KRAS Gene Mutation Linked with Poor Response to Erbitux® in Colorectal Cancer
Among patients with metastatic colorectal cancer, those whose cancers contain a mutation in the KRAS gene appear to be less likely than other patients to respond to treatment with Erbitux® (cetuximab) and chemotherapy. These results were published in the British Journal of Cancer.
Colorectal cancer remains the second leading cause of cancer-related death in the United States. Metastatic colorectal cancer refers to cancer that has spread from the colon to distant sites in the body.
Erbitux is a type of targeted therapy called a monoclonal antibody. It works by binding to a protein receptor located on many cancer cells called the epidermal growth factor receptor (EGFR). EGFR is involved in cellular growth and replication, and by targeting EGFR, the spread of cancer can be reduced or delayed.
Response to Erbitux and other drugs may be influenced by mutations in specific genes. If gene mutations are found to predict response to treatment, information about a patient’s genetic status may help doctors select the best treatment for that patient. KRAS is a gene that may influence response to Erbitux.
To evaluate the relationship between KRAS mutations and response to treatment with a combination of chemotherapy and Erbitux, researchers conducted a study among 59 patients with metastatic colorectal cancer who had failed to respond to at least one previous chemotherapy regimen. All study participants were treated with a combination of Erbitux and chemotherapy.
- A KRAS mutation in cancer tissue was detected in 22 out of 59 patients. None of the patients with a KRAS mutation experienced a reduction in cancer following treatment with Erbitux and chemotherapy.
- Of the 37 patients without a KRAS mutation, 12 experienced a partial or complete disappearance of detectable cancer following treatment with Erbitux and chemotherapy.
- Cancer progressed more quickly in patients with a KRAS mutation than in patients without a KRASmutation.
The researchers conclude that the presence of a KRAS mutation in cancer tissue reduces the likelihood that patients with metastatic colorectal cancer will respond to treatment with Erbitux and chemotherapy. The researchers note that larger studies are needed to confirm this finding.
Di Fiore F, Blanchard F, Charbonnier F et al. Clinical relevance of KRAS mutation detection in metastatic colorectal cancer treated by cetuximab plus chemotherapy. *British Journal of Cancer.*2007;96:1166-1169.