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Type: Journal article
Title: Epiregulin gene expression as a biomarker of benefit from cetuximab in the treatment of advanced colorectal cancer
Author: Jonker, D.
Karapetis, C.
Harbison, C.
O'Callaghan, C.
Tu, D.
Simes, R.
Malone, D.
Langer, C.
Tebbutt, N.
Price, T.
Shapiro, J.
Siu, L.
Wong, R.
Bjarnason, G.
Moore, M.
Zalcberg, J.
Khambata-Ford, S.
Citation: British Journal of Cancer, 2014; 110(3):648-655
Publisher: Cancer Research UK
Issue Date: 2014
ISSN: 0007-0920
Statement of
D J Jonker, C S Karapetis, C Harbison, C J O'Callaghan, D Tu, R J Simes, D P Malone, C Langer, N Tebbutt, T J Price, J Shapiro, L L Siu, R P W Wong, G Bjarnason, M J Moore, J R Zalcberg and S Khambata-Ford
Abstract: BACKGROUND: Anti-EGFR antibody, cetuximab, improves overall survival (OS) in K-ras wild-type chemotherapy-refractory colorectal cancer. Epidermal growth factor receptor ligand epiregulin (EREG) gene expression may further predict cetuximab benefit. METHODS: Tumour samples from a phase III clinical trial of cetuximab plus best supportive care (BSC) vs BSC alone (CO.17) were analysed for EREG mRNA gene expression. Predictive effects of high vs low EREG on OS and progression-free survival (PFS) were examined for treatment-biomarker interaction. RESULTS: Both EREG and K-ras status were ascertained in 385 (193 cetuximab, 192 BSC) tumour samples. Within the high EREG and K-ras wild-type status ('co-biomarker')-positive group (n=139, 36%), median PFS was 5.4 vs 1.9 months (hazard ratio (HR) 0.31; P<0.0001), and median OS was 9.8 vs 5.1 months (HR 0.43; P<0.001) for cetuximab vs BSC, respectively. In the rest (n=246, 64%), PFS (HR 0.82; P=0.12) and OS (HR 0.90; P=0.45) were not significantly different. Test for treatment interaction showed a larger cetuximab effect on OS (HR 0.52; P=0.007) and PFS (HR 0.49; P=0.001) in the co-biomarker-positive group. CONCLUSION: In pre-treated K-ras wild-type status colorectal cancer, patients with high EREG gene expression appear to benefit more from cetuximab therapy compared with low expression. Epiregulin as a selective biomarker requires further evaluation.
Keywords: epiregulin; EREG; colorectal; cetuximab; biomarker; EGFR; K-ras; amphiregulin
Description: Results were previously presented in part as a poster discussion session at the 2009 Annual Meeting of the American Society of Clinical Oncology (J Clin Oncol 2009; 27:15s (suppl; abstr 4016)). Published online 12 December 2013.
Rights: © 2014 Cancer Research UK. All rights reserved. From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit
RMID: 0030013881
DOI: 10.1038/bjc.2013.753
Appears in Collections:Medicine publications

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