Bosutinib: a third generation tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia

Abstract

Bosutinib is an oral tyrosine kinase inhibitor (TKI) with very potent dual inhibitory activity against SRC and abelson gene. Bosutinib was approved in 2012 for the treatment of resistant Philadelphia chromosome positive chronic myeloid leukemia (CML). Bosutinib is a very effective TKI against all phases of intolerant or resistant CML regardless of the presence or absence of an abelson gene domain mutation, except for cases with detectable T315I or V299L. Bosutinib is overall well tolerated and associated with a unique, but manageable toxicity profile. Factors that influence the prescribing pattern of this drug are complex and include physicians’, and increasingly patients and families’ preference, patients’ comorbid conditions, schedule of administration, as well as financial factors. This paper provides an overview of CML, the TKI market, pharmacokinetics, pharmacodynamics, clinical efficacy, safety and tolerability of bosutinib.

Keywords::

• bosutinib
• chronic myeloid leukemia
• resistant
• tyrosine kinase inhibitor

Financial & competing interests disclosure

H Khoury has received honoraria from Pfizer, Ariad, Bristol-Myers-Squibb, Novartis and Teva for his participation on advisory boards. V Kota was on an advisory board meeting for Ariad and is on the speakers Bureau for Teva pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Bosutinib, approved in 2012 for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia, is an oral tyrosine kinase inhibitor with very potent dual inhibitory activity against SRC and Abelson gene.

• Bosutinib is effective against all phases of intolerant or resistant chronic myeloid leukemia regardless of the presence or absence of an Abelson gene-domain mutation, except for cases with detectable T315I or V299L.

• Diarrhea is a distinct side effect associated with bosutinib and is of early onset, low grade (grades 1–2), manageable with anti-diarrheal, short-lived and resolves spontaneously.

• Bosutinib is active as a third-line agent in patients who failed imatinib followed by dasatinib or nilotinib.