Major molecular response during the first year of dasatinib, imatinib or nilotinib treatment for newly diagnosed chronic myeloid leukemia: a network meta-analysis.

Abstract

OBJECTIVE:

No randomized trials have directly compared dasatinib with nilotinib for the treatment of newly diagnosed chronic myeloid leukemia in the chronic phase. The objective of this study was to indirectly compare these therapies using evidence from randomized trials versus imatinib, the current standard of care.

METHODS:

Randomized trials that included either dasatinib or nilotinib as first-line treatment for chronic myeloid leukemia were identified in a systematic review. Inclusion and exclusion criteria, baseline characteristics and endpoint definitions were compared across trials. The outcome of interest was major molecular response by or at 12 months. A network meta-analysis was conducted to compare rates of major molecular response among therapies while adjusting for measurement of response by or at 12 months.

RESULTS:

One trial of nilotinib versus imatinib (ENESTnd) and two trials of dasatinib versus imatinib (DASISION and the S0325 Intergroup Trial) were identified. Major molecular response was reported by and at 12 months in ENESTnd, by 12 months in DASISION, and at 12 months in the S0325 Intergroup Trial. In the network meta-analysis, nilotinib had a 97% chance of having the highest rate of major molecular response compared to dasatinib and imatinib, corresponding to absolute rates of major molecular response by month 12 of 55.2%, 44.8% and 26.7%, respectively.

CONCLUSIONS:

In this network meta-analysis, nilotinib was associated with the highest rate of major molecular response, compared to dasatinib and imatinib, during the first year of treatment in patients with newly diagnosed chronic myeloid leukemia in the chronic phase.

• Authors: James Signorovitch, Rajeev Ayyagari, William M Reichmann, Eric Q Wu, Lei Chen
• Journal: Cancer treatment reviews (Cancer Treat Rev) Vol. 40 Issue 2 Pg. 285-92 (Mar 2014) ISSN: 1532-1967 [Electronic] Netherlands
• PMID: 24112812 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Review, Systematic Review)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Benzamides
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• Thiazoles
• Imatinib Mesylate
• Protein-Tyrosine Kinases
• nilotinib
• Dasatinib

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Benzamides (therapeutic use)
• Dasatinib
• Humans
• Imatinib Mesylate
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (diagnosis, drug therapy, metabolism)
• Molecular Targeted Therapy (methods)
• Piperazines (therapeutic use)
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Protein-Tyrosine Kinases (antagonists & inhibitors)
• Pyrimidines (therapeutic use)
• Thiazoles (therapeutic use)
• Treatment Outcome