NICE Recommends Use Of Cetuximab (Erbitux(R)) For UK Bowel Cancer Patients

NICE Recommends Use Of Cetuximab (Erbitux(R)) For UK Bowel Cancer Patients

The National Institute for Health and Clinical Excellence (NICE) has today published a Final Appraisal Determination (FAD) recommending the use of the drug cetuximab (Erbitux®) in combination with chemotherapy as a 1st-line treatment for patients with metastatic (advanced) colorectal cancer (mCRC) who have met specific additional criteria1* - 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 'wild-type' (unmutated) KRAS‡ tumours.1 Up to 65% of patients have wild-type KRAS tumours.3

Don Cowling, Managing Director of Merck Serono UK, the manufacturer of cetuximab said: "NICE's FAD for cetuximab for use in advanced colorectal cancer is the second positive recommendation for the drug that NICE has published in the last twelve months. In June 2008, NICE issued a recommendation for cetuximab use in the treatment of locally advanced squamous cell cancer of the head and neck♦. We are delighted that this therapy will now also be available to appropriate colorectal cancer patients on the NHS."

The evidence supporting NICE's decision includes the CRYSTAL† study, published in the New England Journal of Medicine in April 2009, which demonstrated the efficacy of cetuximab in mCRC patients with wild-type KRAS tumours. This followed the presentation at the ASCO-GI conference earlier this year of an article outlining the potential economic savings that could result from routinely testing mCRC patients for their KRAS status to determine which patients would be most likely to benefit from treatment with cetuximab.3,4

Bowel cancer is the third most common cancer in the UK, with more than 36,000 people diagnosed each year.5

The final NICE guidance is scheduled to be published in July and will be implemented within three months of publication. The full NICE FAD for the use of Erbitux® in the treatment of advanced colorectal cancer can be found at http://www.nice.org.uk.

* For full details of criteria, visit NICE website (see above)

About KRAS

The KRAS gene codes for a protein involved in the EGFR pathway - a complex pathway involved in the development and progression of cancer. In KRAS wild-type tumours, the KRAS protein is only activated in response to certain stimuli, such as EGFR signalling. Erbitux® works by blocking the EGFR signalling pathway, preventing KRAS activation, and subsequent tumour growth. In mutant KRAS tumours, the KRAS protein is permanently activated (regardless of EGFR signalling), therefore the inhibitory effect of Erbitux® is diminished in these cases.

♦Cetuximab in combination with radiotherapy is recommended by NICE as a treatment option only for patients with locally advanced squamous cell cancer of the head and neck whose Karnofsky performance-status score is 90% or greater and for whom all forms of platinum-based chemoradiotherapy treatment are contraindicated

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

About Erbitux

Erbitux® is a first-in-class 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 tumour cells and the spread of tumours to new sites. It is also believed to inhibit the ability of tumour cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumours, which appears to lead to an overall suppression of tumour growth. The most commonly reported side effect with Erbitux is an acne-like skin rash that seems to be correlated with a response to therapy. Infusion-related reactions occur with mild to moderate symptoms in more than 10% of patients and with severe symptoms in more than 1% of patients.

Erbitux has already obtained market authorisation 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.

- 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 commercialise 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.

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.: Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates. Ann Oncol 2005; 16:1311-131

3. Van Cutsem E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009;360:1408-17

4. Shankaran V, et al. Economic implications of Kras testing in metastatic colorectal cancer (mCRC). American Society of Clinical Oncology Gastrointestinal Cancers Symposium Abstract 298. 2009. http://www.asco.org

5. Cancer Research UK website: http://info.cancerresearchuk.org/cancerstats/types/bowel/ (accessed April 2009)

Source
Merck Serono

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