Bosutinib, an orally active, Src/Abl
tyrosine kinase inhibitor, has demonstrated clinical activity and acceptable tolerability in chronic phase
chronic myeloid leukemia (CP CML). This updated analysis of the BELA trial assessed the safety profile and management of toxicities of
bosutinib versus
imatinib in adults with newly diagnosed (≤6 months) CP CML after >30 months from accrual completion. Among patients randomized to
bosutinib 500 mg/d (n = 250) or
imatinib 400 mg/d (n = 252), 248 and 251, respectively, received ≥1 dose of study treatment. Adverse events (AEs; any grade) with
bosutinib versus
imatinib were significantly more common for certain gastrointestinal events (
diarrhea, 70% vs. 26%; P < 0.001;
vomiting, 33% vs. 16%; P < 0.001),
alanine aminotransferase (33% vs. 9%; P < 0.001) and
aspartate aminotransferase (28% vs. 10%; P < 0.001) elevations, and
pyrexia (19% vs. 12%; P = 0.046). AEs significantly less common with
bosutinib included
edema (periorbital, 2% vs. 14%; P < 0.001; peripheral, 5% vs. 12%; P = 0.006), musculoskeletal (
myalgia, 5% vs. 12%; P = 0.010;
muscle cramps, 5% vs. 22%; P < 0.001; bone
pain, 4% vs. 11%; P = 0.003), increased
creatine phosphokinase (8% vs. 20%; P < 0.001),
neutropenia (13% vs. 30%; P < 0.001), and
leukopenia (9% vs. 22%; P < 0.001). Between-group differences in the incidence of cardiac and vascular AEs were not significant.
Diarrhea was typically transient, mostly Grade 1/2, occurring early during treatment, and was manageable with
antidiarrheal medication. Despite higher rates of
aminotransferase elevation with
bosutinib, events were managed in most patients with dose modification and/or concomitant medication.
Bosutinib had a manageable safety profile distinct from that of
imatinib in patients with newly diagnosed CP CML.