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EGFR FISH assay predicts for response to cetuximab in chemotherapy refractory colorectal cancer patients
Open accessAbstract
Background Standardized conditions to distinguish subpopulations of colorectal cancer (CRC) patients more and less sensitive to cetuximab therapy remain undefined.Materials and methods We retrospectively analyzed epidermal growth factor receptor (EGFR) copy number by fluorescence in situ hybridization (FISH) in paraffin-embedded tumor blocks from 85 chemorefractory CRC patients treated with cetuximab. Results were analyzed according to different score systems previously reported in colorectal and lung cancers. The primary end point of the study was identification of the EGFR FISH score that best associates with response rate (RR).Results Using receiver operating characteristic (ROC) analysis, the cut-off that best discriminated responders versus nonresponders to cetuximab was a mean of 2.92 EGFR gene copies per cell. This model showed sensitivity of 58.6% [95% confidence interval (CI) = 47.1-70.1) and specificity of 93.3% (95% CI = 80.6-100). EGFR FISH-positive patients (N = 43, 50.6%) had significantly higher RR (P = 0.0001) and significantly longer time to disease progression (P = 0.02) than EGFR FISH negative (N = 42, 49.4%). Other scoring systems resulted less accurate in discriminating patients with the highest likelihood of response to cetuximab therapy.Conclusions CRC patients with high EGFR gene copy number have an increased likelihood to respond to cetuximab therapy. Prospective clinical trials with a careful standardization of assay conditions and pattern interpretation are urgently needed.
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“Increased EGFR gene copy number could predict response among KRAS wild-type patients [53, 91, 111-113]”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [113]
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Metadata
- Authors
- Cappuzzo, F., Finocchiaro, G., Rossi, E., Jänne, P. A., Carnaghi, C., Calandri, C., Bencardino, K., Ligorio, C., Ciardiello, F., Pressiani, T., Destro, A., Roncalli, M., Crino, L., Franklin, W. A., Santoro, A., & Varella-Garcia, M.
- Affiliations
- IRCCS Humanitas Research Hospital (IT)
- University of Colorado Cancer Center (US)
- Ospedale Bellaria (IT)
- Policlinico San Matteo Fondazione (IT)
- University of Campania "Luigi Vanvitelli" (IT)
- Corresponding author
- Cappuzzo, F.
- ORCID
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 19
- Issue
- 4
- Pages
- 717-723
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2158475201
- Cited by
- 267
- References
- 39
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 6 · 2016: 8 · 2015: 12 · 2014: 18 · 2013: 20 · 2012: 24
- FWCI
- 18.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Università degli Studi di Napoli Federico II
- Cancer Center, University of Colorado
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- EGFR copy number, cetuximab, colorectal cancer, chemorefractory cancer, predictive biomarkers, treatment response prediction, time to progression, EGFR amplification
- MeSH terms
- Cetuximab, Adult, Aged, Antibodies, Monoclonal, Antineoplastic Agents, Antineoplastic Combined Chemotherapy Protocols, Female, Humans, Immunohistochemistry, Italy, Male, Middle Aged, Predictive Value of Tests, Retrospective Studies, ROC Curve, Sensitivity and Specificity, Biomarkers, Tumor, Colorectal Neoplasms, Confidence Intervals, Survival Analysis, Treatment Outcome, In Situ Hybridization, Fluorescence, Disease-Free Survival, Patient Selection, Drug Resistance, Neoplasm, Antibodies, Monoclonal, Humanized, ErbB Receptors
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