KRAS Affects Outcomes with Erbitux® in Colorectal Cancer

The KRAS mutation affects survival among patients with colorectal cancer who are treated with Erbitux (cetuximab). These results were recently published in the New England Journal of Medicine.

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. Recent studies have indicated that KRAS mutations affect responses to any agents targeting the EGFR pathway. Researchers continue to further refine these new findings and ultimately individualize therapy for these patients.

Researchers from several medical institutions recently conducted a clinical trial to evaluate the effects of KRAS mutation status on response and survival among patients with colorectal cancer treated with Erbitux. This study included 394 patients who had received treatment with either Erbitux or supportive care only (treatment to relieve symptoms but not treat the disease). Samples of tissue from the cancer were tested for KRAS mutations and outcomes were analyzed according to these mutations.

Among individuals who did not have mutations within their KRAS gene, overall survival was significantly improved if they had received treatment with Erbitux (9.5 months) compared to best supportive care (4.8 months). Progression-free survival was also improved among patients with no mutations in their KRAS gene if they received treatment with Erbitux versus supportive care only.®

Among patients with mutations in their KRAS gene, there was no difference in overall survival or progression-free survival between patients treated with Erbitux or supportive care, regardless of treatment group. Among patients treated with supportive care only, there were no differences in overall survival or progression-free survival.

The researchers concluded that colorectal cancer patients with KRAS mutations do not benefit from treatment with Erbitux, whereas those without KRAS mutations achieve significantly improved survival with Erbitux compared to supportive care. These results confirm prior studies evaluating this issue. All patients eligible for treatment with Erbitux should discuss KRAS testing with their healthcare providers. Trials are ongoing to further evaluate KRAS mutation status and the effects of other EGFR targeted therapies.

Reference: Karapetis C, Khambata-Ford S, Jonker D, et al. K-ras Mutations and Benefit from Cetuximab in Advanced Colorectal Cancer. New England Journal of Medicine. 2008; 359:1757-1765.

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