UK's NICE Recommends Use Of Erbitux For Metastatic Colorectal Cancer Patients

Main Category: Colorectal Cancer
Article Date: 16 Jun 2009 - 3:00 PDT

email to a friend   printer friendly   view / write opinions   rate article

The United Kingdom's National Institute for Health and Clinical Excellence (NICE) has published a Final Appraisal Determination (FAD) recommending the use of the drug Erbitux® (cetuximab) in combination with chemotherapy as a first-line treatment for patients with metastatic (advanced) colorectal cancer (mCRC) who have met specific additional criteria(1) - presenting the possibility of potentially curative surgery.(2) The treatment is recommended for patients in whom the cancer has spread only to the liver and who have normal or 'wild-type' KRAS tumors.(1) In the UK, a recommendation by NICE is a prerequisite for funding of a medical treatment by the National Health Service.

"This is the second positive NICE recommendation for Erbitux in the last 12 months and represents really positive news for metastatic colorectal cancer patients in the UK especially as Erbitux is the only targeted therapy endorsed by NICE for the first-line treatment of the disease," said Dr. Wolfgang Wein, Executive Vice President, Oncology, Merck Serono, a division of Merck KGaA, Darmstadt, Germany. "We strongly believe that personalizing cancer care by tumor type through KRAS testing at diagnosis is essential in order to provide patients with the best possible outcomes such as potentially curative surgery while offering healthcare providers the most efficient use of resources." The evidence supporting NICE's decision includes the CRYSTALa study, published in the New England Journal of Medicine in April 2009, which demonstrated the efficacy of Erbitux in mCRC patients with KRAS wild-type tumors, representing up to 65% of patients3. The CELIMb study also supported the decision demonstrating that in KRAS wild-type patients, Erbitux plus chemotherapy achieved some of the highest response rates (shrinkage of tumor) observed in clinical trials. Because of this increase in response, mCRC patients with previously inoperable liver metastases were able to undergo liver surgery, thus increasing the potential for cure in four out of 10 patients in this setting.4

This followed the presentation at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO GI) earlier this year of an abstract outlining the potential economic savings that could result from routinely testing mCRC patients for their KRAS status at diagnosis to determine who would be most likely to benefit from treatment with Erbitux.5

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.6 Approximately 25% of patients present with metastatic disease,7and 5-year survival rates for patients with mCRC can be as low as 5%.8

The final NICE guidance is scheduled to be published in July and will be implemented within three months of publication

aCRYSTAL: Cetuximab combined with iRinotecan in first line therapY for metaSTatic colorectAL cancer

bCELIM: Randomized multicenter study ofCEtuximab plus FOLFOX or FOLFIRI in neoadjuvant treatment of non-resectable colorectal LIver Metastases

References

1. National Institute for Health and Clinical Excellence. Final Appraisal Determination: Cetuximab for the first-line treatment of metastatic colorectal cancer. June 2009.

2. Folprecht G et al. Ann Oncol 2005;16:1311 - 131.

3. Van Cutsem E, et al. N Engl J Med 2009;360:1408-17.

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

5. Shankaran V, et al. Data presented at ASCO GI Congress 2009; Abstract No: 298.

6. Parkin DM, et al. CA Cancer J Clin 2005;55:74-108.

7. Cunningham D & Findley M. Eur J Cancer 1993;29A(15):2077-9.

8. Macdonald JS. CA Cancer J Clin 1999;49(4):202-19.

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 and for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 71 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.

-- April 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

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, 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., Seattle, Washington, USA.

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

Source: Merck