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

Authors: Rogers G, Hoyle M, Thompson Coon J, Moxham T, Liu Z, Pitt M, Stein K

Journal: Health Technology Assessment Volume: 16 Issue: 22

Publication date: May 2012

DOI: 10.3310/hta16220

Citation:

Rogers G, Hoyle M, Thompson Coon J, Moxham T, Liu Z, Pitt M, et al.Dasatinib and nilotinib for imatinib-resistant or -intolerant chronic myeloid Leukaemia: A systematic review and economic evaluation. Health Technol Assess 2012;16(22)


Download: Citation (for this publication as a .ris file) (4.4 KB)


Journal issues* can be purchased by completing the form.


The cost of reports varies according to number of pages and postage address. The minimum cost for a copy sent to a UK address is £30.00. We will contact you on receipt of your completed form to advise you of actual cost. If you have any queries, please contact nihredit@southampton.ac.uk.


*We regret that unfortunately we are unable to supply bound print copies of Health Technology Assessment published before issue 12:31. However, PDFs are available to print from the "Downloads" tab of the issue page.

Responses

No responses have been published. If you would like to submit a response to this publication, please do so using the form below.

Comments submitted to the NIHR Journals Library are electronic letters to the editor. They enable our readers to debate issues raised in research reports published in the Journals Library. We aim to post within 2 working days all responses that contribute substantially to the topic investigated, as determined by the Editors.

Your name and affiliations will be published with your comment.

Once published, you will not have the right to remove or edit your response. The Editors may add, remove, or edit comments at their absolute discretion.

Post your response

Surname

Forename

Middle Initial

Occupation / Job title

Affiliation / Employer

Email

Address

Other authors

For example, if you are responding as a team or group. Please ensure you include full names and separate these using commas

Statement of competing interests

We believe that readers should be aware of any competing interests (conflicts of interest).

The International Committee of Medical Journal Editors (ICMJE) define competing interests as including: financial relationships with industry (for example through employment, consultancies, stock, ownership, honoraria, and expert testimony), either directly or through immediate family; personal relationships; academic competition; and intellectual passion.

If yes, provide details below:

Enter response title

Enter response message

Enter CAPTCHA

Security key

Regenerate security key

By submitting your response, you are stating that you agree to the terms & conditions

The full text of this issue is available as a PDF document from the Downloads section on this page.

Abstract

Background

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.

Objectives

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.

Results

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-effectiveness, it was extremely difficult to reach any conclusions regarding either agent in the ImR population. All three models (Novartis, PenTAG and Bristol-Myers Squibb) were seriously flawed in one way or another, as a consequence of the paucity of data appropriate to construct robust decision-analytic models. Accelerated and blast crisis: all available data originated from observational single-arm studies and there were considerable and potentially important differences in baseline characteristics which seriously undermined any process for making meaningful comparisons between treatments. Owing to a lack of available clinical data, de novo models of accelerated phase and blast crisis have not been developed. The economic evaluations carried out by the manufacturers of nilotinib and dasatinib were seriously undermined by the absence of evidence on high-dose imatinib in these populations.

Limitations

The study has been necessarily constrained by the paucity of available clinical data, the differences in definitions used in the studies and the subsequent impossibility of undertaking a meaningful cost-effectiveness analyses to inform all policy questions.

Conclusions

Dasatinib and nilotinib appeared efficacious in terms of obtaining cytogenetic and haematological responses in both ImR and ImI populations. It was difficult to reach any cost-effectiveness conclusions as a consequence of the paucity of the data. Future research should include a three-way, double-blind, randomised clinical trial of dasatinib, nilotinib and high-dose imatinib.

Publication updates

If you would like to receive information on publications and the latest news, click below to sign up.