Can epiregulin gene expression predict response to cetuximab?

This study evaluated epiregulin gene expression as a potential predictive marker of benefit from cetuximab therapy in the treatment of advanced colorectal cancer.

Colorectal cancer is cancer that affects the colon and the rectum, two components of the digestive system. Treatment depends on many things, including the stage of the cancer, the location of the tumor and individual characteristics of the patient.  Cetuximab (Erbitux) is a drug that inhibits the action of proteins called epidermal growth factor receptors found on the surface of some cancer cells. These growth factor receptors trigger the cancer cells to divide and grow. The K-ras protein is an important component in this signaling pathway, and the status of the K-ras gene is the only marker of cetuximab use; patients without K-ras gene mutations (i.e. wild type/normal K-ras) benefit most.

Epiregulin is a signal-triggering molecule that binds to epidermal growth factor receptors. This study evaluates epiregulin expression as a true marker of benefit from cetuximab therapy

This study involved 385 patients. 193 patients were randomly assigned to receive cetuximab in addition to best supportive care while 192 patients received best supportive care alone. These patients were categorized according to the status of the K-ras gene (wild type K-ras or mutant K-ras) and epiregulin expression (low or high epiregulin expression).

In patients with high expression of epiregulin, K-ras wild type patients treated with cetuximab had an average overall survival of 9.8 months compared to 5.1 months in those on best supportive care alone.

In patients with low expression of epiregulin, K-ras wild type patients treated with cetuximab did not show a significant improvement in overall survival (6.51 months) versus those on best supportive care alone (4.8 months). Similarly, cetuximab therapy did not significantly improve overall survival in patients with low epiregulin expression and K-ras mutant.

In patients with high expression of epiregulin, K-ras wild type patients treated with cetuximab had an average progression free survival (length of time during and after cancer treatment a patient lives without worsening of the disease) of 5.4 months compared to 1.9 months in those on best supportive care alone. Cetuximab therapy was not associated with better progression free survival in patients with K-ras wild type and low epiregulin expression.

In patients with high expression of epiregulin, those treated with cetuximab had a 16.7% treatment response rate, while those on best supportive care alone had 0% treatment response rate. This response was not reflected in patients with low epiregulin expression.

This study concluded that tumor epiregulin expression could be used as a predictive biomarker of overall survival and progression free survival for cetuximab therapy in patients with wild-type K-ras advanced colorectal tumors.

This study included a small number of patients. Therefore, epiregulin as a selective biomarker requires further evaluation in studies involving larger populations.