Cardiac, vascular, and hypertension safety of bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia in the BFORE trial.

Abstract

7051 Background: Tyrosine kinase inhibitor therapy has been linked to cardiac and vascular events. Cardiac, vascular and hypertension treatment-emergent adverse events (TEAEs) with bosutinib or imatinib for newly diagnosed chronic phase chronic myeloid leukemia were analyzed. Methods: Patients (pts) who received ≥1 dose of bosutinib (n = 268) or imatinib (n = 265) 400 mg/d in the phase 3 BFORE trial were included. Prespecified MedDRA terms comprised the clusters of investigator assessed TEAEs. Exposure-adjusted TEAE rate was defined as the number of pts with TEAEs / total pt-yr (pt-yr = sum of total time to first TEAE for pts with TEAEs and treatment duration for pts without TEAEs). Results: After ≥36 mo follow-up, 65% vs 62% of pts in the bosutinib vs imatinib arm were still on treatment. Rates of TEAEs, treatment withdrawals and drug-related TEAEs in the clusters of interest were low in both arms (Table). The most common cardiac, vascular and hypertension TEAEs, respectively, were sinus bradycardia (2%), angina pectoris (3%) and hypertension (7%) vs prolonged QT (3%), peripheral coldness (1%) and hypertension (9%) with bosutinib vs imatinib; corresponding grade 3/4/5 TEAE rates in the respective clusters were 3%, 3% and 4% vs 1%, 0.4% and 4%. Hypertension was the only grade 3/4 TEAE occurring in ≥1% of pts in either arm (4% each); 1 grade 5 TEAE each was noted for bosutinib (cardiac failure) and imatinib (cerebrovascular accident). Exposure-adjusted rates of cardiac, vascular and hypertension TEAEs, respectively, were 0.04, 0.03 and 0.04 vs 0.03, 0.01 and 0.04 (grade 3/4/5 only: 0.01, 0.01 and 0.02 vs 0.01, 0.002 and 0.02) for bosutinib vs imatinib. Conclusions: Cardiac, vascular and hypertension TEAE rates were low with bosutinib and imatinib. A majority of TEAEs were low grade and few led to treatment withdrawal. Clinical trial information: NCT02130557. [Table: see text]