The European Commission has approved and amendment of cetuximab (Erbitux?; Merck Serono/Merck*) product information, updating the indication for cetuximab to the treatment of patients with RAS wild-type metastatic colorectal cancer (mCRC).
Colorectal cancer or CRC is the fourth most common cancer worldwide, with an estimated incidence of more than 1.2 million cases globally.[1] Ar the same time, there are an estimated 608,000 deaths from CRC occurring worldwide each year, accounting for 8% of all cancer deaths and making it the fourth most common cause of death from cancer.[1] Almost 60% of the cases occur in developed regions, and incidence and mortality rates are substantially higher in men than in women.[1] In Europe alone, an estimated 436,000 people develop CRC every year, with approximately 212,000 people dying from the disease annually.[2]
Cetuximab will now be indicated for the treatment of patients with EGFR-expressing, RAS wild-type mCRC in combination with irinotecan-based chemotherapy, in 1st line in combination with FOLFOX?
Cetuximab is a first-in-class and highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor or EGFR. As a monoclonal antibody, the mode of action of the drug 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. Cetuximab 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.
Label extention
Cetuximab has already obtained market authorization in over 90 countries for the treatment of colorectal cancer and for the treatment of squamous cell carcinoma of the head and neck (SCCHN). The added approval of the European Commission is based on a positive opinion from the Committee for Medicinal Products for Human Use or CHMP issued in November 21, 2013 and is based on the totality of data emerging on the role of mCRC RAS tumor status in the benefit-risk profile of the drug. The approval primarily refers to new biomarker data from the OPUS-study (OxaliPlatin and cetUximab in firSt-line treatment of mCRC).[3]
The OPUS-study is a randomized, controlled, Phase II trial, which involved 337 mCRC patients, 179 with KRAS wild-type (exon 2) tumors, demonstrating the efficacy of cetuximab plus FOLFOX-4 (oxaliplatin-based therapy) versus FOLFOX-4 alone.[4] Results of a RAS tumor status analysis will be presented at the upcoming Gastrointestinal Cancers Symposium (ASCO GI), which ail be held in January 16 – 18, 2014, in San Francisco, California, U.S.
Benefiting patients
In recent analyses of studies evaluating monoclonal anti-epidermal growth factor receptor (EGFR) antibodies, such as cetuximab, tumor samples of patients with KRAS wild-type tumor status (exon 2) were assessed for additional RAS mutations (defined as mutations in exons 3 or 4 of KRAS and/or exons 2, 3 or 4 of NRAS). The results from these studies suggest that patients with RAS wild-type tumors may benefit from treatment with cetuximab, while patients with RAS mutant tumors may not.
“We fully endorse the update to the indication of Erbitux in metastatic colorectal cancer, as it will provide further guidance to physicians who manage patients with colorectal cancer,” noted Belen Garijo, President and CEO of Merck Serono. “We will now be working with the regulatory agencies to effectively communicate the implications of this label change to healthcare professionals and patients.”
Updated product information
In the updated product information, cetuximab will now be indicated for the treatment of patients with EGFR-expressing, RAS wild-type mCRC in combination with irinotecan-based chemotherapy, in 1st line in combination with FOLFOX, or as a single agent in patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to irinotecan. In this label change, the existing contraindication for the combination of cetuximab with oxaliplatin-containing chemotherapy is now extended to include patients with mutant RAS mCRC or for whom RAS mCRC status is unknown.
For more information
[1] Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010 Dec 15;127(12):2893-917. doi: 10.1002/ijc.25516. [Article][PubMed]
[2] Ferlay J, Parkin DM, Steliarova-Foucher E.Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer. 2010 Mar;46(4):765-81. doi: 10.1016/j.ejca.2009.12.014. Epub 2010 Jan 29.[Article][PubMed]
[3]Tejpar S, et al. Accepted at 2014 Gastrointestinal Cancers Symposium, January 16-18, 2014.
[4] Bokemeyer C, Bondarenko I, Hartmann JT, de Braud F, Schuch G, Zubel A, et al. Efficacy according to biomarker status of cetuximab plus FOLFOX-4 as first-line treatment for metastatic colorectal cancer: the OPUS study. Ann Oncol. 2011 Jul;22(7):1535-46. doi: 10.1093/annonc/mdq632. Epub 2011 Jan 12. [Article][PubMed]
* Merck has licensed the right to market Erbitux outside the U.S. and Canada from ImClone LLC, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. In Japan, ImClone, 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.
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