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

Authors

null

Jorge E. Cortes

The University of Texas MD Anderson Cancer Center, Houston, TX

Jorge E. Cortes , Tim H. Brümmendorf , Carlo Gambacorti-Passerini , Richard E Clark , Eric Leip , Andrea Viqueira , Vamsi Kota , Michael W.N. Deininger

Organizations

The University of Texas MD Anderson Cancer Center, Houston, TX, Universitätsklinikum RWTH Aachen, Aachen, Germany, University of Milano-Bicocca, Monza, Italy, Royal Liverpool University Hospital, Liverpool, United Kingdom, Pfizer Inc., Cambridge, MA, Pfizer SLU, Madrid, Spain, Georgia Cancer Center at Augusta University, Augusta, GA, Oregon Health & Science University, Portland, UT

Research Funding

Pharmaceutical/Biotech Company

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

n (%)Bosutinib (n = 268)Imatinib (n = 265)
Any cardiac TEAE23 (9)17 (6)
Led to withdrawal1 ( < 1)0
Drug-related7 (3)6 (2)
Any vascular TEAE18 (7)8 (3)
Led to withdrawal3 (1)1 ( < 1)
Drug-related5 (2)0
Any hypertension TEAE22 (8)25 (9)
Led to withdrawal00
Drug-related2 (1)5 (2)

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Abstract Details

Meeting

2019 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Track

Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Sub Track

Chronic Leukemia—CML

Clinical Trial Registration Number

NCT02130557

Citation

J Clin Oncol 37, 2019 (suppl; abstr 7051)

DOI

10.1200/JCO.2019.37.15_suppl.7051

Abstract #

7051

Poster Bd #

426

Abstract Disclosures

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