Epiregulin gene expression as a biomarker of benefit from cetuximab in the treatment of advanced colorectal cancer.

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.

• Authors: 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, S Khambata-Ford
• Journal: British journal of cancer (Br J Cancer) Vol. 110 Issue 3 Pg. 648-55 (Feb 04 2014) ISSN: 1532-1827 [Electronic] England
• PMID: 24335920 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Biomarkers, Tumor
• EREG protein, human
• Epiregulin
• Epidermal Growth Factor
• ras Proteins
• Cetuximab

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Biomarkers, Tumor (genetics)
• Cetuximab
• Clinical Trials, Phase III as Topic
• Colorectal Neoplasms (drug therapy, genetics, pathology)
• Disease-Free Survival
• Epidermal Growth Factor (biosynthesis, genetics)
• Epiregulin
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Male
• Middle Aged
• Mutation
• Neoplasm Staging
• ras Proteins (genetics)