Editor’s note: This article was updated to remove the final line questioning the study authors’ conclusions.
Bosutinib shows superior cytogenetic and molecular responses to imatinib in patients with newly diagnosed chronic myeloid leukemia (CML), according to initial results of a study published in the Journal of Clinical Oncology.1
Imatinib, the first approved tyrosine kinase inhibitor (TKI), has improved the life expectancy of patients with CML nearly to that of the average adult. Bosutinib, a second-generation TKI, has shown clinical activity in inhibiting expression of BCR-ABL1, the fusion gene often found in CML, even in imatinib-resistant patients.
For the ongoing phase 3 BFORE trial (ClinicalTrials.gov Identifier: NCT02130557), researchers are evaluating the safety and efficacy of bosutinib vs imatinib among patients with chronic phase CML. The primary endpoint is the major molecular response rate (MMR) at 12 months. All patients have newly diagnosed disease and have not received prior TKI therapy.
Of 536 patients enrolled, 268 were randomly assigned to receive bosutinib 400 mg daily or imatinib; only BCR-ABL1-positive patients were included in the efficacy results — 246 and 241 patients in the bosutinib and imatinib groups, respectively. Patient characteristics were similar between the groups.
The safety analysis, which included 268 patients in the bosutinib group and 265 in the imatinib group, showed a treatment discontinuation rate of 22% vs 26.8%, respectively. Thirty-four bosutinib discontinuations and 23 imatinib discontinuations were due to treatment-related adverse events; 5 bosutinib and 16 imatinib discontinuations were, however, due to suboptimal drug response or treatment failure.
The 12-month MMR rate was higher with bosutinib (47.2%) vs imatinib (36.9%; P = .02), as was the 12-month complete cytogenetic response rate (77.2% vs 66.4%, respectively; P = .0075). Responses were also noted earlier with bosutinib.
All-grade adverse events (AEs) were reported among 98.1% of bosutinib-treated and 97% of imatinib-treated patients. Grade 3 or worse events were, however, more common in the bosutinib group (56.3%) than in the imatinib group (42.6%). The most common grade 3 or worse events with bosutinib were gastrointestinal AEs (including diarrhea, nausea, vomiting, and abdominal pain; 10.8% of patients vs 3.4% with imatinib), thrombocytopenia (13.8% vs 5.7% with imatinib), and liver function–related AEs (24.3% vs 4.2% with imatinib).
Grade 3 or worse neutropenia and infection were, however, more common with imatinib (12.1% and 4.9%, respectively) than with bosutinib (6.7% and 3.4%, respectively).
The authors concluded that “bosutinib…provides benefit over imatinib, with higher rates of cytogenetic and molecular responses, and that these responses occur earlier. Bosutinib is associated with a favorable toxicity profile, with most AEs being low-grade, manageable, and improving over time.”
- Cortes JE, Gambacorti-Passerini C, Deininger MW, et al. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial. J Clin Oncol. 2017 Nov 1. doi: 10.1200/JCO.2017.74.7162 [Epub ahead of print]