Merck Applies To Extend Use Of Erbitux For 1st-Line Head And Neck Cancer In Europe

Main Category: Cancer / Oncology
Also Included In: Ear, Nose and Throat;  Neurology / Neuroscience;  Regulatory Affairs / Drug Approvals
Article Date: 20 Jun 2008 - 1:00 PDT

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Merck KGaA announced that it has submitted an application to the European Medicines Agency (EMEA) to broaden the use of the targeted therapy Erbitux® (cetuximab) to include 1st-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). The submitted label would extend the use of Erbitux for treatment of patients with recurrent and/or metastatic squamous cell cancer of the head and neck in combination with platinum-based chemotherapy.

The submission is supported by data from the EXTREME study1 - ErbituX in 1st-line Treatment of REcurrent or MEtastatic head and neck cancer - investigating the efficacy of Erbitux in combination with platinum-based chemotherapy in the 1st-line setting in patients with recurrent and/or metastatic SCCHN. The study showed that when added to current standard platinum-based chemotherapy, Erbitux significantly increased the overall survival time for patients.

"Erbitux represents a real breakthrough for the 1st-line treatment of head and neck cancer as it is the first treatment in more than 30 years to show a significant survival benefit," said Dr. Wolfgang Wein, Executive Vice President, Oncology, Merck Serono. "If approved by the European Commission, this broader use of Erbitux would provide a new important treatment standard for patients with recurrent and/or metastatic head and neck cancer, an area where there is great clinical need."

The Phase III randomized EXTREME study involved 442 patients with previously untreated recurrent and/or metastatic SCCHN who were treated with either Erbitux plus platinum-based chemotherapy (cisplatin or carboplatin plus infusional 5-fluorouracil [5-FU]) or platinum-based chemotherapy alone. The study met the primary endpoint of significantly increasing overall survival - an improvement of 2.7 months (HR=0.797) was seen for patients treated with Erbitux plus platinum-based chemotherapy compared to chemotherapy alone. The median overall survival for patients in the Erbitux plus platinum-based chemotherapy arm was 10.1 months; and 7.4 months for patients treated with platinum-based chemotherapy alone.1 This is among the longest ever reported survival times in a Phase III trial for this patient population. Findings from the EXTREME study were presented at the American Society of Clinical Oncology congress in June 2007 and at the European Congress of Clinical Oncology (ECCO) in September 2007.1

The toxicity profile of Erbitux in combination with platinum-based chemotherapy was manageable and consistent with the current safety information.

The application for the 1st-line indication will be reviewed by the Committee for Medicinal Products for Human Use (CHMP). If approved by the European Commission, patients within Europe may then start benefiting from Erbitux as a 1st-line treatment for recurrent and/or metastatic SCCHN.

Erbitux has been licensed in the European Union for use in combination with radiotherapy for locally advanced SCCHN since April 3, 2006. In addition, Erbitux was first approved for the treatment of metastatic colorectal cancer (mCRC) after irinotecan failure in Switzerland in December 2003 and in the European Union in June 2004. Merck was also recently granted a positive opinion by the CHMP to broaden the use of Erbitux for all lines of treatment for patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type mCRC in combination with chemotherapy.

Head and neck cancer

In Europe alone, it is estimated that there are around 140,000 cases of head and neck cancer, and more than 65,000 deaths due to the disease each year.2 About 40% of patients suffering from head and neck cancer are in recurrent/metastatic state. Head and neck cancer is the sixth most frequently occurring cancer worldwide.3 Head and neck cancer includes cancers of the tongue, mouth, salivary glands, pharynx, larynx, sinus, and other sites located in the head and neck area. About 90% of head and neck cancers are of the squamous cell variety4 and nearly all express EGFR, which is critical for tumor growth.5 Although there have been significant improvements in chemotherapy and surgical techniques, the disease is particularly challenging to treat since most patients present with advanced disease, have secondary tumors and suffer from other co-morbidities.6

References

1. Vermorken JB, et al. J Clin Oncol 2007;25(18S). Abstract 6091.
2. GLOBOCAN (http://www-dep.iarc.fr, accessed June 2008).
3. http://www-dep.iarc.fr. April 2002.
4. Hunter KD, et al. Nat Rev Cancer. 2005 Feb; 5 (2): 127-35.
5. Bourhis J and Pinto H. Redefining 'State of the Art' in Head and Neck Cancer. Oral presentation, 6th International Conference on Head and Neck Cancer 7-11 August 2004.
6. Forastiere A, et al. N Engl J Med 2001:345(26), 1890-1900.

About ERBITUX

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 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 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 72 countries. It has been approved for the treatment of colorectal cancer in 71 countries so far: Argentina, Australia, Belarus, Canada, Chile, China, Colombia, Costa Rica, Croatia, Dominican Republic, Ecuador, El Salvador, the European Union, Guatemala, Honduras, Hong Kong, Iceland, India, Indonesia, Israel, Kazakhstan, Lebanon, Liechtenstein, Malaysia, Mexico, New Zealand, Nicaragua, Norway, Oman, Panama, Peru, the Philippines, Qatar, Russia, Serbia, Singapore, South Africa, South Korea, Switzerland, Taiwan, Thailand, Ukraine, Uruguay, the US, and Venezuela for use in combination with irinotecan in patients with EGFR-expressing mCRC who have failed prior irinotecan therapy. Erbitux is also approved for single-agent use in: Argentina, Australia, Canada, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Hong Kong, Lebanon, Mexico, New Zealand, Nicaragua, Panama, Peru, the Philippines, Russia, Singapore, Thailand, the US, and Venezuela.

In addition, Erbitux in combination with radiotherapy has been approved for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN) in 65 countries: Argentina, Australia, Belarus, Brazil, Chile, Colombia, Costa Rica, Croatia, El Salvador, the European Union, Guatemala, Hong Kong, Iceland, India, Indonesia, Israel, Kazakhstan, Lebanon, Liechtenstein, Malaysia, Mexico, New Zealand, Nicaragua, Norway, Oman, Panama, Peru, the Philippines, Qatar, Russia, Serbia, Singapore, South Africa, Switzerland, Taiwan, Ukraine, Uruguay, the US, and Venezuela. In Argentina, Chile, Costa Rica, El Salvador, Guatemala, Hong Kong, Israel, Lebanon, Mexico, Nicaragua, Peru, the Philippines, Russia, and the US, Erbitux is also approved as monotherapy in patients with recurrent and/or metastatic SCCHN who failed prior chemotherapy.

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.

Merck is also investigating among other cancer treatments the use of Stimuvax® (formerly referred to as 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., Bellevue, Washington, USA.

About Merck Serono

Merck Serono is the division for innovative prescription pharmaceuticals of Merck, a global pharmaceutical and chemical group. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets innovative small molecules and biopharmaceuticals to help patients with unmet medical needs. Its North American business operates in the United States and Canada as EMD Serono.

Merck Serono has leading brands serving patients with cancer (Erbitux®), multiple sclerosis (Rebif®), infertility (Gonal-f®), endocrine and cardiometabolic disorders (Glucophage®, Concor®, Saizen®, Serostim®), as well as psoriasis (Raptiva®).

With an annual R&D investment of around € 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 autoimmune and inflammatory diseases.

For more information, please visit http://www.merckserono.netor http://www.merck.de

About Merck

Merck is a global pharmaceutical and chemical company with total revenues of € 7.1 billion in 2007, a history that began in 1668, and a future shaped by 31,681 employees in 60 countries. 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%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.

http://www.merck.de