2 The technology

2 The technology

Description of the technology

Cetuximab (Erbitux; Merck) is a recombinant monoclonal antibody that blocks human epidermal growth factor receptor (EGFR). It inhibits the proliferation of cells that depend on EGFR activation for growth.

Marketing authorisation

Cetuximab has a UK marketing authorisation 'for the treatment of patients with squamous cell cancer of the head and neck… in combination with platinum-based chemotherapy for recurrent and/or metastatic disease'.

Adverse reactions

Very common adverse reactions with cetuximab include skin reactions, which occur in more than 80% of patients, and low blood magnesium levels, mild or moderate infusion-related reactions (such as fever, chills, nausea, vomiting, headache, dizziness or shortness of breath), inflammation of the lining of the digestive tract, and raised liver enzymes, which all occur in 10% or more of patients. Common side effects (occurring in 1% or more and less than 10% of patients) include severe infusion-related reactions (including anaphylactic reactions), dehydration, low blood calcium levels, anorexia, headache, conjunctivitis, fatigue, diarrhoea, nausea and vomiting. Cetuximab in combination with platinum-based chemotherapy may increase the frequency of severe leukopenia or severe neutropenia, and this may lead to a higher rate of infectious complications than platinum-based chemotherapy alone. For full details of adverse reactions and contraindications, see the summary of product characteristics.

Recommended dose and schedule

Cetuximab is administered intravenously. It is used in combination with platinum-based chemotherapy followed by cetuximab as maintenance therapy until disease progression. The initial loading dose is 400 mg/m2 body surface area (BSA) given at a rate not exceeding 5 mg/minute. Subsequent weekly maintenance doses are 250 mg/m2 BSA each.

Price

The list price of cetuximab is £178.10 for a 5 mg/ml 20‑ml vial and £890.50 for a 5 mg/ml 100‑ml vial (excluding VAT; British national formulary [BNF] online, accessed February 2017). Assuming that vials are not shared among patients, a person with a BSA of 1.75 m2 would have 7 vials per loading dose and 5 vials per maintenance dose, equating to a cost of £1,246.70 for the loading dose and £890.50 for each maintenance dose.

The pricing arrangement considered during guidance development was one in which the company (Merck) had agreed a patient access scheme with the Department of Health. This scheme would have provided a simple discount to the list price of cetuximab with the discount applied at the point of purchase or invoice. The Department of Health considered that this patient access scheme would not constitute an excessive administrative burden on the NHS. This has now been replaced by a commercial access agreement between the company and NHS England, which incorporates this same simple discount applied at the point of purchase or invoice of all cetuximab but also includes additional and separate commercial arrangements. The financial terms of the agreement are commercial in confidence.

  • National Institute for Health and Care Excellence (NICE)