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Epiregulin gene expression as a biomarker of benefit from cetuximab in the treatment of advanced colorectal cancer.
- Source :
-
British journal of cancer [Br J Cancer] 2014 Feb 04; Vol. 110 (3), pp. 648-55. Date of Electronic Publication: 2013 Dec 12. - Publication Year :
- 2014
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Adult
Aged
Aged, 80 and over
Biomarkers, Tumor genetics
Cetuximab
Clinical Trials, Phase III as Topic
Colorectal Neoplasms genetics
Colorectal Neoplasms pathology
Disease-Free Survival
Epidermal Growth Factor genetics
Epiregulin
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Middle Aged
Mutation
Neoplasm Staging
Antibodies, Monoclonal, Humanized administration & dosage
Colorectal Neoplasms drug therapy
Epidermal Growth Factor biosynthesis
ras Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1532-1827
- Volume :
- 110
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- British journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 24335920
- Full Text :
- https://doi.org/10.1038/bjc.2013.753