Bosutinib is approved in the United States, Europe, Japan, and other countries for treatment of newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML), and CML resistant/intolerant to prior therapy. In the phase 3 BFORE trial (Clinicaltrials.gov, NCT02130557), patients were randomized 1:1 to first-line bosutinib or imatinib 400 mg once daily. We examined efficacy, safety, and patient-reported outcomes of bosutinib vs imatinib and pharmacokinetics of bosutinib in the Asian (n = 33 vs 34) and non-Asian (n = 235 vs 234) subpopulations of BFORE followed for at least 24 months. At the data cutoff date, 72.7 vs 66.7% of Asian and 70.6 vs 66.4% of non-Asian patients remained on treatment. The major molecular response rate at 24 months favored bosutinib vs imatinib among Asian (63.6 vs 38.2%) and non-Asian (60.9 vs 52.6%) patients, as did the complete cytogenetic response rate by 24 months (86.7 vs 76.7%, 81.5 vs 76.3%). Treatment-emergent adverse events in both subpopulations were consistent with the primary BFORE results. Trough bosutinib concentration levels tended to be higher in Asian patients. Health-related quality of life was maintained after 12 months of bosutinib in both subpopulations. These results support bosutinib as a first-line treatment option in Asian patients with CP CML.
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Pfizer Inc. BOSULIF® (bosutinib) prescribing information. New York: Pfizer Inc; 2017.
European Medicines Agency. BOSULIF® (bosutinib) summary of product characteristics. London: European Medicines Agency; 2018.
Pfizer Japan Inc. BOSULIF® (bosutinib hydrate) prescribing information. Tokyo: Pfizer Japan Inc; 2020.
Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim DW, et al. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial. J Clin Oncol. 2018;36:231–7.
Cortes JE, Kantarjian HM, Brümmendorf TH, Kim DW, Turkina AG, Shen ZX, et al. Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome-positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood. 2011;118:4567–76.
Cortes JE, Khoury HJ, Kantarjian HM, Lipton JH, Kim DW, Schafhausen P, et al. Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib. Am J Hematol. 2016;91:1206–14.
Cortes JE, Mauro MJ, Deininger MWN, Chuah C, Kim D-W, Kota V, et al. Bosutinib vs imatinib for newly diagnosed chronic myeloid leukemia in the BFORE trial: 24-month follow-up. J Clin Oncol. 2018;36:7002.
Kim DW, Goh YT, Hsiao HH, Caguioa PB, Kim D, Kim WS, et al. Clinical profile of dasatinib in Asian and non-Asian patients with chronic myeloid leukemia. Int J Hematol. 2009;89:664–72.
Mendizabal AM, Younes N, Levine PH. Geographic and income variations in age at diagnosis and incidence of chronic myeloid leukemia. Int J Hematol. 2016;103:70–8.
Ng KP, Hillmer AM, Chuah CT, Juan WC, Ko TK, Teo AS, et al. A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer. Nat Med. 2012;18:521–8.
Than H, Lye WK, Sng C, Allen JC Jr, Ong ST, Chuah C. BIM deletion polymorphism profiling complements prognostic values of risk scores in imatinib-treated Asian chronic myeloid leukemia patients. Leuk Lymphoma. 2019;60:234–7.
Green H, Skoglund K, Rommel F, Mirghani RA, Lotfi K. CYP3A activity influences imatinib response in patients with chronic myeloid leukemia: a pilot study on in vivo CYP3A activity. Eur J Clin Pharmacol. 2010;66:383–6.
Abbas R, Hsyu PH. Clinical pharmacokinetics and pharmacodynamics of bosutinib. Clin Pharmacokinet. 2016;55:1191–204.
Zhou Q, Yu X, Shu C, Cai Y, Gong W, Wang X, et al. Analysis of CYP3A4 genetic polymorphisms in Han Chinese. J Hum Genet. 2011;56:415–22.
Hino M, Matsumura I, Fujisawa S, Ishizawa K, Ono T, Sakaida E, et al. Phase 2 study of bosutinib in Japanese patients with newly diagnosed chronic phase chronic myeloid leukemia. Int J Hematol. 2020;112:24–32.
Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122:872–84.
Cella D, Jensen SE, Webster K, Hongyan D, Lai JS, Rosen S, et al. Measuring health-related quality of life in leukemia: the functional assessment of cancer therapy-leukemia (FACT-Leu) questionnaire. Value Health. 2012;15:1051–8.
EuroQol Group. EuroQol–a new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199–208.
Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim DW, et al. Patient-reported outcomes in the phase 3 BFORE trial of bosutinib versus imatinib for newly diagnosed chronic phase chronic myeloid leukemia. J Cancer Res Clin Oncol. 2019;145:1589–99.
Trask PC, Cella D, Besson N, Kelly V, Masszi T, Kim DW. Health-related quality of life of bosutinib (SKI-606) in imatinib-resistant or imatinib-intolerant chronic phase chronic myeloid leukemia. Leuk Res. 2012;36:438–42.
Chuah CT, Nakamae H, Shen ZX, Bradley-Garelik MB, Kim DW. Efficacy and safety of dasatinib versus imatinib in the east Asian subpopulation of the DASISION trial of newly diagnosed chronic myeloid leukemia in chronic phase. Leuk Lymphoma. 2014;55:2093–100.
Nakamae H, Fukuda T, Nakaseko C, Kanda Y, Ohmine K, Ono T, et al. Nilotinib vs. imatinib in Japanese patients with newly diagnosed chronic myeloid leukemia in chronic phase: long-term follow-up of the Japanese subgroup of the randomized ENESTnd trial. Int J Hematol. 2018;107:327–36.
