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Eur J Cancer. 2018 Nov;104:9-20. doi: 10.1016/j.ejca.2018.08.016. Epub 2018 Oct 5.

Comparative efficacy and safety of tyrosine kinase inhibitors for chronic myeloid leukaemia: A systematic review and network meta-analysis.

Author information

1
Pharmaceutical Sciences Postgraduate Programme, Universidade Federal Do Paraná, Curitiba, Brazil. Electronic address: marianamfachi@gmail.com.
2
Pharmaceutical Sciences Postgraduate Programme, Universidade Federal Do Paraná, Curitiba, Brazil. Electronic address: stumpf.tonin@ufpr.br.
3
Pharmaceutical Sciences Postgraduate Programme, Universidade Federal Do Paraná, Curitiba, Brazil. Electronic address: leticialeonart@gmail.com.
4
Pharmaceutical Sciences Postgraduate Programme, Universidade Federal Do Paraná, Curitiba, Brazil. Electronic address: karinasilva.aguiar@gmail.com.
5
Department of Clinical Analysis, Universidade Federal Do Paraná, Curitiba, Brazil. Electronic address: luanalnz@yahoo.com.br.
6
Department of Public Health, Universidade Federal Do Paraná, Curitiba, Brazil. Electronic address: bonald@ufpr.br.
7
Research Institute for Medicines (iMed.ULisboa), Department of Social Pharmacy, Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal. Electronic address: f-llimos@ff.ul.pt.
8
Department of Pharmacy, Universidade Federal Do Paraná, Curitiba, Brazil. Electronic address: pontarolo@ufpr.br.

Abstract

BACKGROUND:

The pharmacotherapy of chronic myeloid leukaemia (CML) is mainly based on tyrosine kinase inhibitors (TKIs). The aim of this study was to compare the efficacy and safety of all TKIs in CML patients.

METHODS:

We conducted a systematic review with network meta-analysis (NMA) of randomised controlled trials (RCTs), including imatinib, nilotinib, dasatinib, bosutinib, radotinib and ponatinib. Searches were performed in PubMed, Scopus, Web of Science and SciELo (March 2018). The NMAs were built for six outcomes at 12 months: complete cytogenetic response (CCyR), major cytogenetic response (MCyR), deep molecular response, major molecular response (MMR), complete haematologic response and incidence of serious adverse events. We conducted rank order and surface under the cumulative ranking curve (SUCRA) analyses.

RESULTS:

Thirteen RCTs were included (n = 5079 patients). Statistical differences were observed for some comparisons in all outcomes. Imatinib 400 mg was considered the safest drug (SUCRA values of 10.3%) but presented low efficacy. Overall, nilotinib 600 mg was superior to the other TKI in efficacy (SUCRA values of 61.1% for CCyR, 81.0% for MMR, 90.0% for MCyR); however, no data on its safety profile at 12 months were reported.

INTERPRETATION:

Our results suggest that nilotinib should be upgraded to first-line therapy for CML, although further cost-effectiveness analyses, including the new TKI (i.e., ponatinib, radotinib), are needed.

KEYWORDS:

Chronic myeloid leukaemia; Efficacy; Network meta-analysis; Safety; Tyrosine kinase inhibitors

PMID:
30296736
DOI:
10.1016/j.ejca.2018.08.016

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