BFORE safety

Warnings and precautions for BOSULIF include gastrointestinal toxicity, myelosuppression, hepatic toxicity, cardiac failure, fluid retention, renal toxicity, and embryofetal toxicity
In an ongoing Phase 3 trial of adult patients with newly diagnosed CP Ph+ CML,
Most common adverse reactions for BOSULIF vs imatinib1,2
Clinically relevant laboratory test abnormalities
By the 12-month analysis, 1 patient receiving BOSULIF® (bosutinib) died vs 6 patients receiving imatinib3
By 24 months, 3 patients receiving BOSULIF died vs 9 patients receiving imatinib2
Discontinuation rates due to ARs2,3
Cases of diarrhea occurred early in treatment and discontinuation rates remained low2,3
At 12 months, 1% of patients discontinued due to diarrhea3
At 24 months, 1% of patients discontinued due to diarrhea2
Diarrhea was manageable (primarily grade 1 or 2). Monitor and manage patients using standards of care, including antidiarrheals, antiemetics, and fluid replacement. Withhold, dose reduce, or discontinue BOSULIF as necessary1,3
Rates of fluid retention2,3
In the first 12 months, 1 patient receiving BOSULIF (0.4%) experienced severe fluid retention of grade 3 pericardial effusion1
At 24 months, severe fluid retention (grade ≥3) was experienced by 2 patients (0.7%) for BOSULIF: grade 3 pericardial effusion and pleural effusion. For imatinib, 1 patient (0.4%) experienced grade 3 peripheral edema2
Most cases of transaminase elevations occurred early in treatment1-3
Of patients receiving BOSULIF who experienced transaminase elevations of any grade, 79% experienced their first event within the first 3 months1
– The median time to onset of increased ALT and AST was 32 and 43 days, respectively, and the median duration was 20 and 15 days, respectively1
Incidence of cardiac and vascular§ TEAEs1-4
In the first 12 months, cardiac events that were grade ≥3 were pericardial effusion (n=1) and supraventricular tachycardia (n=1) in the BOSULIF arm and QTc prolongation (n=1) in imatinib patients3
At 24 months, grade ≥3 cardiac events were electrocardiogram QT prolonged (n=1), atrial fibrillation (n=2), pericardial effusion (n=1), cardiac failure (n=2, one of which was death), cardiorespiratory arrest (n=1), pleuropericarditis (n=1), and supraventricular tachycardia (n=1) for BOSULIF. For imatinib, grade ≥3 cardiac events were electrocardiogram QT prolonged (n=1), atrial fibrillation (n=1), and supraventricular tachycardia (n=1)2
Cardiac failure occurred in 1.5% of patients treated with BOSULIF compared to 0.8% of patients treated with imatinib1
One patient in the group treated with BOSULIF experienced a grade 3 QTc prolongation (>500 msec)1,2
Patients with uncontrolled or significant cardiovascular disease, including prolonged QT interval, were excluded by protocol1
*Rash includes the following preferred terms: acne, dermatitis, dermatitis acneiform, dermatitis allergic, dermatitis exfoliative, drug reaction with eosinophilia and systemic symptoms, photosensitivity reaction, rash, rash erythematous, rash generalized, rash macular, rash maculo-papular, rash papular, rash pruritic, urticaria.
Inclusive of MedDRA (SMQ) hepatic disorders.
Includes MedDRA HLGTs cardiac arrhythmias, heart failures, and pericardial disorders under the SOC cardiac disorders; the preferred terms cardiac death, sudden cardiac death, sudden death, and ejection fraction decreased; and the standardized MedDRA query torsade de pointes/QT prolongation (narrow).
§Cardiovascular includes the MedDRA HLGT coronary artery disorders. Cerebrovascular includes the high-level terms central nervous system hemorrhages and cerebrovascular accidents, central nervous system vascular disorders NEC, transient cerebrovascular events, vascular imaging procedures NEC, and vascular therapeutic procedures NEC. Peripheral vascular includes the HLGTs arteriosclerosis, stenosis, vascular insufficiency and necrosis, and embolism and thrombosis as well as the high-level terms arterial therapeutic procedures (excluding aortic), nonsite-specific vascular disorders NEC, and peripheral vascular disorders NEC (excluding flushing and hot flash).
ALT=alanine aminotransferase; AR=adverse reaction; AST=aspartate aminotransferase; HLGT=high-level group term; MedDRA=Medical Dictionary for Regulatory Activities; NEC=not elsewhere classified; Ph+=Philadelphia chromosome–positive; SGOT=serum glutamic-oxaloacetic transaminase; SGPT=serum glutamic-pyruvic transaminase; SOC=system organ class; SMQ=standardized MedDRA query; TEAE=treatment emergent adverse event; ULN=upper limit of normal.
References
1.
BOSULIF Prescribing Information. New York, NY: Pfizer Inc.
2.
Data on file. Pfizer Inc, New York, NY.
3.
Cortes JE, Gambacorti-Passerini C, Deininger MW, et al. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial. J Clin Oncol. 2018;36(3):231-237.
4.
Cortes JE, Gambacorti-Passerini C, Deininger MW, et al. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: results from the randomized BFORE trial. J Clin Oncol. 2018;36(3):231-237, Data Supplement. Accessed February 3, 2020. https://ascopubs.org/doi/suppl/10.1200/JCO.2017.74.7162