2 The technology

2.1 Trastuzumab (Herceptin, Roche Products) is a recombinant humanised IgG1 monoclonal antibody directed against HER2. Trastuzumab in combination with capecitabine or 5-fluorouracil and cisplatin is indicated for the treatment of patients with HER2-positive metastatic adenocarcinoma of the stomach or gastro-oesophageal junction who have not received prior anticancer treatment for their metastatic disease. Trastuzumab is approved for use only in patients with metastatic gastric cancer whose tumours have HER2 overexpression as defined by immunohistochemistry (IHC)2 positive and a confirmatory fluorescence in situ hybridisation (FISH) positive result, or IHC3 positive, as determined by an accurate and validated assay. On 6 August 2010, the marketing authorisation for trastuzumab was revised to include silver in situ hybridisation (SISH) testing as another method for confirming HER2 overexpression. Because of the timing of the revision, SISH testing was not considered in this appraisal. For further details see the summary of product characteristics.

2.2 Trastuzumab is associated with cardiotoxicity. The summary of product characteristics states that all patients should have baseline cardiac assessment before starting treatment. Cardiac function should be further monitored during treatment (for example, every 12 weeks). The summary of product characteristics also states that caution should be taken in treating people with symptomatic heart failure, a history of hypertension, or documented coronary artery disease. For full details of side effects and contraindications, see the summary of product characteristics.

2.3 Trastuzumab is administered at an initial loading dose of 8 mg/kg body weight. The recommended maintenance dose at 3-weekly intervals is 6 mg/kg body weight, beginning 3 weeks after the loading dose. It is given as an intravenous infusion over 90 minutes. If the initial loading dose is well tolerated, the subsequent doses can be administered as 30-minute infusions. As long as treatment is tolerated, it can be given until disease progression.

2.4 The net price of a 150-mg vial of trastuzumab is £407.40 (excluding VAT; 'British national formulary' [BNF] edition 59). For a patient weighing 62 kg, four vials are required for the first loading dose and three vials for each subsequent dose. Assuming that excess trastuzumab is wasted, the drug cost of eight infusions of trastuzumab (the median number of infusions in the regulatory trial) is £10,185. Costs may vary in different settings because of negotiated procurement discounts.

  • National Institute for Health and Care Excellence (NICE)