Bosutinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: results from the BELA trial

Abstract

Purpose: Bosutinib is an oral Src/Abl tyrosine kinase inhibitor. The phase III Bosutinib Efficacy and Safety in Newly Diagnosed Chronic Myeloid Leukemia (BELA) trial compared bosutinib with imatinib in newly diagnosed, chronic-phase chronic myeloid leukemia (CML).

Patients and methods: A total of 502 patients were randomly assigned 1:1 to bosutinib 500 mg per day or imatinib 400 mg per day.

Results: The complete cytogenetic response (CCyR) rate at 12 months was not different for bosutinib (70%; 95% CI, 64% to 76%) versus imatinib (68%; 95% CI, 62% to 74%; two-sided P = .601); therefore, the study did not achieve its primary end point. The major molecular response (MMR) rate at 12 months was higher with bosutinib (41%; 95% CI, 35% to 47%) compared with imatinib (27%; 95% CI, 22% to 33%; two-sided P < .001). Time to CCyR and MMR was faster with bosutinib compared with imatinib (two-sided P < .001 for both). On-treatment transformation to accelerated/blast phase occurred in four patients (2%) on bosutinib compared with 10 patients (4%) on imatinib. A total of three CML-related deaths occurred on the bosutinib arm compared with eight on the imatinib arm. The safety profiles of bosutinib and imatinib were distinct; GI and liver-related events were more frequent with bosutinib, whereas neutropenia, musculoskeletal disorders, and edema were more frequent with imatinib.

Conclusion: This ongoing trial did not meet its primary end point of CCyR at 12 months, despite the observed higher MMR rate at 12 months, faster times to CCyR and MMR, fewer on-treatment transformations to accelerated/blast phase, and fewer CML-related deaths with bosutinib compared with imatinib. Each drug had a distinct safety profile.

Trial registration: ClinicalTrials.gov NCT00574873.

Fig 1.

Disposition of patients. (*) Categories were calculated in sequential order to make the groups mutually exclusive. (†) Fifteen patients in the bosutinib arm had no postbaseline assessment because of adverse events, including elevated liver function tests (n = 5); vomiting (n = 3); anaphylactic shock (n = 2); and dissociative disorder, dyspepsia, elevated lipase, decreased platelet count, and rash (n = 1 each).

Fig 2.

Rates of (A) complete cytogenetic response and (B) major molecular response in the intent-to-treat population. Cytogenetic analysis determined the presence of Philadelphia chromosome in bone marrow aspirate and included fluorescence in situ hybridization imputation; at least 20 metaphases were required. Molecular analysis determined the number of Bcr-Abl transcripts in peripheral blood. Patients who were not evaluable were counted as nonresponders. (*) Indicates a 2-sided P < .001. (†) Indicates a 2-sided P < .05. P values were based on the Cochran-Mantel-Haenszel test and stratified by site-entered Sokal score and geographic region; P values at all time points were considered exploratory, with the exception of month 12.

Fig 3.

Rates of disease progression while on study treatment in the intent-to-treat population. (*) Includes transformation to accelerated phase (AP)/blast phase (BP) chronic myeloid leukemia (CML).