Merck Serono, a division of Merck KGaA, Darmstadt, Germany, highlighted a further analysis of the large randomized phase II OPUSa study demonstrating an association between early tumour shrinkage and long-term median Overall Survival (OS) of more than 2 years for patients with KRAS wild-type metastatic Colo-Rectal Cancer (mCRC) treated with Erbitux (cetuximab) plus Folfox standard chemotherapy. This correlation was not seen in the chemotherapy-alone arm of the study. The study will be presented at the annual Gastrointestinal (GI) Cancers Symposium of the American Society of Clinical Oncology (ASCO).

This latest analysis shows that the majority of patients (69%) with KRAS wild-type mCRC demonstrated tumour shrinkage of 20% or more in the first 8 weeks of 1st line treatment with Erbitux and Folfox. These patients experienced a long-term median OS of 26.2 months. Patients treated with Folfox chemotherapy alone whose tumours shrank by 20% or more in the same period (46%) experienced median OS of only 21.8 months.

These results support recent findings from the phase III Crystal b trial, which found that early tumour shrinkage achieved with Erbitux in combination with Folfiri standard chemotherapy led to a long-term median OS of 2.4 years (28.3 months).

“The Opus and Crystal studies show, for the first time in colorectal cancer, that there is a correlation between early tumour shrinkage during the first weeks of treatment and extended survival. This effect seems to be unique to treatment with chemotherapy and Erbitux since a similar association was not observed with chemotherapy alone in this analysis, nor has it been proved for any other colorectal cancer treatment,” said Professor Carsten Bokemeyer, lead investigator of the OPUS trial, Head of the Department for Oncology, Haematology and Bone Marrow Transplantation in the Centre for Internal Medicine at the University Medical Centre in Hamburg, Germany. “The result is both scientifically of extreme interest and immediately medically relevant for improving patient care through the personalized medicine approach with Erbitux.”

Further Erbitux data to emerge from ASCO GI came from the randomized Phase II CORE.1.2.002 study that included 152 patients. The results showed that administration of Erbitux every second week in combination with Folfox resulted in sustained efficacy and safety in the treatment of mCRC patients with KRAS wild-type tumours, which were equivalent to the results demonstrated with the weekly administration. Response rates of 51% and 63% were seen in the weekly administration arm and in the arm where Erbitux was given every second week, respectively. There was no significant difference between the two arms.

“Results from both the Core.1.2.002 and Opus studies confirm the high activity of Erbitux with the standard Folfox oxaliplatin-based chemotherapy regimen,” said Dr. Wolfgang Wein, executive vice president, Oncology, Merck Serono. “The latest long-term survival data from the Opus and Crystal studies, using the Folfox and Folfiri standard chemotherapies respectively, show that the strong tumour shrinkage of Erbitux directly translates into extended survival for patients.”

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.

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 5% of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.

Erbitux has already obtained market authorization in 86 countries. It has been approved for the treatment of colorectal cancer in 86 countries and for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 82 countries: December 2003 (Switzerland), February 2004 (USA), June 2004 (EU) and followed by other countries: for use in combination with irinotecan in patients with EGFR-expressing mCRC (metastatic colorectal cancer) who have failed prior irinotecan therapy. In addition, Erbitux is also approved for single-agent use in further countries. March 2006 (EU) and followed by other countries: for use in combination with radiotherapy for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). In further countries, Erbitux is also approved as monotherapy in patients with recurrent and/or metastatic SCCHN who failed prior chemotherapy. July 2008 (EU): license was updated for the treatment of patients with epidermal growth factor receptor (EGFR) expressing, KRAS wild-type mCRC 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. July 2008 (Japan): for use in combination with irinotecan in patients with EGFR-expressing mCRC who have failed prior irinotecan therapy. In November 2008 (EU): license was updated for the use in combination with platinum-based chemotherapy in patients with recurrent and/or metastatic SCCHN. March 2010 (Japan): label extended to use in combination with chemotherapy in the 1st-line treatment for patients with epidermal growth factor receptor (EGFR)-expressing, curatively unresectable (inoperable), advanced or recurrent colorectal cancer (mCRC) carrying the KRAS wild-type gene.

Merck licensed the right to market Erbitux outside the US and Canada from ImClone LLC, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. In Japan, ImClone, Bristol-Myers Squibb Company and Merck jointly develop and 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.

Merck is also investigating among other potential cancer treatments the use of Stimuvax (BLP25 Liposome Vaccine) in the treatment of non-small cell lung cancer. The vaccine was granted fast-track status in September 2004 by the FDA. Merck obtained the exclusive worldwide licensing rights from Oncothyreon Inc., Seattle, Washington, USA.

In addition, Merck is developing cilengitide, which is the first in a new class of investigational anti-cancer therapies called integrin inhibitors to reach Phase III development; it is currently being investigated for the treatment of glioblastoma, SCCHN and NSCLC. Integrin inhibitors are thought to work by targeting the tumour and its vasculature.

Merck Serono is the biopharmaceutical division of Merck KGaA, Darmstadt, Germany, a global pharmaceutical and chemical company. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets prescription medicines of both chemical and biological origin in specialist indications. In the United States and Canada, EMD Serono operates as a separately incorporated affiliate of Merck Serono.

Merck Serono has leading brands serving patients with cancer (Erbitux, cetuximab), multiple sclerosis (Rebif, interferon beta-1a), infertility (Gonal-f, follitropin alfa), endocrine and metabolic disorders (Saizen and Serostim, somatropin), (Kuvan, sapropterin dihydrochloride) as well as cardiometabolic diseases (Glucophage, metformin), (Concor, bisoprolol), (Euthyrox, levothyroxine). Not all products are available in all markets.

With an annual R&D expenditure of over € 1bn, Merck Serono is committed to growing its business in specialist-focused therapeutic areas including neurodegenerative diseases, oncology, fertility and endocrinology, as well as new areas potentially arising out of research and development in rheumatology.

Merck is a global pharmaceutical and chemical company and its success is characterized by innovations from entrepreneurial employees. Merck's operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%.