2 The technology
2.1 Aflibercept (Zaltrap, Sanofi) is a recombinant human fusion protein that blocks the vascular endothelial growth factor (VEGF) pathway by preferentially binding to VEGF-A, VEGF-B and placental growth factor, which play an important role in the formation of new blood vessels in solid tumours (angiogenesis). By preventing these factors from activating their endogenous receptors, aflibercept interferes with the process by which blood vessels and capillaries expand into tumours (vascularisation), and so inhibits tumour growth. Aflibercept in combination with folinic acid/5-fluorouracil/irinotecan (FOLFIRI) (that is, in combination with irinotecan and fluorouracil-based therapy) has a UK marketing authorisation 'for the treatment of adults with metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing regimen'. The summary of product characteristics states that aflibercept should be administered as an intravenous infusion over 1 hour at a dose of 4 mg/kg of body weight, followed by the FOLFIRI regimen, every 2 weeks until the disease progresses or unacceptable toxicity occurs.
2.2 The summary of product characteristics lists the following most common adverse reactions (according to the Common Terminology Criteria for Adverse Events v3.0) for aflibercept plus FOLFIRI in order of decreasing frequency: leukopenia, diarrhoea, neutropenia, proteinuria, increased plasma activity of aspartate aminotransferase, stomatitis, fatigue, thrombocytopenia, increased plasma activity of alanine aminotransferase, hypertension, weight loss, decreased appetite, epistaxis, abdominal pain, dysphonia, increased serum creatinine and headache. For full details of adverse reactions and contraindications, see the summary of product characteristics.
2.3 The manufacturer states that the net price of a vial of 100 mg aflibercept is £295.65, and the net price of a vial of 200 mg aflibercept is £591.30. The cost per patient will vary with dose adjustment and treatment duration. The manufacturer of aflibercept (Sanofi) has agreed a patient access scheme with the Department of Health that makes aflibercept available with a discount. The size of the discount is commercial in confidence. The Department of Health considered that this patient access scheme does not constitute an excessive administrative burden on the NHS. Costs may vary in different settings because of negotiated procurement discounts.