Two Phase III studies assessed the efficacy of Erbitux ( Cetuximab ) in metastatic colorectal cancer ( mCRC ).


In a Phase III study ( EPIC, European Prospective Investigation of Cancer ) Erbitux strongly favored the secondary endpoints of progression-free survival and response rate.
However, the study did not meet the primary endpoint of overall survival, possibly due to the fact that a considerable number of patients in the Irinotecan arm who had progressed on their therapy, subsequently received Cetuximab plus Irinotecan, a highly active treatment.
EPIC has compared Erbitux plus Irinotecan to Irinotecan in Irinotecan-naïve, epidermal growth factor receptor-expressing metastatic colorectal cancer patients who have failed prior Oxaliplatin-based chemotherapy.

Patients were randomized to one of two arms:

· arm 1 ( n = 648 ): patients received an initial dose of Cetuximab ( 400mg/m2 ) followed by a weekly dose of Cetuximab ( 250mg/m2 ), and Irinotecan 350mg/m2 every three weeks.

· arm 2 ( n = 650 ): patients received Irinotecan 350mg/m2 every three weeks.

The primary endpoint was overall survival. The secondary endpoints were progression-free survival, overall response rates, safety and quality of life.


Another Phase III study ( NCIC-CO.17 ) conducted by the National Cancer Institute of Canada Clinical Trials Group ( NCIC CTG ) in collaboration with the Australasian Gastro-Intestinal Trials Group ( AGITG ), evaluated Erbitux monotherapy versus best supportive care after failure of Irinotecan, Oxaliplatin, and fluoropyrimidines.

This study met its primary efficacy endpoint showing a statistically significant improvement in overall survival. These are the first data of an EGFR targeted antibody to demonstrate overall survival in the third-line treatment setting.

Patients were randomized to one or two treatment arms:

· arm 1 ( n = 287 ): patients received an initial dose of Cetuximab ( 400mg/m2 ) followed by a weekly dose of Cetuximab ( 250mg/m2 ). Patients also received best supportive care, defined as measures designed to provide palliation of symptoms and improve quality of life as much as possible.

· arm 2 ( n = 285 ): patients received best supportive care as in arm 1.

Erbitux is a first-in-class and highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor ( EGFR ).
Erbitux specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth. The most commonly reported side effect with Erbitux is an acne-like skin rash that seems to be correlated with a good response to therapy. In approximately five percent of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.

Metastatic colorectal cancer is a major health concern, with more than 370,000 people developing colorectal cancer in Europe per year, accounting for 13 percent of the total cancer burden and around 200,000 deaths. Approximately 25 percent of patients present with metastatic disease. Five-year survival rates for patients with metastatic colorectal cancer are as low as 5 percent.

Source: Merck KgaA, 2006


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