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Clinical Trial
. 2007 Aug 1;25(22):3230-7.
doi: 10.1200/JCO.2006.10.5437.

Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab

Shirin Khambata-Ford  1 , Christopher R Garrett, Neal J Meropol, Mark Basik, Christopher T Harbison, Shujian Wu, Tai W Wong, Xin Huang, Chris H Takimoto, Andrew K Godwin, Benjamin R Tan, Smitha S Krishnamurthi, Howard A Burris 3rd, Elizabeth A Poplin, Manuel Hidalgo, Jose Baselga, Edwin A Clark, David J Mauro
Affiliations
Clinical Trial

Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab

Shirin Khambata-Ford et al. J Clin Oncol. .

Abstract

Purpose: The antiepidermal growth factor receptor (EGFR) antibody cetuximab shows activity in multiple epithelial tumor types; however, responses are seen in only a subset of patients. This study was conducted to identify markers that are associated with disease control in patients treated with cetuximab.

Patients and methods: One hundred ten patients with metastatic colorectal cancer were enrolled onto a cetuximab monotherapy trial. Transcriptional profiling was conducted on RNA from mandatory pretreatment metastatic biopsies to identify genes whose expression correlates with best clinical responses. EGFR and K-ras mutation analyses and EGFR gene copy number analyses were performed on DNA from pretreatment biopsies.

Results: Gene expression profiles showed that patients with tumors that express high levels of the EGFR ligands epiregulin and amphiregulin are more likely to have disease control with cetuximab (EREG, P = .000015; AREG, P = .000025). Additionally, patients whose tumors do not have K-ras mutations have a significantly higher disease control rate than patients with K-ras mutations (P = .0003). Furthermore, patients with tumors that have high expression of EREG or AREG also have significantly longer progression-free survival (PFS) than patients with low expression (EREG: P = .0002, hazard ratio [HR] = 0.47, and median PFS, 103.5 v 57 days, respectively; AREG: P < .0001, HR = 0.44, and median PFS, 115.5 v 57 days, respectively).

Conclusion: Patients with tumors that have high gene expression levels of epiregulin and amphiregulin and patients with wild-type K-ras are more likely to have disease control on cetuximab treatment. The identified markers could be developed further to select patients for cetuximab therapy.

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