Merck KGaA: Erbitux – First treatment in 30 Years to Prolong Survival in 1st-Line Recurrent and/or Metastatic Head and Neck Cancer

Abstract number 6870: Predictors of efficacy in the EXTREME study: Cetuximab plus platinum-based therapy 1st-line in patients with recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN)
Abstract number 693: Cetuximab plus platinum-based therapy 1st-line in patients with recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): A quality of life (QoL) analysis of the EXTREME trial

Location: 33rd European Society for Medical Oncology (ESMO) Congress, Stockholm, Sweden


• Addition of Erbitux to standard 1st-line chemotherapy in head and neck cancer showed significantly improved median overall survival, progression-free survival and increased response rate, while maintaining quality of life. This is the first major advance since the introduction of platinum-based chemotherapy in 1977.

STOCKHOLM/DARMSTADT, September 14, 2008 – Data presented today at the 33rd European Society for Medical Oncology (ESMO) Congress in Stockholm demonstrate that the addition of Erbitux® (cetuximab) to platinum-based chemotherapy increases overall survival (OS) compared to chemotherapy alone in the 1st-line treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN).1  Furthermore the data showed the significant benefits of Erbitux were achieved without any detrimental impact on quality of life (QoL).2

“These data are incredibly exciting as they represent the first advance in the 1st-line treatment of head and neck cancer in this setting for three decades. For the first time since the introduction of platinum-based chemotherapy we are able to increase the overall survival time for recurrent and/or metastatic head and neck cancer patients,” said Professor Jan B. Vermorken, lead investigator of the EXTREMEa trial and head of the Department of Medical Oncology, Antwerp University Hospital, Belgium.

The EXTREME study was a multicenter, randomized, controlled, Phase III trial involving 442 patients, designed to assess the efficacy of Erbitux combined with cisplatin or carboplatin plus 5-fluorouracil (5-FU) versus chemotherapy alone in the 1st-line treatment of patients with recurrent and/or metastatic SCCHN.1 Patients treated with Erbitux plus chemotherapy experienced the following improvements, compared to chemotherapy alone:1
• Increased median overall survival of nearly 3 months (10.1 vs. 7.4 months; p=0.04), equating to a 20% risk reduction of death (HR: 0.80) during the study period
• A 70% increase in median progression-free survival (5.6 vs. 3.3 months; p<0.001)
• An 80% relative increase in response rate (36% vs. 20%; p<0.001)

The EXTREME trial also assessed the impact of treatment on quality of life (QoL) using two assessment questionnaires (QLQ-C30 and QLQ-H&N35) developed by the European Organization for Research and Treatment of Cancer (EORTC).2 QLQ-C30 is designed to assess QoL in cancer patients in general, whilst QLQ-H&N35 focuses specifically on head and neck cancer.3 Analysis of the completed questionnaires showed that the addition of Erbitux to chemotherapy delivered in most cases  significant and clinically relevant benefits without impacting tolerability. Moreover, the QLQ-H&N35 results showed that patients receiving Erbitux saw significant improvement in areas such as pain and swallowing.2

“It is very encouraging to see that the positive impact Erbitux has on survival in patients with SCCHN is not accompanied by any additional, detrimental effects on quality of life. Indeed, the life quality benefits that our patients experience due to the tumor shrinkage induced by Erbitux therapy can make a real difference,” said Professor Vermorken.

The EXTREME study forms the basis of an application to the European Medicines Agency (EMEA), submitted in June of this year, to broaden the use of Erbitux from its current indication in locally advanced SCCHN to include the 1st-line treatment of patients with recurrent and/or metastatic disease.

Also presented at ESMO was a retrospective analysis of the EXTREME study which investigated the influence of epidermal growth factor receptor (EGFR) expression and gene copy number status on overall survival. No association was found between either EGFR expression or gene copy number status and overall survival in Erbitux-treated patients.1 Currently, there is no evidence to suggest that these predictive biomarkers play a clinically relevant role in the treatment of recurrent and/or metastatic SCCHN.4

Furthermore, the KRAS biomarker, found to be an important predictor of treatment efficacy in metastatic colorectal cancer, is not of importance in SCCHN, where nearly 95% of tumors are KRAS wild-type.5

Head and neck cancer
In Europe, 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.6 About 40% of patients with head and neck cancer have recurrent and/or metastatic SCCHN. Head and neck cancer is the sixth most frequently occurring cancer worldwide6,7 and 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 variety8 and nearly all express EGFR, which is critical for tumor growth.9 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 and often have secondary tumors, in addition to suffering from other co-morbidities.10 At least 75% of all head and neck cancers are attributed to its two major risk factors, smoking tobacco and alcohol consumption.11

a EXTREME: ErbituX in 1st-line Treatment of REcurrent or MEtastatic head and neck cancer


References
1. Vermorken JB, et al, ESMO 2008; Abstract No: 6870.
2. Rivera Herrero F, et al. ESMO 2008; Abstract No: 693.
3. http://groups.eortc.be/qol/index.htm.
4. Argiris A, et al. Lancet 2008;371:1695-1709.
5. Weber A, et al. Oncogene 2003;22:4757-59.
6. GLOBOCAN 2002 (www-dep.iarc.fr, accessed August 2008).
7. Vermorken JB, et al. J Clin Oncol 2007;25(18S).
8. Hunter KD, et al. Nat Rev Cancer 2005; (2):127-35.
9. 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.
10. Forastiere A, et al. N Engl J Med 2001;345(26):1890-900.
11. Hashibe M, et al. J Natl Inst 2007;99:777-89.

For more information on Erbitux in colorectal, head & neck and non-small cell lung cancer, please visit: www.globalcancernews.com.

 


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 75 countries. It has been approved for the treatment of colorectal cancer in 74 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, Japan, Kazakhstan, Kuwait, Lebanon, Liechtenstein, Malaysia, Mexico, Moldavia, 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, Japan, Lebanon, Mexico, Moldavia, New Zealand, Nicaragua, Panama, Peru, the Philippines, Russia, Singapore, Thailand, the US, and Venezuela. In the European Union, the license was updated in July 2008 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.

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 68 countries: Argentina, Australia, Belarus, Brazil, Chile, Colombia, Costa Rica, Croatia, El Salvador, the European Union, Guatemala, Hong Kong, Iceland, India, Indonesia, Israel, Kazakhstan, Kuwait, Lebanon, Liechtenstein, Malaysia, Mexico, Moldavia, New Zealand, Nicaragua, Norway, Oman, Panama, Peru, the Philippines, Qatar, Russia, Serbia, Singapore, South Africa, South Korea, Switzerland, Taiwan, Ukraine, Uruguay, the US, and Venezuela. In Argentina, Chile, Costa Rica, El Salvador, Guatemala, Hong Kong, Israel, Lebanon, Mexico, Moldavia, 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 www.merckserono.net or www.merck.de


About Merck
All Merck Press Releases are distributed by e-mail at the same time they become available on the Merck Website. Please go to http://www.subscribe.merck.de to register online, change your selection or discontinue this service.

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 31,946 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.
 

Contact
Dr. Raphaela Farrenkopf
Phone +49 6151-72 2274

Posted: September 2008

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