Bosutinib in previously treated CML and in first-line comparison with imatinib

Abstract

Bosutinib was recently approved for the treatment of chronic phase (CP), accelerated phase (AP), or blast phase (BP) Philadelphia chromosomepositive (Ph ) chronic myeloid leukemia (CML) in adult patients with resistance or intolerance to prior therapy. The approval was based on findings in a combined phase 1/2 single-arm trial. The recently reported phase 3 BELA trial compared bosutinib and imatinib as first-line treatments in patients with CP CML and reported no difference in complete cytogenetic response (CCyR) rates at 1 year, but improved major molecular response (MMR) rate and time to response, as well as a distinct safety profile. Bosutinib is an oral dual SRC/ABL kinase inhibitor that is active against many BCR-ABL mutations associated with imatinib resistance (with the exception of T315I and V299L) and that has reduced activity against nonspecific molecular targets (eg, c-KIT and plateletderived growth factor receptor) associated with toxicities reported for other second-generation tyrosine kinase inhibitors (TKIs). CML is characterized by a constitutively active BCR-ABL fusion protein, and SRC-family kinases have a critical role in cell adhesion, invasion, proliferation, survival, and angiogenesis. Bosutinib has been found to inhibit growth of experimental tumors that express several imatinib-resistant forms of BCR-ABL.