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J Clin Oncol. 2018 Jan 20;36(3):231-237. doi: 10.1200/JCO.2017.74.7162. Epub 2017 Nov 1.

Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial.

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Jorge E. Cortes, University of Texas MD Anderson Cancer Center, Houston, TX; Carlo Gambacorti-Passerini, University of Milano-Bicocca, Monza, Italy; Michael W. Deininger, University of Utah, Salt Lake City, UT; Michael J. Mauro, Memorial Sloan Kettering Cancer Center, New York, NY; Charles Chuah, Singapore General Hospital, Duke-National University of Singapore Medical School, Singapore, Singapore; Dong-Wook Kim, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, South Korea; Irina Dyagil, National Research Center for Radiation Medicine, Kiev; Nataliia Glushko, Ivano-Frankivsk Regional Clinical Hospital, Ivano-Frankivsk, Ukraine; Dragana Milojkovic, Imperial College London at Hammersmith Hospital London; Laurence Reilly and Allison Jeynes-Ellis, Avillion, London, United Kingdom; Philipp le Coutre, Charité-Universitätsmedizin Berlin, Berlin; Andreas Hochhaus, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena; Tim H. Brümmendorf, Universitätsklinikum RWTH Aachen, Aachen, Germany; Valentin Garcia-Gutierrez, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain; Eric Leip, Pfizer, Cambridge, MA; Nathalie Bardy-Bouxin, Pfizer International Operation, Paris, France.


Purpose Bosutinib is a potent dual SRC/ABL kinase inhibitor approved for adults with Philadelphia chromosome-positive chronic myeloid leukemia (CML) resistant and /or intolerant to prior therapy. We assessed the efficacy and safety of bosutinib versus imatinib for first-line treatment of chronic-phase CML. Methods In this ongoing, multinational, phase III study, 536 patients with newly diagnosed chronic-phase CML were randomly assigned 1:1 to receive 400 mg of bosutinib once daily (n = 268) or imatinib (n = 268). Per protocol, efficacy was assessed in patients who were Philadelphia chromosome-positive with typical (e13a2/e14a2) transcripts (bosutinib, n = 246; imatinib, n = 241). Patients with Philadelphia chromosome-negative-/ BCR-ABL1-positive status and those with unknown Philadelphia chromosome status and/or atypical BCR-ABL1 transcript type were excluded from this population. Results The major molecular response (MMR) rate at 12 months (primary end point) was significantly higher with bosutinib versus imatinib (47.2% v 36.9%, respectively; P = .02), as was complete cytogenetic response (CCyR) rate by 12 months (77.2% v 66.4%, respectively; P = .0075). Cumulative incidence was favorable with bosutinib (MMR: hazard ratio, 1.34; P = .0173; CCyR: hazard ratio, 1.38; P < .001), with earlier response times. Four patients (1.6%) receiving bosutinib and six patients (2.5%) receiving imatinib experienced disease progression to accelerated/blast phase. Among treated patients, 22.0% of patients receiving bosutinib and 26.8% of patients receiving imatinib discontinued treatment, most commonly for drug-related toxicity (12.7% and 8.7%, respectively). Grade ≥ 3 diarrhea (7.8% v 0.8%) and increased ALT (19.0% v 1.5%) and AST (9.7% v 1.9%) levels were more common with bosutinib. Cardiac and vascular toxicities were uncommon. Conclusion Patients who received bosutinib had significantly higher rates of MMR and CCyR and achieved responses faster than those who received imatinib. Consistent with the known safety profile, GI events and transaminase elevations were more common with bosutinib. Results indicate bosutinib may be an effective first-line treatment for chronic-phase CML.

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