Cited by 522Colorectal Cancer Treatments and StudiesMonoclonal and Polyclonal Antibodies ResearchLung Cancer Treatments and Mutations

Impact of FcγRIIa-FcγRIIIa Polymorphisms and KRAS Mutations on the Clinical Outcome of Patients With Metastatic Colorectal Cancer Treated With Cetuximab Plus Irinotecan

Bibeau, Frédéric, Lopez-Crapez, Evelyne, Di Fiore, Frédéric, Thezenas, Simon, Ychou, Marc, Blanchard, France, Lamy, Aude, Penault-Llorca, Frédérique +4 more·2009·Journal of Clinical Oncology

Abstract

Purpose: The antiepidermal growth factor receptor antibody cetuximab shows activity in irinotecan-refractory metastatic colorectal cancer (mCRC), mainly in wild-type KRAS tumors. Cetuximab may also exert antitumor effects through antibody-dependent cell-mediated cytotoxicity (ADCC) in which antibody Fc portion interacts with Fc receptors (FcγRs) expressed by immune cells. ADCC is influenced by FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms that are clinically relevant in follicular lymphoma and metastatic breast cancer treated with rituximab and trastuzumab, respectively. We investigated the association of FcγR polymorphisms and KRAS mutation with the outcome of irinotecan-refractory mCRC patients treated with cetuximab plus irinotecan. Patients and Methods: Tumor and normal tissues from 69 patients were screened for KRAS mutations using a sensitive multiplex assay and genotyped for FcγRIIa and FcγRIIIa polymorphisms by direct sequencing and multiplex allele-specific polymerase chain reaction, respectively. The results were correlated with response and progression-free survival (PFS). Results: KRAS mutations were associated with lower response rate (4% v 27% in nonmutated patients; P = .021) and shorter PFS (3.0 v 5.3 months; P = .021). Patients with FcγRIIa-131H/H and/or FcγIIIa-158V/V genotypes had longer PFS than 131R and 158F carriers (5.5 v 3.0 months; P = .005). The difference remained significant for mutated-KRAS patients. By multivariate analysis, KRAS mutation and FcγR combined status were independent risk factors for PFS. Conclusion: Combined FcγRIIa/FcγRIIIa polymorphisms are prognostic factors for disease progression in mCRC patients treated with cetuximab plus irinotecan. As these polymorphisms are also clinically relevant in mutated-KRAS mCRC, an important role of ADCC in cetuximab efficacy is presumed.

Integrity signals

Registry

Crossref · 10.1200/jco.2008.18.0463

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Bibeau, F., Lopez-Crapez, E., Di Fiore, F., Thezenas, S., Ychou, M., Blanchard, F., Lamy, A., Penault-Llorca, F., Frébourg, T., Michel, P., Sabourin, J.-C., & Boissière-Michot, F.
Affiliations
  • Inserm (FR)
  • From the Departments of Pathology, Biology, Biostatistics, and Oncology, Centre Régional de Lutte Contre le Cancer Val d'Aurelle-Paul Lamarque, Montpellier; Digestive Oncology Unit, Department of Gastroenterology, Rouen University Hospital; Inserm U614, Faculty of Medicine; Department of Pathology, Rouen University Hospital; and the Department of Pathology, Centre Jean Perrin, Clermont-Ferrand, France.
Venue
Journal of Clinical Oncology
Published
2009-03-01
Volume
27
Issue
7
Pages
1122-1129
ISSN
  • 0732-183X (ISSN-L)
  • 1527-7755
OpenAlex
W2122618533
Cited by
521
References
44
Citations by year
2026: 3 · 2025: 13 · 2024: 12 · 2023: 19 · 2022: 16 · 2021: 17 · 2020: 24 · 2019: 16 · 2018: 26 · 2017: 24 · 2016: 32 · 2015: 40 · 2014: 41 · 2013: 46 · 2012: 53
FWCI
31.59
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Clinical Oncology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Keywords
FcγRIIIa, Fc receptor polymorphism, KRAS mutation, cetuximab, irinotecan, metastatic colorectal cancer, antibody-dependent cellular cytotoxicity, progression-free survival, prognostic factors, irinotecan-refractory disease, epidermal growth factor receptor
MeSH terms
Cetuximab, Irinotecan, Antibodies, Monoclonal, Antibody-Dependent Cell Cytotoxicity, Antineoplastic Combined Chemotherapy Protocols, Camptothecin, Female, Humans, Male, Middle Aged, Mutation, Polymorphism, Genetic, Proto-Oncogene Proteins, Retrospective Studies, Colorectal Neoplasms, Multivariate Analysis, Proportional Hazards Models, Survival Analysis, Proto-Oncogene Proteins p21(ras), Receptors, IgG, Disease-Free Survival, ras Proteins, Drug Resistance, Neoplasm, Antibodies, Monoclonal, Humanized

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review