TY - JOUR
T1 - Safety of bosutinib versus imatinib in the phase 3 BELA trial in newly diagnosed chronic phase chronic myeloid leukemia
AU - Gambacorti-Passerini, Carlo
AU - Cortes, Jorge E.
AU - Lipton, Jeff H.
AU - Dmoszynska, Anna
AU - Wong, Raymond S.
AU - Rossiev, Victor
AU - Pavlov, Dmitri
AU - Gogat Marchant, Karin
AU - Duvillié, Ladan
AU - Khattry, Navin
AU - Kantarjian, Hagop M.
AU - Brümmendorf, Tim H.
N1 - Publisher Copyright:
© 2014 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - 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.
AB - 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.
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U2 - 10.1002/ajh.23788
DO - 10.1002/ajh.23788
M3 - Article
C2 - 24944159
AN - SCOPUS:84908028775
SN - 0361-8609
VL - 89
SP - 947
EP - 953
JO - American Journal of Hematology
JF - American Journal of Hematology
IS - 10
ER -