Merck KGaA has been granted approval by the European Commission for Erbitux (cetuximab), to update its license for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type mCRC (metastatic colorectal cancer) in combination with chemotherapy, and as a single agent in patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to irinotecan.

"This broad approval of Erbitux in metastatic colorectal cancer is welcomed by the oncology community as it provides us with another treatment option for our patients in the 1st-line setting," commented Professor Eric Van Cutsem, Professor of Medicine and Digestive Oncology at the University Hospital Gasthuisberg in Leuven, Belgium. "We are excited by the data supporting this approval as it demonstrates the increased efficacy of Erbitux in patients who have KRAS wild-type tumors. The broadened approval of Erbitux is also a big step towards offering tailored therapies to patients with metastatic colorectal cancer."

The approval was granted following review of data from randomized, controlled phase III (CRYSTAL) and phase II (OPUS) trials that demonstrated the superior efficacy of Erbitux in combination with standard chemotherapy in the 1st-line treatment of patients with mCRC compared to chemotherapy alone. Further analyses of these trials, investigating the efficacy of Erbitux in patients with KRAS wild-type tumors, was also submitted to the authorities and recently presented at major scientific conferences - American Society of Clinical Oncology (ASCO) and World Congress on Gastro-Intestinal Cancers (WCGIC). These analyses found that patients with KRAS wild-type tumours experienced substantially increased efficacy with Erbitux and had statistically significant higher response rates (CRYSTAL: 59% vs 43%; OPUS: 61% vs 37%) and decreased risk of progression (CRYSTAL: by 32%; OPUS by 43%) than patients receiving chemotherapy alone.

"Erbitux is a key new treatment option for two-thirds of all metastatic colorectal cancer patients because the KRAS status of their tumours is predictive for the efficacy of Erbitux," said Wolfgang Wein, executive vice president, oncology, Merck Serono. "These findings are an important step forward in the development of tailored therapies."

Up to 65% of patients with mCRC have normal or non-mutated KRAS tumors, also scientifically known as wild-type. KRAS is a gene that codes for a protein involved in the EGFR pathway. In KRAS wild-type tumours, the KRAS protein is tightly regulated and only activated in response to certain stimuli such as EGFR signalling. In patients with normal KRAS status, Erbitux blocks a signalling pathway, preventing growth of a tumour. The KRAS mutation overrules this effect of Erbitux, thus allowing the tumour to continue to grow, proliferate and spread.

Erbitux has been licensed for the treatment of mCRC since June 2004 and locally advanced squamous cell carcinoma of the head and neck (SCCHN) since April 2006. So far, more than 120,000 patients have been treated with commercially available Erbitux worldwide. A submission to the European authorities to broaden the use of Erbitux in SCCHN to include 1st-line treatment of patients with recurrent and/or metastatic SCCHN was made in June 2008 by Merck Serono.

Erbitux is a first-in-class and highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it 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 tumour cells and the spread of tumours to new sites. It is also believed to inhibit the ability of tumour cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumours, which appears to lead to an overall suppression of tumour growth.

Merck licensed the right to market Erbitux outside the US and Canada from ImClone Systems Incorporated of New York in 1998. In Japan, ImClone Systems Incorporated, Bristol-Myers Squibb Company and Merck jointly develop and, upon approval, commercialize Erbitux. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas, such as the use of Erbitux in colorectal cancer, squamous cell carcinoma of the head and neck and non-small cell lung cancer. Merck has also acquired the rights for the cancer treatment UFT (tegafur-uracil) - an oral chemotherapy administered with folinic acid (FA) for the first-line treatment of metastatic colorectal cancer.