TY - JOUR
T1 - Epiregulin gene expression as a biomarker of benefit from cetuximab in the treatment of advanced colorectal cancer
AU - Jonker, Derek
AU - Karapetis, Christos
AU - Harbison, Christopher
AU - O'Callaghan, Chris
AU - Tu, D
AU - Simes, R.
AU - Malone, Daniel
AU - Langer, Christiane
AU - Tebbutt, Niall
AU - Price, Timothy
AU - Shapiro, Jeremy
AU - Siu, L
AU - Wong, R
AU - Bjarnason, Georg
AU - Moore, Malcolm
AU - Zalcberg, John
AU - Khambata-Ford, Shirin
PY - 2014/1/1
Y1 - 2014/1/1
N2 - 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.
AB - 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.
KW - amphiregulin
KW - biomarker
KW - cetuximab
KW - colorectal
KW - EGFR
KW - epiregulin
KW - EREG
KW - K-ras
UR - http://www.scopus.com/inward/record.url?scp=84893721813&partnerID=8YFLogxK
U2 - 10.1038/bjc.2013.753
DO - 10.1038/bjc.2013.753
M3 - Article
SN - 0007-0920
VL - 110
SP - 648
EP - 655
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 3
ER -
