HER2 in high-risk rectal cancer patients treated in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab
Open accessAbstract
Background HER2 is an established therapeutic target in breast and gastric cancers. The role of HER2 in rectal cancer is unclear, as conflicting data on the prevalence of HER2 expression in this disease have been reported. We evaluated the prevalence of HER2 and its impact on the outcome of high-risk rectal cancer patients treated with neoadjuvant CAPOX and CRT±cetuximab in the EXPERT-C trial.Patients and methods Eligible patients with available tumour tissue for HER2 analysis were included. HER2 expression was determined by immunohistochemistry (IHC) in pre-treatment biopsies and/or surgical specimens (score 0-3+). Immunostaining was scored according to the consensus panel recommendations on HER2 scoring for gastric cancer. Tumours with equivocal IHC result (2+) were tested for HER2 amplification by D-ISH. Tumours with IHC 3+ or D-ISH ratio ≥2.0 were classified as HER2+. The impact of HER2 on primary and secondary end points of the study was analysed.Results Of 164 eligible study patients, 104 (63%) biopsy and 114 (69%) surgical specimens were available for analysis. Only 3 of 104 (2.9%) and 3 of 114 (2.6%) were HER2+, respectively. In 77 patients with paired specimens, concordance for HER2 status was found in 74 (96%). Overall, 141 patients were assessable for HER2 and 6 out of 141 (4.3%) had HER2 overexpression and/or amplification. The median follow-up was 58.6 months. HER2 was not associated with a difference in the outcome for any of the study end points, including in the subset of 90 KRAS/BRAF wild-type patients treated±cetuximab.Conclusions Based on the low prevalence of expression as recorded in the EXPERT-C trial, HER2 does not appear to represent a useful therapeutic target in high-risk rectal cancer. However, the role of HER2 as a potential predictive biomarker of resistance to anti-EGFR-based treatments and a therapeutic target in anti-EGFR refractory metastatic colorectal cancer (CRC) warrants further investigation.Trial registration ISRCTN Register: 99828560.
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A total of 2-7% of unselected colorectal cancers have ERBB2 mutations, and this number is higher in KRAS wild-type cases (13.6%) and in KRAS/NRAS/BRAF/PIK3CA quadruple wild-type cases (36%).
“A total of 2–7% of unselected CRCs were found to have ERBB2/mutations, and this number was much higher in KRAS wild-type cases (13.6%) and in KRAS/NRAS/BRAF/PIK3CA quadruple wild-type cases (36% )[13, 113, 114].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [114]
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References 21 · Cited by 33
- Authors
- Sclafani, F., Roy, A., Cunningham, D., Wotherspoon, A., Peckitt, C., Gonzalez de Castro, D., Tabernero, J., Glimelius, B., Cervantes, A., Eltahir, Z., Oates, J., & Chau, I.
- Affiliations
- Royal Marsden NHS Foundation Trust (GB)
- Universitat Autònoma de Barcelona (ES)
- Uppsala University Hospital (SE)
- Universitat de València (ES)
- Corresponding author
- Cunningham, D.
- ORCID
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 24
- Issue
- 12
- Pages
- 3123-3128
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2164317498
- Cited by
- 33
- References
- 21
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 1
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Annals of Oncology (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- Pelican Cancer Foundation
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Gastric Cancer Management and Outcomes
- Keywords
- HER2 expression, rectal cancer, high-risk rectal cancer, chemoradiotherapy, cetuximab, anti-EGFR therapy, predictive biomarkers, HER2 amplification, neoadjuvant therapy, metastatic colorectal cancer, treatment resistance, immunohistochemistry scoring, DNA in situ hybridization, therapeutic target, overall survival
- MeSH terms
- Cetuximab, Capecitabine, Oxaliplatin, Adenocarcinoma, Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Deoxycytidine, Female, Fluorouracil, Humans, Male, Middle Aged, Organoplatinum Compounds, Rectal Neoplasms, Retrospective Studies, Proportional Hazards Models, Single-Blind Method, Treatment Outcome, Chemotherapy, Adjuvant, Disease-Free Survival, Erb-b2 Receptor Tyrosine Kinases, Neoadjuvant Therapy, Chemoradiotherapy, Antibodies, Monoclonal, Humanized
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