Dasatinib (Sprycel, Bristol-Myers Squibb), a tyrosine kinase inhibitor, is an orally active inhibitor of Src and the Src family of tyrosine kinases. These are involved in cell growth, differentiation, migration and survival, and many are involved in oncogenesis, tumour metastasis and angiogenesis.
Imatinib (Glivec, Novartis Pharmaceuticals) is an orally active tyrosine kinase inhibitor, designed to competitively inhibit Bcr‑Abl tyrosine kinase activity. By blocking specific signals in cells expressing Bcr‑Abl, imatinib reduces the uncontrolled proliferation of white blood cells that is a characteristic feature of chronic myeloid leukaemia (CML).
Nilotinib (Tasigna, Novartis Pharmaceuticals), a tyrosine kinase inhibitor (TKI), is an orally active phenylaminopyrimidine derivative of imatinib. Studies suggest that nilotinib inhibits 32 of 33 mutant Bcr-Abl forms that are resistant to imatinib.
Dasatinib has a marketing authorisation for the treatment of adult patients with 'newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukaemia (CML) in the chronic phase' and adult patients with 'chronic, accelerated or blast phase CML with resistance or intolerance to prior therapy including imatinib mesilate'.
Imatinib has a marketing authorisation for the treatment of 'adult and paediatric patients with newly diagnosed Philadelphia chromosome (bcr-abl) positive (Ph+) chronic myeloid leukaemia (CML) for whom bone marrow transplantation is not considered as the first line of treatment' and for 'adult and paediatric patients with Ph+ CML in chronic phase after failure of interferon-alpha therapy or in accelerated phase or blast crisis'.
Nilotinib has a marketing authorisation for the treatment of adult patients with 'newly diagnosed Philadelphia chromosome positive chronic myeloid leukaemia (CML) in the chronic phase' and adult patients with 'chronic phase and accelerated-phase Philadelphia chromosome positive CML with resistance or intolerance to prior therapy including imatinib'.
The most common reported side effects with dasatinib are headache, pleural effusion, shortness of breath, cough, diarrhoea, nausea, vomiting, abdominal pain, skin rash, musculoskeletal pain, infections, haemorrhage, superficial oedema, fatigue, fever, neutropenia, thrombocytopenia and anaemia. The summary of product characteristics states: 'Dasatinib should be administered with caution to patients who have or may develop prolongation of the QT interval'.
The most common side effects with imatinib are nausea, vomiting, oedema (fluid retention), muscle cramps, skin rash, diarrhoea, abdominal pain, headache and fatigue.
The most common side effects with nilotinib are thrombocytopenia, neutropenia, anaemia, headache, nausea, constipation, diarrhoea, rash, pruritus, fatigue and increased blood levels of lipase and bilirubin. Nilotinib prolongs the QT interval and is therefore contraindicated in people with hypokalaemia, hypomagnesaemia or long QT syndrome.
For full details of adverse reactions and contraindications, see the summary of product characteristics of the respective technologies.
Dasatinib is administered orally. The recommended starting dosage is 100 mg once daily in the chronic phase or 140 mg once daily in the accelerated and blast-crisis phase and treatment should continue until disease progression or until no longer tolerated by the patient. Dose increase or reduction is recommended based on patient response and tolerability.
Imatinib is administered orally. The recommended starting dosage is 400 mg once daily in the chronic phase or 600 mg once daily in the accelerated and blast-crisis phase and treatment should be continued as long as the patient continues to benefit. Dose increase to 600 mg once daily in the chronic phase or 800 mg (400 mg twice daily) in the accelerated and blast-crisis phase may be considered for people who have imatinib resistance.
Nilotinib is administered orally. The recommended starting dosage is 400 mg twice daily for imatinib-resistant or intolerant CML in the chronic phase and 400 mg twice daily in the accelerated phase and treatment should be continued as long as the patient continues to benefit.
Dasatinib is available at a cost of £2,504.96 for both a pack of 30 100-mg or 140-mg tablets (excluding VAT; 'British national formulary' [BNF] online, accessed October 2016). The cost of dasatinib treatment is £30,477.00 per year, assuming a treatment regimen of 100 mg once daily or 140 mg once daily. The company has agreed a patient access scheme with the Department of Health. This scheme provides a simple discount to the list price of dasatinib, with the discount applied at the point of purchase or invoice. The level 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.
Imatinib was available at a cost of £1,604.00 for a 400-mg 30‑tablet pack (excluding VAT; BNF edition 61) resulting in an annual cost of imatinib treatment of £39,033.00, assuming a treatment regimen of 400 mg twice daily. The cost of imatinib has increased to £1,836.48 for a 400-mg 30‑tablet pack (excluding VAT; BNF online, accessed October 2016). The cost of imatinib treatment is now £44,718.00 per year assuming a treatment regimen of 400 mg twice daily. Costs may vary in different settings because of negotiated procurement discounts.
Nilotinib is available at a cost of £2,432.85 for a pack of 112 200-mg tablets (excluding VAT; BNF online, accessed October 2016). The cost of nilotinib treatment is £31,736.00 per year, assuming a treatment regimen of 400 mg twice daily. The company has agreed a patient access scheme with the Department of Health. This scheme provides a simple discount to the list price of nilotinib, with the discount applied at the point of purchase or invoice. The level 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.