Study 200 safety

In a phase 1/2 trial in adults with CP, AP, or BP Ph+ CML resistant or intolerant to prior therapy

Long-term safety data

The most common ARs with BOSULIF are well-established1
Warnings and precautions for BOSULIF include gastrointestinal toxicity, myelosuppression, hepatic toxicity, cardiac failure, fluid retention, renal toxicity, and embryofetal toxicity
ALT=alanine aminotransferase; AP=accelerated phase; AR=adverse reaction; BP=blast phase; Ph+=Philadelphia chromosome–positive.
Diarrhea
Diarrhea (all grades) was the most common adverse reaction, occurring in 82% (450 out of 546) of patients receiving BOSULIF1,2
90% (406 out of 450) of patients who developed diarrhea had a maximum severity of Grade 1 or 2, and there were no Grade 4 cases2
More than half of these patients (249 out of 450) had a maximum severity of Grade 12
Monitor and manage patients using standards of care, including antidiarrheals, antiemetics, and fluid replacement. Withhold, dose reduce, or discontinue BOSULIF as necessary1
Patients experiencing diarrhea (n=450)2
Learn more about select adverse reactions, including therapy management suggestions and dose adjustments, click here.
NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events.
Fluid retention1
5% (n=26) of patients had severe (grade 3/4) fluid retention
4% (n=21) of patients experienced grade 3 or 4 pleural effusion
1% (n=7) of patients experienced grade 3 or 4 pericardial effusion
1% (n=6) of patients experienced grade 3 edema
How to manage fluid retention1
To manage fluid retention, monitor and manage patients using standards of care. Interrupt, dose reduce, or discontinue BOSULIF as necessary.
References
1.
BOSULIF Prescribing Information. New York, NY: Pfizer Inc.
2.
Data on file. Pfizer Inc, New York, NY.

Long-term cardiac and vascular TEAEs

BOSULIF has long-term cardiac and vascular safety data2
Patients with uncontrolled or significant cardiovascular disease, including prolonged QT interval, were excluded by protocol.1
Long-term follow-up of adult patients with CP Ph+ CML and with advanced leukemias2
The long-term follow-up data analysis was based on a minimum of ~8 years (94 months) for patients with CP CML treated with 1 prior TKI (imatinib) and a minimum of 7 years (84 months) for patients with CP CML treated with imatinib and at least 1 additional TKI and for patients with advanced phase CML
Total extended safety population (N=570) included patients with CP Ph+ CML (n=403) and advanced Ph+ leukemias (AP CML [n=79], BP CML [n=64], and ALL [n=24])*
Cardiac failure and left ventricular dysfunction have been reported in patients taking BOSULIF® (bosutinib). These events occurred more frequently in previously treated patients than in patients with newly diagnosed CML and were more frequent in patients with advanced age or risk factors, including previous medical history of cardiac failure.1
In a single-arm study in patients with CML who were resistant or intolerant to prior therapy, cardiac failure was observed in 5.3% of patients treated with BOSULIF. Monitor patients for signs and symptoms consistent with cardiac failure and treat as clinically indicated. Interrupt, dose reduce, or discontinue BOSULIF as necessary.1
*BOSULIF is not indicated for the treatment of ALL.1
~8-year follow-up.
7-year follow-up.
§Cardiac includes MedDRA HLGTs in cardiac arrhythmias, heart failures, pericardial disorders; SOC in general disorders and administration site conditions and MedDRA PT in cardiac death, sudden cardiac death, sudden death; MedDRA SOC in investigations and MedDRA PT in ejection fraction decreased or PT MedDRA (SMQ) torsade de pointes/QT prolongation (narrow).
Grade 5 TEAEs are deaths.
Vascular includes MedDRA HLGTs in coronary artery disorders, arteriosclerosis, stenosis, vascular insufficiency and necrosis, embolism and thrombosis, HLT in arterial therapeutic procedures (excluding aortic), central nervous system hemorrhages and cerebrovascular accidents, central nervous system vascular disorders NEC, nonsite-specific vascular disorders NEC, peripheral vascular disorders NEC (excluding the 2 PTs flushing and hot flash), transient cerebrovascular events, vascular imaging procedures NEC, vascular therapeutic procedures NEC, PT in intestinal ischemia, subarachnoid hemorrhage, transcatheter arterial chemoembolization.
#Hypertension includes MedDRA SOC in investigations and HLGT in cardiac and vascular investigations (excluding enzyme tests) and HLT in vascular tests NEC (including blood pressure) and PT of blood pressure abnormal, blood pressure ambulatory abnormal, blood pressure ambulatory increased, blood pressure diastolic abnormal, blood pressure diastolic increased, blood pressure increased, blood pressure systolic abnormal, blood pressure systolic increased; SOC in vascular disorders and HLGT in vascular hypertensive disorders.
AdvP CML=advanced phase chronic myelogenous leukemia; ALL=acute lymphoblastic leukemia; AP=accelerated phase; BP=blast phase; HLGT=high-level group term; HLT=high-level term; MedDRA=Medical Dictionary for Regulatory Activities; NEC=not elsewhere classified; Ph+=Philadelphia chromosome-positive; PT=preferred term; SMQ=standardized MedDRA query; SOC=system organ class; TEAE=treatment-emergent adverse event; TKI=tyrosine kinase inhibitor.
Patients with known risk factors for cardiac and vascular events tend to have the highest incidence of cardiac and vascular complications3
Close monitoring, particularly in high-risk patients, and proactive management should be standard of care before starting therapy.3
References
1.
BOSULIF Prescribing Information. New York, NY: Pfizer Inc.
2.
Data on file. Pfizer Inc, New York, NY.
3.
Cortes JE, Khoury HJ, Kantarjian H, et al. Long-term evaluation of cardiac and vascular toxicity in patients with Philadelphia chromosome-positive leukemias treated with bosutinib. Am J Hematol. 2016;91(6):606-616.