Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib

Am J Hematol. 2016 Dec;91(12):1206-1214. doi: 10.1002/ajh.24536. Epub 2016 Sep 15.

Abstract

Bosutinib is an Src/Abl tyrosine kinase inhibitor (TKI) indicated for adults with Ph+ chronic myeloid leukemia (CML) resistant/intolerant to prior TKIs. This long-term update of an ongoing phase 1/2 study evaluated the efficacy and safety of third-/fourth-line bosutinib in adults with chronic phase (CP) CML. Median durations of treatment and follow-up were 8.6 (range, 0.2-87.7) months and 32.7 (0.3-93.3) months, respectively. Cumulative confirmed complete hematologic response (cCHR) and major cytogenetic response (MCyR) rates were 74% (95% CI, 65-81%) and 40% (31-50%), respectively; Kaplan-Meier (K-M) probability of maintaining cCHR or MCyR at 4 years was 63% (95% CI, 50-73%) and 69% (52-81%). Cumulative incidence of on-treatment disease progression (PD)/death at 4 years was 24% (95% CI, 17-33%); K-M 4-year overall survival was 78% (68-85%). Baseline Ph+ cells ≤35 vs. ≥95% was prognostic of MCyR and CCyR by 3 and 6 months, increased baseline basophils was prognostic of PD/death, and no prior response to second-line TKI was prognostic of death. Common adverse events included diarrhea (83%), nausea (48%), vomiting (38%), and thrombocytopenia (39%). Bosutinib demonstrates durable efficacy and a toxicity profile similar to previous bosutinib studies in CP CML patients resistant/intolerant to multiple TKIs, representing an important treatment option for patients in this setting. This trial is registered at www.clinicaltrials.gov (NCT00261846). Am. J. Hematol. 91:1206-1214, 2016. © 2016 Wiley Periodicals, Inc.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aniline Compounds / adverse effects
  • Aniline Compounds / therapeutic use*
  • Antineoplastic Agents / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Dasatinib
  • Disease Progression
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / mortality
  • Longitudinal Studies
  • Middle Aged
  • Nitriles / adverse effects
  • Nitriles / therapeutic use*
  • Pyrimidines
  • Quinolines / adverse effects
  • Quinolines / therapeutic use*
  • Remission Induction
  • Salvage Therapy / methods*
  • Survival Analysis
  • Treatment Outcome
  • Young Adult

Substances

  • 4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide
  • Aniline Compounds
  • Antineoplastic Agents
  • Nitriles
  • Pyrimidines
  • Quinolines
  • bosutinib
  • Imatinib Mesylate
  • Dasatinib

Associated data

  • ClinicalTrials.gov/NCT00261846