Summary

Antibody treatments for cancer target the molecular pathways involved in the disease and they have shown some survival benefit in colorectal and other cancers. However, not all patients respond to these therapies. A new study, looking back at tissue samples, now reveals that mutations in a particular gene prevent a patient from benefiting from treatment with the antibody cetuximab.

Introduction

Cetuximab is an antibody drug that targets a molecule called EGFR (epidermal growth factor receptor) that is known to be involved in cancer. Blocking EGFR, put simply, stops cancer in its tracks. The drug is approved for treatment of advanced colorectal cancer, but it is known that not all patients respond to it. Looking back at tissue samples of those who did and did not respond is a good way of working out the factors involved in response to cetuximab.

What was done

Tumor tissue samples from 394 patients in a clinical trial of cetuximab have been examined by researchers in the United States and Australia. Some of the patients received cetuximab and some received standard best care. DNA analysis was performed to see if patients had mutations in the gene for K-ras and whether this affected their response to treatment.

What was found

Mutations in K-ras were found in 42.3 percent of samples. Patients who did not have a mutation had a significant increase in survival - around five months - when treated with cetuximab compared to those who did have a mutation. This group gained no benefit from the new drug.

What this study means

Mutations in K-ras appear to be an important biomarker for treatment with cetuximab. The European Medicines Agency has already taken this on board and it is likely that the United States Food and Drug Administration will also do so. Therefore, those patients who can benefit should be able to receive this drug and those who cannot will, at least, not be given false hope.