Bevacizumab (Avastin, Roche Products) is a recombinant humanised monoclonal IgG1 antibody that acts as an angiogenesis inhibitor. It targets the biological activity of human vascular endothelial growth factor, which stimulates new blood vessel formation in the tumour. Bevacizumab is licensed in the UK in combination with intravenous 5-FU/FA with or without irinotecan for first-line treatment of patients with metastatic carcinoma of the colon or rectum.
Bevacizumab is contraindicated in patients who are pregnant, have untreated central nervous system metastases, have hypersensitivity to the active substance or to any of the excipients, or have hypersensitivity to products derived from Chinese hamster ovary cell cultures or other recombinant human or humanised antibodies. The summary of product characteristics (SPC) lists the following complications that may be associated with bevacizumab treatment: gastrointestinal perforation, wound-healing problems, hypertension, proteinuria, arterial thromboembolism, haemorrhage and cardiomyopathy. For full details of side effects and contraindications, see the SPC.
Bevacizumab is administered as an intravenous infusion at a dose of 5 mg/kg body weight once every 14 days. Bevacizumab treatment is recommended until there is underlying disease progression. Bevacizumab is available in 100-mg and 400-mg vials at net prices of £242.66 and £924.40 respectively (excluding VAT; BNF, edition 51). If vial wastage is assumed, a 75-kg person would receive a single 400-mg vial of bevacizumab per dose, equating to a cost of £924.40. Patients in the key registration trial received an average of 18.2 doses, equating to an average total cost of drug acquisition of £16,824.08 per patient. Costs may vary in different settings because of negotiated procurement discounts.
Cetuximab (Erbitux, Merck Pharmaceuticals) is a recombinant monoclonal antibody that blocks the human epidermal growth factor receptor (EGFR) and thus inhibits the proliferation of cells that depend on EGFR activation for growth. Cetuximab is licensed in the UK in combination with irinotecan for the treatment of patients with EGFR-expressing metastatic colorectal cancer after failure of cytotoxic therapy that included irinotecan.
The UK marketing authorisation stipulates that before being treated with cetuximab patients should be tested to identify whether or not the tumour is expressing EGFR. This is currently done using the commercially available DakoCytomation kit, which uses immunohistochemistry to identify EGFR expression (£995.00 for a set of 35 tests [information supplied by manufacturer]).
One common side effect of cetuximab therapy is the development of an acne-like rash. The SPC notes that if a patient experiences a grade 3 or 4 skin reaction cetuximab treatment must be interrupted, with treatment being resumed only if the reaction resolves to grade 2. In addition, the SPC lists infusion-related reactions and respiratory disorders that may be associated with treatment with cetuximab. For full details of side effects and contraindications, see the SPC.
Cetuximab is given as an intravenous infusion with an initial loading dose of 400 mg/m2 of body surface area and subsequent weekly doses of 250 mg/m2. Cetuximab treatment is recommended until there is underlying disease progression. Cetuximab is provided in 50-ml vials containing 2 mg cetuximab per ml. The net price for a 50-ml vial is £136.50 (excluding VAT; BNF 51). Assuming vial wastage, an average person with a body surface area of 1.75 m2 would receive 7 vials per loading dose and 5 vials per maintenance dose, equating to a cost of £955.50 for the loading dose and £682.50 for each maintenance dose. Patients in the key registration trial received an average of 16.8 doses, equating to an average total drug acquisition cost of £11,739 per patient. Costs may vary in different settings because of negotiated procurement discounts.