Bosutinib versus Imatinib in Treating Chronic Myeloid Leukemia

Chicago—After 30 months, patients with Philadelphia chromosome-positive chronic phase chronic myeloid leukemia who took bosutinib had superior efficacy and safety results compared with those who received imatinib, according to updated findings from an open-label, randomized, multinational, phase 3 trial.

Results were presented at the ASCO meeting during a poster session. The poster was titled BELA Trial Update: Bosutinib Versus Imatinib in Patients with Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia after 30 Months of Follow-Up. Bosutinib is an investigational oral medication; imatinib is an FDA-approved oral tyrosine kinase inhibitor.

The BELA (Bosutinib Efficacy and Safety in Chronic Myeloid Leukemia) study included patients ≥18 years of age who had no prior anti-proliferative treatment (other than <6 months of hydroxyurea or anagrelide), an Eastern Cooperative Oncology Group Performance Status of 0 or 1, and adequate hepatic and renal function.

They were randomized in a 1:1 ratio to receive starting doses of 500 mg per day of bosutinib (n=250) or 400 mg per day of imatinib (n=252). If no grade 3 or 4 adverse events occurred, patients were permitted to escalate the daily doses to 600 mg of bosutinib or imatinib.

The groups were well balanced. The median age was 48 years, approximately 55% of patients were male, and approximately 65% were white; median time to diagnosis was 23 days. The median treatment duration was 30.4 months in the bosutinib group and 30.6 months in the imatinib group. At 30 months, 62% of patients in the bosutinib group (n=155) and 70% of patients in the imatinib group (n=176) remained on treatment.

At 30 months, 56% of patients who received bosutinib and 61% of patients who took imatinib had a complete cytogenetic response (CCyR), while the cumulative CCyR was 79% and 81%, respectively. In addition, 45% of patients in the bosutinib group and 43% of patients in the imatinib group had a molecular response at 30 months, while the cumulative molecular response was 61% and 52%, respectively.

The median on-treatment event-free survival and the median overall survival had not been reached in either arm after 30 months. In the bosutinib group, 9 people had died: 5 due to chronic myeloid leukemia progression, while the other 4 were due to an adverse event (AE) unrelated to treatment. In the imatinib group, 13 people had died: 10 were due to chronic myeloid leukemia progression, while the other 3 were due to an AE unrelated to treatment and a suspicion of lung embolism.

Compared with the imatinib group, patients taking bosutinib had higher incidences of diarrhea, vomiting, abdominal pain, and pyrexia and lower incidences of muscle cramps, myalgia, bone pain, hypophosphatemia, elevated creatinine kinase, and edema. The authors noted that the toxicities in the bosutinib group occurred early during the treatment period. After the first year, few patients had new AEs or discontinued the study.

This study was supported by Pfizer Inc.