Erbitux

cetuximab

This is a summary of the European Public Assessment Report (EPAR). It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the studies performed, to reach their recommendations on how to use the medicine.
If you need more information about your medical condition or your treatment, read the Package Leaflet (also part of the EPAR) or contact your doctor or pharmacist. If you want more information on the basis of the CHMP recommendations, read the Scientific Discussion (also part of the EPAR).

What is Erbitux?

Erbitux is a solution for infusion (drip into a vein) that contains the active substance cetuximab.

What is Erbitux used for?

Erbitux is used to treat the following types of cancer:

• metastatic cancer of the colon or rectum (large intestine). 'Metastatic' means that the cancer has spread to other parts of the body. Erbitux is used in patients whose tumour cells have a protein on their surface called epidermal growth factor receptor (EGFR) and contain a ‘wild-type’ (non-mutated) gene called 'KRAS'. Erbitux is used together with other anticancer medicines, or on its own when previous cancer treatment containing oxaliplatin and irinotecan has failed and the patient cannot receive irinotecan;
• 'squamous cell' cancers of the head and neck. These types of cancer affect the cells of the lining of the mouth or the throat, or of organs such as the larynx (voice box). In locally advanced cancer (when the tumour has grown but has not spread), Erbitux is given in combination with radiotherapy (radiation therapy). In cancer that is recurrent (when it has come back after previous treatment) or metastatic, Erbitux is used with a ‘platinum-based’ anticancer medicine combination (including medicines such as cisplatin or carboplatin).

The medicine can only be obtained with a prescription.

How is Erbitux used?

Erbitux should only be given by doctors who have experience in the use of anticancer medicines.

Before receiving Erbitux for the first time, the patient must be given an antihistamine and a corticosteroid to prevent an allergic reaction. This is also recommended for all subsequent infusions.

Erbitux is given once a week. The first infusion is given at a dose of 400 mg per square metre body surface area (calculated using the patient’s height and weight) over two hours. The following infusions are 250 mg/m2 given over one hour. When it is used on its own or with other anticancer medicines, Erbitux is continued for as long as the patient responds. When it is used with radiotherapy, Erbitux is started one week before the radiotherapy starts and continued until the radiotherapy has finished.

How does Erbitux work?

The active substance in Erbitux, cetuximab, is a monoclonal antibody. A monoclonal antibody is an antibody (a type of protein) that has been designed to recognise and attach to a specific structure (called an antigen) in the body. Cetuximab has been designed to attach to EGFR, which can be found on the surface of some tumour cells. As a result, the tumour cells can no longer receive the messages needed for growth, progression and spread. Between 79 and 89% of colorectal cancers and more than 90% of squamous cell cancers of the head and neck have EGFR on their cell surfaces.

How has Erbitux been studied?

For metastatic cancer of the colon or rectum, Erbitux was studied in five main studies:

• two studies involved 1,535 patients who had not received chemotherapy before, looking at the effects of adding Erbitux to a treatment combination containing either irinotecan or oxaliplatin;
• three studies involved 2,199 patients whose disease had got worse while they were on previous treatment including irinotecan, oxaliplatin or both, or who could not receive these medicines.

For cancers of the head and neck, Erbitux was investigated in two main studies:

• the first study involved 424 patients with locally advanced cancer, looking at the effects of adding Erbitux to radiotherapy;
• the second study involved 442 patients with recurrent or metastatic cancer, looking at the effects of adding Erbitux to a platinum-based anticancer medicine combination.

All of the studies looked at how long the patients lived without their cancer getting worse or how long they survived. Most of the studies looked at the results separately in patients whose tumours had wild-type KRAS and patients whose tumours had mutated KRAS. In tumour cells, KRAS stimulates tumour growth when it is mutated.

What benefit has Erbitux shown during the studies?

In the studies of cancer of the colon or rectum, the patients who had wild-type KRAS in their tumours lived for longer without their disease getting worse when they received Erbitux:

• in patients who had not received chemotherapy before, patients lived for longer without their disease getting worse when they received Erbitux in addition to chemotherapy. This included chemotherapy including irinotecan (9.9 months compared with 8.7 months, on average) and including oxaliplatin (7.7 months compared with 7.2 months, on average);
• the first study in patients who had taken chemotherapy before did not look at KRAS mutations, but in the other two studies, patients with wild-type KRAS in their tumours lived for longer without their disease getting worse when Erbitux was added to their treatment. Patients who had failed both oxaliplatin and irinotecan treatment lived for an average of 3.6 months without their disease getting worse with Erbitux, compared with 1.9 months in those receiving best supportive care alone (the treatment of symptoms but not the cancer itself). Patients who had failed oxaliplatin treatment lived for an average of 4.0 months without their disease getting worse with Erbitux plus irinotecan, compared with 2.6 months in those receiving irinotecan alone.

In locally advanced head and neck cancers, the patients lived for longer without their disease getting worse when Erbitux was added to radiotherapy (24.4 months compared with 14.9 months, on average). In recurrent or metastatic head and neck cancer, survival was longer when Erbitux was added to a platinum-based anticancer medicine combination (10.1 months compared with 7.4 months, on average).

What is the risk associated with Erbitux?

The most common side effects with Erbitux (seen in more than 1 patient in 10) are skin reactions such as rash, hypomagnesaemia (low blood magnesium levels), reactions linked to the infusion (such as fever, chills, dizziness and difficulty breathing), mucositis (inflammation of the lining of the mouth) and raised levels of some liver enzymes. Skin reactions are seen in more than 80% of patients. For the full list of all side effects reported with Erbitux, see the Package Leaflet.

Erbitux should not be used in people who are very hypersensitive (allergic) to cetuximab.

Erbitux can be associated with severe reactions during the infusion, so the patients must be monitored carefully while the medicine is being given.

Why has Erbitux been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Erbitux’s benefits are greater than its risks for the treatment of patients with EGFR-expressing, KRAS wild-type metastatic colorectal cancer, and patients with squamous cell cancer of the head and neck. The Committee recommended that Erbitux be given marketing authorisation.

Other information about Erbitux:

The European Commission granted a marketing authorisation valid throughout the European Union for Erbitux to Merck KGaA on 29 June 2004. The marketing authorisation was renewed on 29 June 2009.

This EPAR was last updated on 09/12/2011 .

More detail is available in the Summary of Product Characteristics

Product details

Publication details

Product information

24/10/2011  Erbitux -EMEA/H/C/000558 -II/0044/G

Contents

• Annex I - Summary of product Characteristics
• Annex IIA - Manufacturing Authorisation Holder responsible for Batch Release
• Annex IIB - Conditions of the Marketing Authorisation
• Annex IIIA - Labelling
• Annex IIIB - Package Leaflet

Please note that the size of the above document can exceed 50 pages.

You are therefore advised to be selective about which sections or pages you wish to print.

Pharmaco-therapeutic Group

Antineoplastic agents

Therapeutic Indication

Erbitux is indicated for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing, KRAS wild-type metastatic colorectal cancer

• in combination with irinotecan-based chemotherapy or FOLFOX4

• as a single agent in patients who have failed oxaliplatin- and irinotecan-based therapy and who are intolerant to irinotecan.

Erbitux is indicated for the treatment of patients with squamous cell cancer of the head and neck

• in combination with radiation therapy for locally advanced disease

• in combination with platinum-based chemotherapy for recurrent and/or metastatic disease.

Changes since initial authorisation of medicine

Initial Marketing authorisation documents