Efficacy of Bosutinib in Imatinib-Resistant Vs Dasatinib/Nilotinib-Resistant Chronic Phase Chronic Myeloid Leukemia: Results from the Phase 4 BYOND Study

Context Bosutinib is approved for patients with Philadelphia chromosome (Ph)+ chronic myeloid leukemia (CML) resistant/intolerant to prior therapy and newly diagnosed patients in chronic phase (CP). Objective To evaluate the efficacy of bosutinib in patients with Ph+ CP CML according to subgroups of resistance (imatinib vs. dasatinib/nilotinib) or intolerance to prior tyrosine kinase inhibitors (TKIs). Design BYOND ( NCT02228382 ) is an ongoing, phase 4, single-arm, open-label study. Data are reported at ≥1 year after last enrolled patient; 85% of patients had a minimum follow-up of 2 years. Setting Multicenter study in Europe and North America. Patients Patients with CML resistant/intolerant to prior TKIs. Interventions Bosutinib 500 mg QD (starting dose). Main outcome measures Cumulative response rates. Results Of 156 patients with Ph+ CP CML who received bosutinib, 52 had resistance only to imatinib, 31 had resistance to dasatinib and/or nilotinib, and 73 were intolerant to all prior TKIs. Corresponding median treatment duration was 24.1, 8.9, and 25.3 months, and median dose intensity was 360, 431, and 292 mg/day. At the data cut-off, 69.2%, 41.9%, and 53.4% of imatinib-resistant, dasatinib/nilotinib-resistant, and TKI-intolerant patients, respectively, were still receiving treatment. The main reason for discontinuation was adverse events: 19.2%, 25.8%, and 28.8% of imatinib-resistant, dasatinib/nilotinib-resistant, and TKI-intolerant patients, respectively. Corresponding discontinuations due to insufficient response occurred in 3.8%, 16.1%, and 1.4% of patients. No patient experienced on-treatment transformation to advanced phase CML. In patients without baseline complete cytogenetic response (CCyR), CCyR rates by 1 year were 65.0%, 50.0%, and 72.2% in imatinib-resistant, dasatinib/nilotinib-resistant, and TKI-intolerant patients, respectively. In patients without baseline major molecular response (MMR), cumulative MMR rates by 1 year were 55.6%, 28.6%, and 80.6% in imatinib-resistant, dasatinib/nilotinib-resistant, and TKI-intolerant patients, respectively. Deaths occurred in 3, 3, and 4 imatinib-resistant, dasatinib/nilotinib-resistant, and TKI-intolerant patients, respectively. Conclusions Response rates were similar between imatinib-resistant and TKI-intolerant patients. Despite the fact that dasatinib/nilotinib-resistant patients were more heavily pretreated and had a shorter treatment duration, responses were also seen in patients with resistance to these second-generation TKIs. These results further support bosutinib use for patients with Ph+ CP CML and resistance/intolerance to prior TKIs. Study Sponsor Pfizer.