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Title: Epiregulin gene expression as a biomarker of benefit from cetuximab in the treatment of advanced colorectal cancer.
Austin Authors: Jonker, D J;Karapetis, C S;Harbison, C;O'Callaghan, Christopher J ;Tu, D;Simes, R J;Malone, D P;Langer, C;Tebbutt, Niall C ;Price, Timothy J;Shapiro, J;Siu, L L;Wong, R P W;Bjarnason, G;Moore, M J;Zalcberg, John R;Khambata-Ford, S
Affiliation: The Ottawa Hospital Research Institute, University of Ottawa, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada
Flinders Medical Centre and Flinders University, Flinders Drive, Bedford Park, Adelaide, SA 5042, Australia
Peter MacCallum Cancer Centre, Australasian Gastrointestinal Trials Group, University of Melbourne, 1 Street Andrews Place, East Melbourne, VIC 3002, Australia
Cabrini Hospital and Monash University, Isabella Street, Malvern, VIC 3144, Australia
The Queen Elizabeth Hospital and University of Adelaide, 28 Woodville Road, Woodville South SA 5011, Australia
Austin Health and University of Melbourne, 145 Studley Road, Heidelberg, VIC 3084, Australia
Princess Margaret Hospital and University of Toronto, 610 University Avenue, Suite 5-718, Toronto, ON M5G 2M9, Canada
Research and Development, Bristol-Myers Squibb, 100 Nassau Park Boulevard, Princeton, NJ 08540, USA
National Health and Medical Research Council Clinical Trials Centre, University of Sydney, ABN 15 211 513 464, Camperdown, NSW 1450, Australia
Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada
Cancercare Manitoba, St Boniface General Hospital, 409 Tache Avenue, Rm L1-102, Winnipeg, MB R2H 2A6, Canada
NCIC - Clinical Trials Group, Queens University, Cancer Research Institute, 10 Stuart Street, Kingston, ON K7P 3E3, Canada
Genetech Inc., 1 Dna Way, South San Francisco, CA 94080, USA
Issue Date: 12-Dec-2013
Publication information: British Journal of Cancer 2013; 110(3): 648-55
Abstract: 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.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.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.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.
Gov't Doc #: 24335920
DOI: 10.1038/bjc.2013.753
Type: Journal Article
Subjects: Adult
Aged, 80 and over
Antibodies, Monoclonal, Humanized.administration & dosage
Clinical Trials, Phase III as Topic
Colorectal Neoplasms.drug therapy.genetics.pathology
Disease-Free Survival
Epidermal Growth Factor.biosynthesis.genetics
Gene Expression Regulation, Neoplastic
Middle Aged
Neoplasm Staging
Tumor Markers, Biological.genetics
ras Proteins.genetics
Appears in Collections:Journal articles

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