SAN DIEGO, CA—At the 53rd American Society of Hematology Annual Meeting and Exposition, Jorge E. Cortes, MD of the MD Anderson Cancer Center, Houston, TX, and colleagues presented 24-month follow-up data from the BELA Trial. The BELA trial evaluated the efficacy of bosutinib, an oral, dual competitive inhibitor of the Src and Abl tyrosine kinases, in newly diagnosed chronic phase chronic myeloid leukemia (CP-CML). Dr. Cortes reported that though the study did not meet the primary endpoint of complete cytogenic response (CCyR) at 12 months, bosutinib treatment resulted in a higher rate of major molecular response (MMR), faster times to MMR and CCyR, fewer events of transformation to accelerated phase/blastic phase (AP/BP) CML, and fewer overall and CML-related deaths compared with imatinib.

The Phase 3, open-label  study compared bosutinib 500mg/day with imatinib 400mg/day in 502 patients with newly diagnosed CP-CML. Patients were randomized 1:1 and stratified by Sokal score risk group (low, medium, high) and geographical region. The primary efficacy endpoint was CCyR at 12 months in the intent-to-treat population. Key secondary and exploratory efficacy endpoints included MMR at 12 months, time to CCyR and MMR, duration of CCyR and MMR, time to and incidence of transformation to AP/BP CML, event-free survival (EFS), and overall survival.

Median treatment duration was 27.5 months (range <0.1–41.3) for bosutinib and 27.5 months (range 0.5–38.8) for imatinib; 62% and 71% of patients, respectively, are currently still receiving therapy. Discontinuation of therapy in the bosutinib group was primarily due to toxicity (24%), whereas the primary reason for discontinuation of imatinib was disease progression (13%).

At 24 months, the rate of cumulative CCyR was 79% and 80% in the bosutinib and imatinib arms, respectively. The cumulative rate of MMR by 24 months, however, was 61% in the bosutinib group compared with 50% in the imatinib group. Faster median times to CCyR and MMR for bosutinib versus imatinib were also observed. (See Table). Transformation to AP/BP CML while on treatment occurred in four (2%) patients on bosutinib compared with 13 (5%) patients receiving imatinib. Additionally, study investigators reported that the 24-month estimates for EFS and OS currently favor bosutinib. Deaths due to any cause occurred in seven patients receiving bosutinib versus 13 patients receiving imatinib, and included six and ten patients, respectively, who died due to disease progression. Kaplan-Meier estimates of OS at 24 months for bosutinib and imatinib were 97% versus 95%, respectively.

Bosutinib and imatinib demonstrated distinct toxicity profiles. Bosutinib was associated with higher incidences of pyrexia (18% vs 12%) and gastrointestinal events compared with imatinib: diarrhea (70% vs. 29%, respectively), vomiting (32% vs 16%), and abdominal pain (13% vs 7%). Bosutinib, however, was associated with lower incidences of edema (peripheral edema [4% vs 11%] and periorbital edema [1% vs. 15%]) and musculoskeletal events (myalgia [6% vs 12%], muscle cramps [4% vs 22%], and bone pain [4% vs 10%]).

Grade 3/4 neutropenia occurred less frequently in patients on bosutinib (10% vs 24% with imatinib), while the incidences of Grade 3/4 anemia and thrombocytopenia were similar between treatment arms. Grade 3/4 liver function test abnormalities occurred more frequently with bosutinib versus imatinib (increased alanine aminotransferase [23% vs 4%] and aspartate aminotransferase [12% vs 4%]). Gastrointestinal events and liver function test abnormalities, common with bosutinib therapy, were typically transient, managed with dose modifications, and not life threatening.