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Safety profile of bosutinib in Japanese versus non-Japanese patients with chronic myeloid leukemia: a pooled analysis

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Abstract

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.

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Data availability

Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.

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Acknowledgements

The study was sponsored by Pfizer. The authors would like to thank Yuichiro Koide, PhD, Japan Clinical Leader in Pfizer R&D Japan, for his contributions to study conception and design and interpretation of data; and Taku Uryu and Hiroko Godai, Statistical Programming Leads in Pfizer R&D Japan, for their contributions to data analysis. Medical writing support was provided by Emily Balevich, PhD, of Engage Scientific Solutions and was funded by Pfizer.

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Correspondence to Naoto Takahashi.

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Naoto Takahashi reports research funding from Novartis, Otsuka, Pfizer, Asahi Kasei, Astellas Pharma, and Ono Pharmaceutical, and speakers bureau with Novartis, Otsuka, Pfizer, and Bristol Myers Squibb. Jorge E. Cortes reports consultancy with Amphivena Therapeutics, Astellas Pharma, Bio-Path Holdings Inc, BiolineRx, Bristol Myers Squibb, Daiichi Sankyo, Jazz Pharmaceuticals, Novartis, Pfizer, and Takeda, and research funding from Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo, Immunogen, Jazz Pharmaceuticals, Merus, Novartis, Pfizer, Sun Pharma, Takeda, Tolero Pharmaceuticals, and Trovagene. Emiko Sakaida reports research funding from Bristol Myers Squibb, Chugai, Kyowa Kirin, Ono, and Pfizer. Kenichi Ishizawa reports research funding from Novartis, AbbVie, Bayer, SymBio, Otsuka, Pfizer, Takeda, and Kyowa Kirin, and speakers bureau with Takeda, Celgene, Ono, Novartis, Chugai, and Eisai. Takaaki Ono reports honoraria from Bristol Myers Squibb, Celgene, Merck Sharp & Dohme, Novartis, Ono, Otsuka, Pfizer, and Takeda, and research funding from Celgene, Chugai, Kyowa Hakko Kirin, Merck Sharp & Dohme, Ono, and Pfizer. Itaru Matsumura reports speakers bureau with Amgen Astellas BioPharma K.K., Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo, Janssen Pharmaceutical K.K., Novartis Pharma K.K., Otsuka Pharmaceutical, Pfizer Japan Inc, and research funding from AbbVie G.K., Asahi Kasei Pharma, Chugai Pharmaceutical, Eisai, Japan Blood Products Organization, Kyowa Kirin, Mitsubishi Tanabe Pharma, MSD K.K., Nippon Shinyaku, Ono Pharmaceutical, Shionogi, Sumitomo Dainippon Pharma, Taiho Pharmaceutical, and Takeda.. Valentín García-Gutiérrez reports consultancy with Bristol Myers Squibb, Incyte, Novartis, and Pfizer, and research funding from Pfizer. Gianantonio Rosti reports research funding from Pfizer, and speakers bureau with Bristol Myers Squibb, Incyte, Novartis, and Pfizer. Chiho Ono reports employment by and stock options with Pfizer. Masayuki Ohkura and Yusuke Tanetsugu report employment by Pfizer R&D Japan G.K. Andrea Viqueira reports employment by and stock ownership in Pfizer. Tim H. Brümmendorf reports consultancy with Janssen, Merck, Novartis, and Pfizer, research funding from Novartis and Pfizer, and honoraria from Novartis and Pfizer.

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Takahashi, N., Cortes, J.E., Sakaida, E. et al. Safety profile of bosutinib in Japanese versus non-Japanese patients with chronic myeloid leukemia: a pooled analysis. Int J Hematol 115, 838–851 (2022). https://doi.org/10.1007/s12185-022-03314-y

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