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Blood. 2012 Apr 12;119(15):3403-12. doi: 10.1182/blood-2011-11-390120. Epub 2012 Feb 27.

Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure.

Author information

1
Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA. hkhoury@emory.edu

Abstract

Bosutinib, a dual Src/Abl tyrosine kinase inhibitor (TKI), has shown potent activity against chronic myeloid leukemia (CML). This phase 1/2 study evaluated the efficacy and safety of once-daily bosutinib 500 mg in leukemia patients after resistance/intolerance to imatinib. The current analysis included 118 patients with chronic-phase CML who had been pretreated with imatinib followed by dasatinib and/or nilotinib, with a median follow-up of 28.5 months. In this subpopulation, major cytogenetic response was attained by 32% of patients; complete cytogenetic response was attained by 24%, including in one of 3 patients treated with 3 prior TKIs. Complete hematologic response was achieved/maintained in 73% of patients. On-treatment transformation to accelerated/blast phase occurred in 5 patients. At 2 years, Kaplan-Meier-estimated progression-free survival was 73% and estimated overall survival was 83%. Responses were seen across Bcr-Abl mutations, including those associated with dasatinib and nilotinib resistance, except T315I. Bosutinib had an acceptable safety profile; treatment-emergent adverse events were primarily manageable grade 1/2 gastrointestinal events and rash. Grade 3/4 nonhematologic adverse events (> 2% of patients) included diarrhea (8%) and rash (4%). Bosutinib may offer a new treatment option for patients with chronic-phase CML after treatment with multiple TKIs. This trial was registered at www.clinicaltrials.gov as NCT00261846.

PMID:
22371878
PMCID:
PMC4916559
DOI:
10.1182/blood-2011-11-390120
[Indexed for MEDLINE]
Free PMC Article

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