3 The technology

3 The technology

3.1 Imatinib (Novartis) is a signal-transduction inhibitor designed to selectively inhibit certain classes of tyrosine kinase that include the c-KIT receptor expressed in GIST. Imatinib binds to activated c-KIT receptors and blocks the cell signalling pathway to prevent uncontrolled cell proliferation. Imatinib was first licensed for the treatment of chronic myeloid leukaemia, for which NICE guidance exists (NICE Technology Appraisal Guidance No. 70 'Imatinib for chronic myeloid leukaemia').

3.2 Imatinib received European marketing authorisation in May 2002 for the treatment of adult patients with KIT (CD117)-positive unresectable and/or metastatic malignant GIST. Licensing approval was based largely on a single, uncontrolled phase II study in 147 patients. Recent developments in pathology suggest that a small minority of GISTs that test negative for the c-KIT receptor may also respond to imatinib. However, the evidence to support this is currently limited and the UK marketing authorisation for imatinib does not include the treatment of this group of tumours.

3.3 The manufacturer's summary of product characteristics recommends oral imatinib at a dose of 400 mg/day for the treatment of unresectable and/or metastatic GIST, to be taken with a large glass of water at meal times. The licence also states that there are limited data on the effect of dose increases from 400 mg/day to 600 mg/day in patients whose disease progresses at the lower dose.

3.4 Imatinib costs £12.98 per 100 mg (excluding VAT; British National Formulary 47, March 2004). The approximate annual acquisition cost of imatinib is between £19,000 (400 mg/day) and £28,500 (600 mg/day).