Merck KGaA: New Data Reinforce Consistent Efficacy Profile of Erbitux in First-Line mCRC Patients with KRAS Wild-Type Tumors

DARMSTADT, Germany, January 14, 2009 – New data presented today at the 2009 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) in San Francisco add further evidence to the enhanced efficacy of Erbitux® (cetuximab) in metastatic colorectal cancer (mCRC) patients with KRAS wild-type tumors.

The CECOGa/CORE1.2.001 study, a randomized Phase II trial investigating the influence of KRAS status on the efficacy of Erbitux in combination with FOLFOX or FOLFIRI in the first-line treatment of 117 mCRC patients, provided a response rate (RR) of 53% in patients with KRAS wild-type tumors versus 36% in those with mutant tumors. The study also showed a trend towards improved overall survival (OS) in patients with KRAS wild-type tumors – 24.4 months for patients with KRAS wild-type tumors vs. 16.7 months for patients with KRAS mutant tumors (p=0.057).1

“It is really exciting to see such a consistent efficacy profile for Erbitux in patient populations defined by KRAS mutational status,” commented Prof Thomas Brodowicz from the University Hospital of Vienna, Austria, lead investigator of the CECOG/CORE1.2.001 study. “This further highlights the absolute necessity to define mCRC according to the KRAS status of the tumor in order to determine the most effective treatment strategy and to provide patients with the best possible outcomes.”

The results of the CECOG/CORE1.2.001 study support the pivotal Erbitux trials – the randomized Phase III study CRYSTALb, also presented at this meeting, and OPUSc, recently published in the Journal of Clinical Oncology. Patients receiving Erbitux in the CRYSTAL and OPUS trials who had KRAS wild-type tumors showed similar response rates to those in the CECOG/CORE1.2.001 study, at 59%2 and 61%,3 respectively.

The outcomes of the randomized CELIMd trial, also presented at ASCO GI, further support the data presented from the CRYSTAL and CECOG/CORE1.2.001 studies, which showed that the addition of Erbitux to standard chemotherapy in patients with unresectable liver metastases leads to high response rates. In the CELIM study, 79% of patients with KRAS wild-type tumors experienced distinct tumor shrinkage, and of these patients, 42% were able to undergo surgical resection and 35% were able to have the tumor completely removed (R0 resection).4

“The data demonstrating the efficacy of Erbitux in KRAS wild-type mCRC tumors are really mounting up now and for physicians this can only help ease the treatment decision-making process,” commented Dr. Wolfgang Wein, Executive Vice President, Oncology, Merck Serono. “Tailoring treatment for mCRC is now a reality. Through a simple diagnostic test, patients can be provided with a treatment that is most likely to succeed in their tumor type.”

More than 370,000 people develop colorectal cancer in Europe every year, accounting for 13% of the total cancer burden and around 200,000 deaths.5 Around a quarter of CRC patients present with metastatic disease6 and for these patients survival rates are as low as 5%.7 Approximately 65% of mCRC patients have KRAS wild-type tumors.8

a CECOG: Central European Cooperative Oncology Group
b CRYSTAL: Cetuximab combined with iRinotecan in first-line therapY for metaSTatic colorectAL cancer
c OPUS: OxaliPlatin and cetUximab in firSt-line treatment of mCRC
d CELIM: Randomized multicenter study of CEtuximab plus FOLFOX or FOLFIRI in neoadjuvant treatment of non-resectable colorectal LIver Metastases

References

1. Brodowicz T, et al. ASCO GI 2009; Abstract No: 381.

2. Rougier P, et al. ASCO GI 2009; Abstract No: 443.

3. Bokemeyer C, et al. J Clin Oncol 2008; published online ahead of print Dec 29 (doi:10.1200/JCO.2008.20.8397).

4. Folprecht G, et al. ASCO GI 2009; Abstract No: 296.

5. Parkin DM, et al. CA Cancer J Clin 2005;55:72-108.

6. Cunningham D and Findley M. Eur J Cancer 1993;29A(15):2077-2079.

7. Macdonald JS. CA Cancer J Clin 1999;49(4):202-219.

8. Van Cutsem E, et al. ESMO 2008; Abstract No: 710.

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 76 countries. It has been approved for the treatment of colorectal cancer in 75 countries so far: Argentina, Australia, Belarus, Canada, Chile, China, Colombia, Costa Rica, Croatia, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Hong Kong, Iceland, India, Indonesia, Israel, Japan, Kazakhstan, Kuwait, Lebanon, Liechtenstein, Malaysia, Mexico, Moldova, New Zealand, Nicaragua, Norway, Oman, Pakistan, 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. 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. Apart from the European Union label, 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, Iceland, Japan, Lebanon, Liechtenstein, Mexico, Moldova, New Zealand, Nicaragua, Norway, 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 70 countries: Argentina, Australia, Belarus, Brazil, Canada, Chile, Colombia, Costa Rica, Croatia, El Salvador, the European Union, Guatemala, Hong Kong, Iceland, India, Indonesia, Israel, Kazakhstan, Kuwait, Lebanon, Liechtenstein, Malaysia, Mexico, Moldova, New Zealand, Nicaragua, Norway, Oman, Pakistan, 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, Moldova, 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. In the European Union, the license was updated in November 2008 for the first-line use in combination with platinum-based chemotherapy in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

Merck licensed the right to market Erbitux outside the US and Canada from ImClone Systems, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. In Japan, ImClone Systems Incorporated, 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 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 KRAS
KRAS is a gene that codes for a protein that plays an important role in the epidermal growth factor receptor (EGFR) pathway – a complex signaling cascade that is involved in the development and progression of cancer. The KRAS protein regulates other proteins downstream in the EGFR signaling pathway that are associated with tumor survival, angiogenesis, proliferation and metastasis.


Contact
Phyllis Carter
Phone +49 6151 72-7144
 

Posted: January 2009

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