3.1 Lapatinib (Tyverb, GlaxoSmithKline) is a protein kinase inhibitor that blocks the tyrosine kinase components of the epidermal growth factor receptors (ErbB1 and ErbB2), which are implicated in the growth of various tumours. Lapatinib has conditional marketing authorisation (that is, further evidence on this medicinal product is being awaited) in the UK. Lapatinib is 'indicated for the treatment of patients with breast cancer, whose tumours overexpress HER2 (ErbB2); in combination with an aromatase inhibitor for postmenopausal women with hormone receptor positive metastatic disease, not currently intended for chemotherapy'. The summary of product characteristics (SPC) states that 'patients in the registration study were not previously treated with trastuzumab or an aromatase inhibitor'.
3.2 The SPC states that the most common adverse reactions during therapy with lapatinib are diarrhoea, nausea, vomiting and rash. For full details of adverse reactions and contraindications, see the SPC.
3.3 Lapatinib is administered orally at a dosage of 1500 mg (six tablets) per day. The net price per pack of 84 tablets is £965.16 (excluding VAT; British national formulary [BNF], edition 62). The acquisition cost for a lifetime of treatment with lapatinib plus the aromatase inhibitor letrozole is £28,212 (£27,024 for lapatinib and £1188 for letrozole), assuming a mean treatment duration of 55.2 weeks and excluding administration costs. Costs may vary in different settings because of negotiated procurement discounts.
3.4 Trastuzumab (Herceptin, Roche Products) is a recombinant humanised IgG1 monoclonal antibody directed against HER2. Trastuzumab is indicated for the treatment of patients with HER2+ metastatic breast cancer 'in combination with an aromatase inhibitor for the treatment of postmenopausal patients with hormone-receptor positive metastatic breast cancer, not previously treated with trastuzumab'.
3.5 The SPC states that the most common adverse reactions associated with trastuzumab in combination with chemotherapy are cardiotoxicity, infusion-related reactions, haematotoxicity (in particular neutropenia) and pulmonary events. In the clinical trials, patients receiving trastuzumab had to have a left ventricular ejection fraction of at least 55% and to have cardiac monitoring every 4 months. For full details of adverse reactions and contraindications, see the SPC.
3.6 The recommended dosage of trastuzumab is either a loading dose of 4 mg/kg by intravenous infusion followed by a weekly maintenance dose of 2 mg/kg until disease progression, or a loading dose of 8 mg/kg by intravenous infusion followed by 3-weekly maintenance doses of 6 mg/kg until disease progression. The net price per 150 mg vial is £407.40 (excluding VAT; BNF 62). Assuming an average patient weight of 67 kg, a mean treatment period of 15 months and excluding administration, monitoring and wastage costs, the acquisition cost for a lifetime of treatment with trastuzumab plus anastrozole is £26,018 (£24,852 for trastuzumab and £1166 for anastrozole) for a weekly schedule and £26,832 (£25,666 for trastuzumab and £1166 for anastrozole) for a 3-weekly schedule. Costs may vary in different settings because of negotiated procurement discounts.