Dasatinib and nilotinib for imatinib-resistant or -intolerant chronic myeloid leukaemia: a systematic review and economic evaluation

• Published in: Health technology assessment (Winchester, England) England), 2012, Vol.16 (22), p.1-410
• Main Authors: Rogers, G, Hoyle, M, Thompson Coon, J, Moxham, T, Liu, Z, Pitt, M, Stein, K
• Format: Article
• Language: English
• Subjects: Benzamides; Blast Crisis - drug therapy; chronic myeloid leukaemia; clinical effectiveness; Clinical Trials as Topic; Cost-Benefit Analysis; cost-effectiveness; Dasatinib; Decision Support Techniques; Disease Progression; Drug Resistance, Neoplasm; Health Care Costs - statistics & numerical data; Humans; Imatinib Mesylate; imatinib-intolerant; imatinib-resistant; Incidence; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myeloid, Accelerated Phase - drug therapy; Leukemia, Myeloid, Chronic-Phase - drug therapy; Models, Economic; nilotinib; Piperazines - pharmacology; Piperazines - therapeutic use; Prognosis; Protein Kinase Inhibitors - economics; Protein Kinase Inhibitors - therapeutic use; Pyrimidines - economics; Pyrimidines - pharmacology; Pyrimidines - therapeutic use; Quality of Life; systematic review; Thiazoles - economics; Thiazoles - therapeutic use
• ISSN: 1366-5278; 2046-4924
• DOI: 10.3310/hta16220

Chronic myeloid leukaemia (CML) is a form of cancer affecting the blood, characterised by excessive proliferation of white blood cells in the bone marrow and circulating blood. In the UK, an estimated 560 new cases of CML are diagnosed each year. The purpose of this study was to assess the clinical effectiveness and cost-effectiveness of dasatinib and nilotinib in the treatment of people with imatinib-resistant (ImR) and imatinib-intolerant (ImI) CML. A systematic review of the clinical effectiveness literature, a review of manufacturer submissions and a critique and exploration of manufacturer submissions for accelerated phase and blast crisis CML were carried out and a decision-analytic model was developed to estimate the cost-effectiveness of dasatinib and nilotinib in chronic phase CML. SYSTEMATIC REVIEW METHODS: Key databases were searched for relevant studies from their inception to June 2009 [MEDLINE (including MEDLINE In-Process & Other Non-Indexed Citations), EMBASE, (ISI Web of Science) Conference Proceedings Citation Index and four others]. One reviewer assessed titles and abstracts of studies identified by the search strategy, with a sample checked by a second reviewer. The full text of relevant papers was obtained and screened against the full inclusion criteria independently by two reviewers. Data from included studies were extracted by one reviewer and checked by a second. Clinical effectiveness studies were synthesised through narrative review. ECONOMIC EVALUATION METHODS: Cost-effectiveness analyses reported in manufacturer submissions to the National Institute of Health and Clinical Excellence were critically appraised and summarised narratively. In addition, the models for accelerated phase and blast crisis underwent a more detailed critique and exploration. Two separate decision-analytic models were developed for chronic phase CML, one simulating a cohort of individuals who have shown or developed resistance to normal dose imatinib and one representing individuals who have been unable to continue imatinib treatment owing to adverse events. One-way, multiway and probabilistic sensitivity analyses were performed to explore structural and parameter uncertainty. Fifteen studies were included in the systematic review. Chronic phase: effectiveness data were limited but dasatinib and nilotinib appeared efficacious in terms of obtaining cytogenetic response and haematological response in both ImR and ImI populations. In terms of cost-effectiven