Treatment with first-line bosutinib resulted in improved outcomes for patients with chronic-phase chronic myeloid leukemia (CML) compared with treatment with imatinib, according to results of the BFORE trial. Patients assigned bosutinib had a higher rate of major molecular response at 12 months, with a favorable toxicity profile. The results were published in the Journal of Clinical Oncology.
Based on these results, “bosutinib can be an important alternative for patients with previously untreated chronic-phase CML,” wrote Jorge E. Cortes, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues.
The phase III BFORE trial included 536 patients with newly diagnosed disease randomly assigned to 400-mg bosutinib once daily (n = 268) or imatinib (n = 268). Efficacy was assessed in patients who were Philadelphia chromosome–positive with typical transcripts.
At 12 months, 47.2% of patients assigned bosutinib achieved major molecular response compared with 36.9% of patients assigned imatinib (P = .02). Rates of major molecular response were higher with bosutinib for patients with high-, intermediate-, and low-risk Sokal risk scores. The cumulative incidence function of major molecular response was also more favorable with bosutinib than imatinib (hazard ratio [HR], 1.34; 95% CI, 1.06–1.69), which indicated a shorter time to response.
The rate of complete cytogenetic response was also higher at 12 months in patients assigned bosutinib compared with imatinib (77.2% vs 66.4%; P = .0075). Again, the cumulative incidence function of complete cytogenetic response was more favorable for bosutinib (HR, 1.38; 95% CI, 1.13–1.69).
About one-quarter of patients receiving bosutinib (22%) and imatinib (26.8%) discontinued treatment, most commonly due to drug-related toxicity (12.7% and 8.7%, respectively). However, dose interruptions were more common in patients assigned bosutinib, with 56.3% of patients having one or more dose interruptions compared with 35.8% of patients assigned imatinib. Patients assigned to bosutinib also experienced more grade 3 or worse diarrhea (7.8% vs 0.8%) and increased alanine aminotransferase (19.0% vs 1.5%) and aspartate aminotransferase (9.7% vs 1.9%) levels compared with imatinib.
“We conclude that bosutinib 400 mg once daily provides benefit over imatinib, with higher rates of cytogenetic and molecular responses, and that these responses occur earlier,” the researchers wrote. “Bosutinib is associated with a favorable toxicity profile, with most adverse events being low-grade, manageable, and improving over time.”