Metastatic colorectal cancer: update of Erbitux labeling to patients with RAS wild-type tumors
Merck Serono has announced that the European Commission ( EU ) has approved the type II variation to amend the Erbitux ( Cetuximab ) product information, updating the indication for Erbitux to the treatment of patients with RAS wild-type metastatic colorectal cancer ( mCRC ).
The approval of the European Commission follows the positive opinion from the Committee for Medicinal Products for Human Use ( CHMP ) 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 ( OxaliPlatin and cetUximab in firSt-line treatment of mCRC ) study.
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 Erbitux, while patients with RAS mutant tumors may not.
In the updated product information, Erbitux is now 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 Erbitux with Oxaliplatin-containing chemotherapy is now extended to include patients with mutant RAS mCRC or for whom RAS mCRC status is unknown.
OPUS is a randomized, controlled, phase II trial, involving 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.
Colorectal cancer is the fourth most common cancer worldwide, with an estimated incidence of more than 1.2 million cases globally.
An estimated 608,000 deaths from colorectal cancer occur worldwide each year, accounting for 8% of all cancer deaths and making it the fourth most common cause of death from cancer.
Almost 60% of the cases occur in developed regions, and incidence and mortality rates are substantially higher in men than in women.
In Europe alone, an estimated 436,000 people develop colorectal cancer every year, with approximately 212,000 people dying from the disease annually.
Cetuximab is a IgG1 monoclonal antibody targeting the epidermal growth factor receptor ( 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 Cetuximab 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. ( Xagena )
Source: Merck Serono, 2013