Erbitux First Treatment In 30 Years To Significantly Prolong Survival In 1st-Line Recurrent And/Or Metastatic Head And Neck Cancer

Main Category: Cancer / Oncology
Also Included In: Clinical Trials / Drug Trials
Article Date: 12 Sep 2008 - 0:00 PDT

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Data published in the New England Journal of Medicine show that Erbitux® (cetuximab) significantly increases overall survival when added to standard chemotherapy in the 1st-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN).1 Results from the EXTREMEa trial also show that the addition of Erbitux to platinum-based chemotherapy significantly increases both median progression-free survival and tumor response rate, supporting the use of Erbitux in combination with chemotherapy as a new standard for 1st-line treatment of recurrent and/or metastatic SCCHN.1

"These findings are very exciting as they represent the first breakthrough in the treatment of head and neck cancer in this disease setting in 30 years," commented Professor Jan B. Vermorken, lead investigator of the EXTREME trial and head of the Department of Medical Oncology, Antwerp University Hospital, Belgium. "The inclusion of Erbitux as part of the standard 1st-line treatment regimen for SCCHN will give patients valuable time with prolonged symptomatic relief from the effects of this aggressive form of cancer that is so difficult to treat."

EXTREME was an open-label, multicenter, randomized, controlled Phase III trial that studied a total of 442 patients with previously untreated recurrent and/or metastatic SCCHN, who were randomized to receive Erbitux plus cisplatin or carboplatin and 5-fluorouracil (5-FU), or chemotherapy alone.1 The study found that the addition of Erbitux led to the following statistically significant outcomes: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))
- 80% relative increase in tumor response rate (36% vs. 20%; p<0.001)

The safety profile of the Erbitux plus chemotherapy combination was also studied during the trial, and it showed that the addition of Erbitux to platinum-based chemotherapy increased the toxicity only to a limited extent and proved to be feasible with manageable and predictable side effects, demonstrating that Erbitux can be added to platinum-based chemotherapy with confidence as a standard 1st-line treatment.1 Results from the EXTREME study have also shown that the addition of Erbitux to platinum-based chemotherapy delivers significant and clinically relevant benefits without impacting quality of life.2

"The first data highlighting the potential of Erbitux as a treatment for head and neck cancer, from Bonner et al, were published in the New England Journal of Medicine in 2006," said Dr Anton Hoos, Executive Vice President, Global Development, Merck Serono. "The data resulting from the EXTREME study which have now been published in the NEJM are the next piece of the puzzle. They demonstrate the important role Erbitux can play in this treatment area - including 1st-line recurrent and/or metastatic disease which is an area of high unmet clinical need."

Erbitux is already approved for use in locally advanced SCCHN in combination with radiotherapy and the results of the EXTREME trial have been used to support an EMEA application to broaden the use of Erbitux to include 1st-line treatment of recurrent and/or metastatic SCCHN, submitted in June 2008.

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.3 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 worldwide3,4 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 variety5 and nearly all express EGFR, which is critical for tumor growth.6 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.7 At least 75% of all head and neck cancers are attributed to its two major risk factors, smoking tobacco and alcohol consumption.8

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

References

1. Vermorken JB, et al. N Engl J Med 2008; 359:1116-27.
2. Herrero FR, et al. ESMO 2008; Abstract No: 693.
3. GLOBOCAN 2002 (http://www-dep.iarc.fr), accessed August 2008.
4. Vermorken JB, et al. J Clin Oncol 2007;25:(18S).
5. Hunter KD, et al. Nat Rev Cancer 2005;Feb;5(2):127-35.
6. Bourhis J & 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.
7. Forastiere A, et al. N Engl J Med 2001;345(26):1890-1900.
8. Hashibe M, et al. J Natl Inst 2007;99:777-89.

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 http://www.merckserono.net or 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 31,946 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.

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