CHICAGO—Bosutinib resulted in superior rates of major molecular response (MMR) and complete cytogenetic response (CCyR) compared with imatinib in patients with chronic phase chronic myeloid leukemia (CML). At the American Society of Clinical Oncology’s 2011 Annual Meeting, C. Gambacorti-Passerini, MD, from the University of Milan Bicocca, Monza, Italy, and colleagues reported that the faster rates of MMR and CCyR achieved with bosutinib correlates with a shorter risk period for disease transformation with bosutinib compared with imatinib.
In the Phase 3 BELA study, investigators compared bosutinib, a competitive dual Src/Abl kinase inhibitor, with imatinib in 502 patients with newly diagnosed chronic phase CML. Patients were stratified by Sokal score and region and then randomized to receive bosutinib 5mg/day (n=250) or imatinib 400mg/day (n=252). Study design and endpoints were described in a previously published abstract.1 Efficacy analyses included all randomized patients (intent-to-treat); safety analyses included all treated patients.
Median duration of treatment was 19.3 months for bosutinib (n=248) and 19.5 months for imatinib (n=251). At one year, CCyR rates were 70% for bosutinib and 68% for imatinib, at 18 months 62% and 67%, respectively; cumulative CCyR rates at 18 months were 79% for both bosutinib and imatinib. MMR rates at one year were significantly higher for bosutinib compared with imatinib (39% vs. 26%; P=0.002), as were cumulative MMR rates at 18 months (55% vs. 45%; P<0.05). Time to CCyR and MMR were significantly shorter with bosutinib (P <0.001 for both). Transformation to accelerated/blast phase occurred in 2% of patients on bosutinib and 5% of patients on imatinib. Treatment failure was observed to be greater in patients treated with imatinib (13% of patients) compared with bosutinib (4%).
Treatment-emergent adverse events (TEAEs; ≥10% of patients) observed with bosutinib and imatinib, respectively, were diarrhea (11%, 1%), vomiting (3%, 0%), nausea (1%, 0%), and rash (2%, 1%). Pleural effusions were seen in 3% of bosutinib patients (no imatinib patients). Median cumulative duration of diarrhea from Grade 3/4 to Grade 0/1 was 5 days for bosutinib and 9 days for imatinib. Grade ≥3 lab abnormalities (≥10% of patients) with bosutinib and imatinib, respectively, were elevated alanine aminotransferase (23%, 4%), thrombocytopenia (14%, 14%), elevated aspartate aminotransferase (11%, 3%), neutropenia (11%, 24%) and hypophosphatemia (4%, 18%). Discontinuation of therapy occurred in 29% of bosutinib patients and 20% of imatinib patients; the primary reason for discontinuation of bosutinib was AEs, while the primary reason for imatinib was disease progression. Deaths occurred in four (1.6%) bosutinib patients and 12 (4.8%) imatinib patients; overall, 81% died from disease progression.
Dr. Gambacorti-Passerini concluded that the efficacy and safety data of bosutinib from BELA were consistent with previously reported results. Bosutinib showed a significantly higher MMR rate at one year, significantly faster times to CCyR and MMR, and lower transformation rate vs. imatinib. Additionally, bosutinib had a distinct and acceptable toxicity profile and may offer a new therapeutic option in newly diagnosed Ph+ chronic phase CML.
1. ASH Accepted Abstract #208. An Ongoing Phase 3 Study of Bosutinib (SKI-606) Versus Imatinib in Patients with Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia. Oral Presentation. Carlo Gambacorti-Presenter. 52nd American Society of Hematology Annual Meeting. Orlando, FL. December 4-7, 2010.