Efficacy and safety of bosutinib in patients treated with prior imatinib and/or dasatinib and/or nilotinib: Subgroup analyses from the phase 4 BYOND study.

The BYOND study evaluated the efficacy and safety of bosutinib 500 mg once daily in patients with chronic myeloid leukemia (CML) resistant/intolerant to prior tyrosine kinase inhibitors (TKIs). These post-hoc analyses assessed the efficacy and safety of bosutinib by resistance or intolerance to prior TKIs (imatinib-resistant vs dasatinib/nilotinib-resistant vs TKI-intolerant), and cross-intolerance between bosutinib and prior TKIs (imatinib, dasatinib, nilotinib), in patients with Philadelphia chromosome-positive chronic phase CML. Data are reported after ≥3 years' follow-up. Of 156 patients with Philadelphia chromosome-positive chronic phase CML, 53 were imatinib-resistant, 29 dasatinib/nilotinib-resistant, and 74 intolerant to all prior TKIs; cumulative complete cytogenetic response rates at any time were 83.7%, 61.5%, and 86.8%, and cumulative major molecular response rates at any time were 72.9%, 40.7%, and 82.4%, respectively. Of 141, 95, and 79 patients who received prior imatinib, dasatinib, and nilotinib, 64 (45.4%), 71 (74.7%), and 60 (75.9%) discontinued the respective TKI due to intolerance; of these, 2 (3.1%), 5 (7.0%), and 0 had cross-intolerance with bosutinib. The response rates observed in TKI-resistant and TKI-intolerant patients, and low cross-intolerance between bosutinib and prior TKIs, further support bosutinib use for patients with Philadelphia chromosome-positive chronic phase CML resistant/intolerant to prior TKIs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02228382.

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Déclaration de conflit d'intérêts

Declaration of Competing Interest B. Douglas Smith: honoraria for consulting to Agios, Celgene, Jazz Pharmaceuticals, Novartis and Pfizer, and received research support from Pfizer. Tim H. Brümmendorf: consultant for Janssen, Merck, Novartis, Pfizer, and Takeda, and received research support from Novartis and Pfizer. Gail J. Roboz: consultancy, advisory board or data and safety monitoring committee for AbbVie, Actinium, Agios, Amphivena, Argenx, Array Biopharma, Astex, Astellas, AstraZeneca, Bayer, Celgene, Celltrion, Daiichi Sankyo, Eisai, Epizyme, Helsinn, Janssen, Jasper Therapeutics, Jazz, MEI Pharma – IDMC Chair, Novartis, Orsenix, Otsuka, Pfizer, Roche/Genentech, Sandoz, Takeda – IRC Chair, Trovagene. Received research support from Cellectis and Pfizer. Carlo Gambacorti-Passerini: provides consultancy to Bristol-Myers Squibb and received honoraria and research support from Pfizer. Aude Charbonnier: provides consultancy to Novartis and Pfizer; speaker’s bureau for Incyte; received research support from Pfizer. Andrea Viqueira, Eric Leip, Simon Purcell, and Erinn Goldman: employees of and have stock/stock options in Pfizer. Francis Giles: consultant to Actuate Therapeutics Inc, provides expert testimony to Novartis, and received research support from Pfizer. Thomas Ernst and Andreas Hochhaus: received research support from Bristol-Myers Squibb, Incyte, Novartis, and Pfizer. Gianantonio Rosti: received research support from Pfizer and served on the speaker bureau for Bristol-Myers Squibb, Incyte, Novartis, and Pfizer.