TY - JOUR
T1 - Safety profile of bosutinib in Japanese versus non-Japanese patients with chronic myeloid leukemia
T2 - a pooled analysis
AU - Takahashi, Naoto
AU - Cortes, Jorge E.
AU - Sakaida, Emiko
AU - Ishizawa, Kenichi
AU - Ono, Takaaki
AU - Doki, Noriko
AU - Matsumura, Itaru
AU - García-Gutiérrez, Valentín
AU - Rosti, Gianantonio
AU - Ono, Chiho
AU - Ohkura, Masayuki
AU - Tanetsugu, Yusuke
AU - Viqueira, Andrea
AU - Brümmendorf, Tim H.
N1 - Publisher Copyright:
© 2022, Japanese Society of Hematology.
PY - 2022/6
Y1 - 2022/6
N2 - Bosutinib has been investigated in multiple clinical trials globally, including Japan, for treatment of chronic myeloid leukemia (CML). A pooled analysis of seven Pfizer-sponsored clinical trials evaluated the safety of bosutinib in Japanese (n = 138) vs non-Japanese (n = 1210) patients with CML. First-line bosutinib was administered in 54.3% vs 41.4% of patients, and second-line or later bosutinib in the remainder. Median treatment duration was 1.4 vs 2.3 years, and median relative dose intensity 78.1% vs 90.0%. Any-grade treatment-emergent adverse events (TEAEs) occurred in 100.0% vs 98.9% (grade ≥ 3: 81.9% vs 75.2%). In both groups, the most common TEAEs relevant to bosutinib were gastrointestinal (92.8% vs 84.7%), liver function (72.5% vs 34.8%), rash (63.8% vs 37.4%), and myelosuppression (55.1% vs 50.7%). TEAEs led to dose reduction in 65.2% vs 50.6%, dose interruption in 78.3% vs 68.8%, and permanent treatment discontinuation in 30.4% vs 25.4% of patients. The safety profile of bosutinib in Japanese patients was generally consistent with that in non-Japanese patients, despite a higher incidence of gastrointestinal, liver function, and rash events. TEAEs were largely manageable with dose modifications and supportive care in both groups. These data may help optimize TEAE management and outcomes in Japanese patients receiving bosutinib for CML. Trial registration ClinicalTrials.gov: NCT02130557, NCT03128411, NCT00574873, NCT00261846, NCT01903733, NCT00811070, NCT02228382.
AB - Bosutinib has been investigated in multiple clinical trials globally, including Japan, for treatment of chronic myeloid leukemia (CML). A pooled analysis of seven Pfizer-sponsored clinical trials evaluated the safety of bosutinib in Japanese (n = 138) vs non-Japanese (n = 1210) patients with CML. First-line bosutinib was administered in 54.3% vs 41.4% of patients, and second-line or later bosutinib in the remainder. Median treatment duration was 1.4 vs 2.3 years, and median relative dose intensity 78.1% vs 90.0%. Any-grade treatment-emergent adverse events (TEAEs) occurred in 100.0% vs 98.9% (grade ≥ 3: 81.9% vs 75.2%). In both groups, the most common TEAEs relevant to bosutinib were gastrointestinal (92.8% vs 84.7%), liver function (72.5% vs 34.8%), rash (63.8% vs 37.4%), and myelosuppression (55.1% vs 50.7%). TEAEs led to dose reduction in 65.2% vs 50.6%, dose interruption in 78.3% vs 68.8%, and permanent treatment discontinuation in 30.4% vs 25.4% of patients. The safety profile of bosutinib in Japanese patients was generally consistent with that in non-Japanese patients, despite a higher incidence of gastrointestinal, liver function, and rash events. TEAEs were largely manageable with dose modifications and supportive care in both groups. These data may help optimize TEAE management and outcomes in Japanese patients receiving bosutinib for CML. Trial registration ClinicalTrials.gov: NCT02130557, NCT03128411, NCT00574873, NCT00261846, NCT01903733, NCT00811070, NCT02228382.
KW - Bosutinib
KW - Chronic myeloid leukemia
KW - Japan
KW - Safety
KW - Tyrosine kinase inhibitor
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U2 - 10.1007/s12185-022-03314-y
DO - 10.1007/s12185-022-03314-y
M3 - Article
C2 - 35235189
AN - SCOPUS:85125669912
SN - 0925-5710
VL - 115
SP - 838
EP - 851
JO - International Journal of Hematology
JF - International Journal of Hematology
IS - 6
ER -