Journal
BRITISH JOURNAL OF CANCER
Volume 110, Issue 3, Pages 648-655Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2013.753
Keywords
epiregulin; EREG; colorectal; cetuximab; biomarker; EGFR; K-ras; amphiregulin
Categories
Funding
- Canadian Cancer Society through the NCIC Clinical Trials Group, ImClone Systems and Bristol-Myers Squibb
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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.
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