mutation is predictive of nonresponse and shorter survival in patients treated by anti–epidermal growth factor receptor (anti-EGFR) antibody for metastatic colorectal cancer (mCRC), leading the European Medicine Agency to limit its use to patients with wild-type KRAS tumors. However, only half of these patients will benefit from treatment, suggesting the need to identify additional biomarkers for cetuximab-based treatment efficacy. Patients and Methods: We retrospectively collected tumors from 173 patients with mCRC. All but one patient received a cetuximab-based regimen as second-line or greater therapy. KRAS and BRAF status were assessed by allelic discrimination. EGFR amplification was assessed by chromogenic in situ hybridization and fluorescent in situ hybridization, and the expression of PTEN was assessed by immunochemistry. Results: In patients with KRAS wild-type tumors (n = 116), BRAF mutations (n = 5) were weakly associated with lack of response (P = .063) but were strongly associated with shorter progression-free survival (P < .001) and shorter overall survival (OS; P < .001). A high EGFR polysomy or an EGFR amplification was found in 17.7% of the patients and was associated with response (P = .015). PTEN null expression was found in 19.9% of the patients and was associated with shorter OS (P = .013). In multivariate analysis, BRAF mutation and PTEN expression status were associated with OS. Conclusion: BRAF status, EGFR amplification, and cytoplasmic expression of PTEN were associated with outcome measures in KRAS wild-type patients treated with a cetuximab-based regimen. Subsequent studies in clinical trial cohorts will be required to confirm the clinical utility of these markers.

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Authors: Laurent-Puig, P., Cayre, A., Manceau, G., Buc, E., Bachet, J.-B., Lecomte, T., Rougier, P., Lievre, A., Landi, B., Boige, V., Ducreux, M., Ychou, M., Bibeau, F., Bouché, O., Reid, J., Stone, S., & Penault-Llorca, F.
Affiliations: From the Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) -S775 Molecular Basis of Xenobiotics Response; Université Paris Descartes; Assistance Publique–Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Hôpital Ambroise Paré, Paris; Centre Jean Perrin, Université d'Auvergne Equipe Associée EA4233 Centre Hospitalier Universitaire (CHU), Clermont-Ferrand; CHU, Tours; Institut Gustave Roussy, Villejuif; Centre Régional de Lutte contre le Cancer (CRLC) Val...
Inserm (FR)
ORCID: Cayre, Anne
Manceau, Gilles
Buc, Emmanuel
Bachet, Jean-Baptiste
Lecomte, Thierry
Boige, Valérie
Ducreux, Michel
Ychou, Marc
Bouché, Olivier
Stone, Steven
Venue: Journal of Clinical Oncology
Publisher: American Society of Clinical Oncology (ASCO)
Published: 2009-12-10
Volume: 27
Issue: 35
Pages: 5924-5930
ISSN: 0732-183X (ISSN-L)
1527-7755
DOI: 10.1200/jco.2008.21.6796
OpenAlex: W2125229905
Cited by: 673
References: 39
Citations by year: 2026: 2 · 2025: 10 · 2024: 16 · 2023: 6 · 2022: 10 · 2021: 22 · 2020: 16 · 2019: 27 · 2018: 26 · 2017: 32 · 2016: 45 · 2015: 55 · 2014: 81 · 2013: 73 · 2012: 85
FWCI: 41.77
Type: journal article
Language: en
Open access: closed
Locations: Journal of Clinical Oncology (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion)
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: cetuximab, metastatic colorectal cancer, KRAS wild-type, BRAF mutation, PTEN expression, EGFR amplification, predictive biomarkers, anti-EGFR antibody therapy, progression-free survival, overall survival, treatment response
MeSH terms: Cetuximab, Antibodies, Monoclonal, Antineoplastic Agents, France, Gene Amplification, Humans, Immunohistochemistry, Mutation, Predictive Value of Tests, Proto-Oncogene Proteins, Retrospective Studies, Time Factors, Biomarkers, Tumor, Colorectal Neoplasms, Gene Expression Regulation, Neoplastic, Proportional Hazards Models, Proto-Oncogene Proteins p21(ras), Treatment Outcome, In Situ Hybridization, In Situ Hybridization, Fluorescence, Risk Assessment, Disease-Free Survival, Patient Selection, ras Proteins, Proto-Oncogene Proteins B-raf, PTEN Phosphohydrolase, Kaplan-Meier Estimate, Precision Medicine, Antibodies, Monoclonal, Humanized, ErbB Receptors

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Analysis of PTEN , BRAF , and EGFR Status in Determining Benefit From Cetuximab Therapy in Wild-Type KRAS Metastatic Colon Cancer

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