Wang J, Shen ZX, Saglio G, Jin J, Huang H, Hu Y, et al. Phase 3 study of nilotinib vs imatinib in Chinese patients with newly diagnosed chronic myeloid leukemia in chronic phase: ENESTchina. Blood. 2015;125:2771–8.
Nakamae H, Shibayama H, Kurokawa M, Fukuda T, Nakaseko C, Kanda Y, et al. Nilotinib as frontline therapy for patients with newly diagnosed Ph+ chronic myeloid leukemia in chronic phase: results from the Japanese subgroup of ENESTnd. Int J Hematol. 2011;93:624–32.
Saglio G, Kim DW, Issaragrisil S, le Coutre P, Etienne G, Lobo C, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362:2251–9.
Kim D-W, Granvil C, Demirhan E, Reynolds J, Jin Y, Wang Y, et al. Comparison of steady-state imatinib (IM) trough levels, clinical response, and safety between Caucasian and Asian patients with chronic myeloid leukemia in chronic phase (CML-CP) treated with 400 mg and 800 mg daily doses of IM in the tyrosine kinase inhibitor optimization and selectivity (TOPS) study. Blood. 2009;114:1127.
Larson RA, Yin OQ, Hochhaus A, Saglio G, Clark RE, Nakamae H, et al. Population pharmacokinetic and exposure-response analysis of nilotinib in patients with newly diagnosed Ph+ chronic myeloid leukemia in chronic phase. Eur J Clin Pharmacol. 2012;68:723–33.
Kreutzman A, Yadav B, Brümmendorf TH, Gjertsen BT, Lee MH, Janssen J, et al. Immunological monitoring of newly diagnosed CML patients treated with bosutinib or imatinib first-line. Oncoimmunology. 2019;8:e1638210.
Khoury HJ, Gambacorti-Passerini C, Brümmendorf TH. Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia. Ann Oncol. 2018;29:578–87.
Nakaseko C, Takahashi N, Ishizawa K, Kobayashi Y, Ohashi K, Nakagawa Y, et al. A phase 1/2 study of bosutinib in Japanese adults with Philadelphia chromosome-positive chronic myeloid leukemia. Int J Hematol. 2015;101:154–64.
Brümmendorf TH, Cortes JE, de Souza CA, Guilhot F, Duvillie L, Pavlov D, et al. Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukaemia: results from the 24-month follow-up of the BELA trial. Br J Haematol. 2015;168:69–81.
Gambacorti-Passerini C, Cortes JE, Lipton JH, Dmoszynska A, Wong RS, Rossiev V, et al. Safety of bosutinib versus imatinib in the phase 3 BELA trial in newly diagnosed chronic phase chronic myeloid leukemia. Am J Hematol. 2014;89:947–53.
Garrett M, Knight B, Cortes JE, Deininger MW. Optimizing dose of bosutinib to minimize adverse events while maintaining efficacy in patients with newly diagnosed chronic myelogenous leukemia. Blood. 2017;130(suppl 1):2899.
Mita A, Abumiya M, Miura M, Niioka T, Takahashi S, Yoshioka T, et al. Correlation of plasma concentration and adverse effects of bosutinib: standard dose or dose-escalation regimens of bosutinib treatment for patients with chronic myeloid leukemia. Exp Hematol Oncol. 2018;7:9.
Brummendorf TH, Gambacorti-Passerini C, Bushmakin AG, Cappelleri JC, Viqueira A, Reisman A, et al. Relationship between molecular response and quality of life with bosutinib or imatinib for chronic myeloid leukemia. Ann Hematol. 2020;99:1241–9.
The authors would like to thank Dong-Wook Kim for his contributions to the provision of study materials/patients and the collection and assembly of data. This study was sponsored by Pfizer. Medical writing support was provided by Emily Balevich, PhD, of Engage Scientific Solutions and was funded by Pfizer.
Conflict of interest
Charles Chuah has received research funding from Bristol-Myers Squibb and honoraria from Bristol-Myers Squibb, Novartis, Korea Otsuka Pharmaceuticals and Chiltern International. Kiat Hoe Ong served on advisory boards for Abbvie, AstraZeneca, Johnson & Johnson, and Novartis; received speaker fees from Johnson & Johnson and Novartis; and received conference registration/travel accommodations from Amgen, Bristol-Myers Squib, and Celgene. Young Rok Do served as a consultant for Bristol-Myers Squibb, Novartis, Pfizer, Takeda, and Ilynag Pharma. Masayuki Ohkura and Chiho Ono are employees of Pfizer. Andrea Viqueira is an employee of and owns stock in Pfizer. Jorge E. Cortes has received research funding from Bristol-Myers Squibb, Novartis, Pfizer, Takeda, and Sun Pharma and served as a consultant for Bristol-Myers Squibb, Novartis, Pfizer, Takeda, and Fusion Pharma. Tim H. Brümmendorf has received research funding from Novartis and Pfizer and participated in advisory boards and/or satellite symposia for Ariad, Bristol-Myers Squibb, Janssen, Merck, Novartis, and Pfizer. Liang Piu Koh, Tontanai Numbenjapon, and Dae Young Zang declare that they have no conflicts of interest.
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Chuah, C., Koh, L.P., Numbenjapon, T. et al. Efficacy and safety of bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia in the Asian subpopulation of the phase 3 BFORE trial. Int J Hematol 114, 65–78 (2021). https://doi.org/10.1007/s12185-021-03144-4
- Chronic myeloid leukemia