CML-413 Efficacy and Safety of Bosutinib Versus Imatinib in US Patients With Newly Diagnosed Chronic Myeloid Leukemia After 5-Years Follow-Up in the BFORE Trial

Context: Bosutinib is approved for the treatment of newly diagnosed Philadelphia chromosome-positive chronic phase (CP) chronic myeloid leukemia (CML). Objective: The efficacy and safety of bosutinib versus imatinib in US patients enrolled in BFORE was characterized. Design: BFORE (NCT02130557) was an open-label, randomized, phase 3 study. Efficacy was assessed in the intent-to-treat population (all randomized patients); safety was assessed in the safety population (patients who received ≥1 dose of study treatment). This analysis is based on the final database lock: June 12, 2020, after 5-years (240 weeks) follow-up. Setting: Global multicenter study. Patients: 536 patients with newly diagnosed CP-CML (N=88 in the US subpopulation; bosutinib [n=39] or imatinib [n=49]). Interventions: Bosutinib or imatinib 400 mg once daily (QD) starting dose. Main Outcome Measures: Major molecular response (MMR) rate and treatment-emergent adverse events (TEAEs). Results: Median (range) duration of treatment with bosutinib and imatinib was 54.8 (0.9–58.9) months and 54.8 (1.2–56.4) months, respectively. Median (range) dose intensity with bosutinib and imatinib was 383.5 (162–562) mg/day and 400.0 (189–754) mg/day, respectively. Baseline characteristics were well balanced between treatment arms. MMR at 12 months was 41.0% vs 32.7% for bosutinib vs imatinib. Cumulative MMR by 60 months was 74.4% vs 63.3% with bosutinib vs imatinib. All patients in both arms experienced at least one TEAE. The most common (≥30%) TEAEs with bosutinib were diarrhea (84.6%), nausea (61.5%), fatigue (53.8%), thrombocytopenia (41.0%), headache (35.9%), rash (33.3%), increased alanine aminotransferase (ALT; 30.8%), and constipation (30.8%); and with imatinib were nausea (63.3%), diarrhea (55.1%), fatigue (36.7%), periorbital edema (34.7%), and muscle spasm (30.6%). In the bosutinib versus imatinib treatment arm, 13 (33.3%) vs 7 (14.3%) patients permanently discontinued treatment due to AEs; the most common reasons for permanent treatment discontinuation were increased ALT (7.7%) with bosutinib, and increased lipase (4.1%) with imatinib. Conclusions: Efficacy and safety outcomes in this US subpopulation from BFORE were generally consistent with the overall study population at 5 years (Cortes et al., J Clin Oncol 2018). These results confirm the use of bosutinib as a standard of care in patients with newly diagnosed CP-CML.