Pazopanib for the first-line treatment of advanced renal cell carcinoma

Pazopanib (Votrient, GlaxoSmithKline) is an orally administered tyrosine kinase inhibitor. It inhibits vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors on cancer cells, vascular endothelial cells and pericytes, stopping the proliferation of tumour cells and the development of tumour blood vessels. Pazopanib has a conditional marketing authorisation for 'the first-line treatment of advanced renal cell carcinoma and for patients who have received prior cytokine therapy for advanced disease'. The conditional marketing authorisation is linked to the provision of further data including the outcome of the ongoing head-to-head non-inferiority trial of pazopanib versus sunitinib in patients with advanced renal cell carcinoma (COMPARZ). Only the indication for pazopanib for the first-line treatment of advanced renal cell carcinoma is within the remit of the appraisal.

Pazopanib is contraindicated in people who have hypersensitivity to the active substance or to any of the excipients, and people with severe hepatic impairment. The summary of product characteristics lists the adverse events that may be associated with pazopanib treatment, the most common being diarrhoea, hair colour changes, hypertension, nausea, anorexia, vomiting, fatigue, taste disturbance or loss of taste, and abnormal liver function. For full details of side effects and contraindications, see the summary of product characteristics.

Pazopanib is administered orally. The recommended dosage is 800 mg once daily. The dose may be adjusted in steps of 200 mg according to tolerability in order to manage adverse reactions but should not exceed 800 mg. The price for a pack of 400 mg tablets (30 tablets per pack) is £1,121.00 (MIMS, November 2010). The daily cost of pazopanib is £74.73 as stated by the manufacturer. The manufacturer of pazopanib has agreed a 2-part patient access scheme with the Department of Health. Part A of the patient access scheme provides a 12.5% discount from the list price. Therefore, the daily acquisition cost of pazopanib is £65.39. Part B of the patient access scheme, the details of which are 'commercial in confidence', offers a future rebate linked to the outcome of the head-to-head COMPARZ trial. The Department of Health considered that this patient access scheme does not constitute an excessive administrative burden on the NHS.