Cetuximab, bevacizumab and panitumumab for the treatment of metastatic colorectal cancer after first-line chemotherapy

Bevacizumab (Avastin, Roche Products) is a recombinant monoclonal antibody that inhibits angiogenesis by targeting the biological activity of human vascular endothelial growth factor, which stimulates formation of new blood vessels in the tumour. The UK marketing authorisation states that bevacizumab 'in combination with fluoropyrimidine-based chemotherapy is indicated for the treatment of patients with metastatic carcinoma of the colon or rectum'. Fluoropyrimidines are anti-metabolite drugs which include 5-fluorouracil (5-FU), folinic acid, capecitabine and tegafur.

Bevacizumab is contraindicated in people who have hypersensitivity to the active substance or to any of the excipients. The summary of product characteristics (SPC) lists the following as special warnings and precautions for use: gastrointestinal perforations, gastrointestinal fistulae, wound healing complications, hypertension, reversible posterior leukoencephalopathy syndrome, proteinuria, thromboembolism (arterial and venous), haemorrhage (including pulmonary haemorrhage and haemoptysis), congestive heart failure, neutropenia, hypersensitivity reactions (including infusion reactions), osteonecrosis of the jaw and eye disorders. For full details of side effects and contraindications, see the SPC.

Bevacizumab is administered by intravenous infusion. The recommended dosage is 5 or 10 mg/kg of body weight once every 2 weeks or 7.5 or 15 mg/kg of body weight once every 3 weeks. The price of a 100-mg vial is £242.66, and a 400-mg vial is £924.40 (excluding VAT; BNF, edition 61). Costs may vary in different settings because of negotiated procurement discounts.

Cetuximab (Erbitux, Merck Serono) is a recombinant monoclonal antibody that blocks the human EGFR and inhibits the proliferation of cells that depend on activation of EGFR for growth. Cetuximab has a UK marketing authorisation for the treatment of patients with EGFR-expressing, KRAS wild-type metastatic colorectal cancer, in combination with irinotecan-based chemotherapy or FOLFOX (5-FU and folinic acid and oxaliplatin) or as a single agent in patients whose disease has failed to respond to oxaliplatin and irinotecan-based therapy, and who are intolerant to irinotecan.

Cetuximab is contraindicated in people with known severe (grade 3 or 4) hypersensitivity reactions to cetuximab. The SPC lists the following as special warnings and precautions for use: infusion-related reactions, respiratory disorders, skin reactions, electrolyte disturbances, neutropenia and cardiovascular disorders. For full details of side effects and contraindications, see the SPC.

Cetuximab is administered by intravenous infusion. The recommended dosage is an initial dose of 400 mg/m² of body surface area followed by 250 mg/m² once a week. The list price of a 20-ml vial (100-mg) is £178.10, and a 100-ml vial (500-mg) is £890.50 (excluding VAT; BNF, edition 61). The manufacturer of cetuximab has agreed with the Department of Health that the price to the NHS will be £136.50 for a 20-ml vial and £682.50 for a 100-ml vial. Because the reduced prices are in the public domain and are available across the NHS, all calculations in the economic model are based on these reduced prices. Costs may vary in different settings because of negotiated procurement discounts.

Panitumumab (Vectibix, Amgen) is a recombinant monoclonal antibody that blocks EGFR, inhibiting the growth of tumours expressing EGFR. It has a UK marketing authorisation as a 'monotherapy for the treatment of patients with EGFR-expressing metastatic colorectal cancer with non-mutated (wild-type) KRAS after failure of fluoropyrimidine-, oxaliplatin- and irinotecan-containing chemotherapy regimens'.

Panitumumab is contraindicated in people with severe hypersensitivity to the active substance or to any of the excipients and in people with interstitial pneumonitis or pulmonary fibrosis. The SPC lists the following as special warnings and precautions for use: 'dermatologic reactions, pulmonary complications, electrolyte disturbances, infusion-related reactions, acute renal failure and keratitis'. For full details of side effects and contraindications, see the SPC.

Panitumumab is administered by intravenous infusion. The recommended dosage is 6 mg/kg of body weight once every 14 days. The price of a 100-mg vial is £379.29, and a 400-mg vial is £1,517.16 (excluding VAT; BNF, edition 61). Costs may vary in different settings because of negotiated procurement discounts.