Efficacy
Newly Diagnosed Adults with CP Ph+
CML
Ph+ CML in Adults With Resistance or
Intolerance to Prior Therapy
Safety
Newly Diagnosed Adults With CP Ph+ CML
Ph+ CML in Adults with Resistance or Intolerance to Prior Therapy
Support & Resources

BFORE Safety

Warnings and precautions for BOSULIF® (bosutinib) include gastrointestinal toxicity, myelosuppression, hepatic toxicity, cardiovascular toxicity, fluid retention, renal toxicity, and embryo-fetal toxicity.1
In newly diagnosed adults with CP Ph+ CML
Long-term safety with 5-year follow-up
​​​​​​​*Based on a minimum of 57 months of follow-up.
​​​​​​​ALT=alanine aminotransferase; AR=adverse reaction; AST=aspartate aminotransferase; CML=chronic myelogenous leukemia; CP=chronic phase; Ph+=Philadelphia chromosome–positive; SGOT=serum glutamic-oxaloacetic transaminase; SGPT=serum glutamic-pyruvic transaminase.
​​​​​​​Additional 5-year safety information
Treatment discontinuation2
  • The most common reasons for permanent discontinuation in the BFORE study were TEAEs and lack of efficacy
    • The rate of treatment discontinuation due to TEAEs was 25% in the BOSULIF arm and 12.5% in the imatinib arm
      • The majority of treatment discontinuations due to TEAEs occurred during the first year of  therapy and decreased over time
      • The most frequent TEAE leading to permanent treatment discontinuation was increased ALT (4.9%) with BOSULIF and thrombocytopenia (1.5%) with imatinib
    • 5.6% of BOSULIF patients discontinued treatment due to lack of efficacy vs 17.7% of imatinib patients
Cases of diarrhea occurred early in treatment and discontinuation rates remained low1,2
​​​​​​​THE RATES OF DIARRHEA (ALL GRADES) WERE 75% FOR BOSULIF AND 40% FOR IMATINIB1​​​​​
  • 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 necessary​​​​​​​1
​​​​​​​BFORE=Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment; CML=chronic myelogenous leukemia; CP=chronic phase; Ph+=Philadelphia chromosome–positive; TEAE=treatment-emergent adverse event.
Most cases of transaminase elevations occurred early in treatment1
THE RATES OF HEPATIC DYSFUNCTION ARs (ALL GRADES) WERE 45% FOR BOSULIF AND 15% FOR IMATINIB​​​​​​​1
  • Of patients who experienced transaminase elevations of any grade, 73% experienced their first event within the first 3 months
  • ​​​​​​​The median time to onset of increased ALT and AST was 29 and 56 days, respectively, and the median duration was 19 and 15 days, respectively
  • ​​​​​​​Perform hepatic enzyme tests monthly for the first 3 months of BOSULIF treatment and as clinically indicated. In patients with transaminase elevations, monitor liver enzymes more frequently. Withhold, dose reduce, or discontinue BOSULIF as necessary​​​​​​​​​​​​​​

Rates of fluid retention ARs1​​

  • Severe (grade 3) fluid retention occurred in 3 patients (1.1%) taking BOSULIF
  • Grade 3 pericardial effusion occurred in 1 patient taking BOSULIF
  • Grade 3 pleural effusion occurred in 2 patients taking BOSULIF
  • Monitor and manage patients using standards of care. Interrupt, dose reduce, or discontinue BOSULIF as necessary

Cardiovascular ARs1​​​​​​​

  • Cardiac failure occurred in 1.9% of patients treated with BOSULIF compared with 0.8% of patients treated with imatinib
  • Cardiac ischemic events occurred in 4.9% of patients treated with BOSULIF compared with 0.8% of patients treated with imatinib
  • One patient receiving BOSULIF experienced a grade 3 QTcF prolongation (>500 msec)
  • Patients with uncontrolled or significant cardiovascular disease, including QT interval prolongation, were excluded by protocol
  • Monitor patients for signs and symptoms consistent with cardiac failure and cardiac ischemia and treat as clinically indicated. Interrupt, dose reduce, or discontinue BOSULIF as necessary
ALT=alanine aminotransferase; AR=adverse reaction; AST=aspartate aminotransferase; CML=chronic myelogenous leukemia; CP=chronic phase; Ph+=Philadelphia chromosome–positive.

References

  1. BOSULIF Prescribing Information. New York, NY: Pfizer Inc.
  2. Data on file. Pfizer Inc., New York, NY.​​​​​​​

    Dosing and administration
    ​​​​​​​

    Convenient once-daily dosing

    ​​​​​​​Explore dosing options

    Therapy management
    ​​​​​​​

    Management considerations for selected adverse reactions associated with BOSULIF

    View considerations

    Indications

    BOSULIF® (bosutinib) is indicated for the treatment of adult patients with:

    • Newly diagnosed chronic phase (CP) Ph+ chronic myelogenous leukemia (CML)
    • Chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy

    Contraindications: History of hypersensitivity to BOSULIF. Reactions have included anaphylaxis.

    Gastrointestinal Toxicity: Diarrhea, nausea, vomiting, and abdominal pain occur with BOSULIF. In the study of patients with newly diagnosed CP Ph+ CML, the median time to onset for diarrhea (all grades) was 4 days and the median duration per event was 3 days. In the study of patients with CML who were resistant or intolerant to prior therapy, median time to onset of diarrhea (all grades) was 2 days, median duration was 2 days, and the median number of episodes per patient was 3 (range 1-268). Monitor and manage patients using standards of care, including antidiarrheals, antiemetics, and/or fluid replacement. Withhold, dose reduce, or discontinue BOSULIF as necessary.

    Myelosuppression: Thrombocytopenia, anemia, and neutropenia occur with BOSULIF. Perform complete blood counts weekly for the first month and then monthly thereafter, or as clinically indicated. Withhold, dose reduce, or discontinue BOSULIF as necessary.

    Hepatic Toxicity: BOSULIF may cause elevations in serum transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]). Out of 1711 patients in BOSULIF clinical trials, 2 cases consistent with drug-induced liver injury have occurred without alternative causes. In the study of patients with newly diagnosed CP Ph+ CML, the incidence of ALT and AST elevations was 68% and 56%, respectively. In patients with CML who were resistant or intolerant to prior therapy, the incidence of ALT and AST elevations was 53% and 47%, respectively; sixty percent of these patients experienced an increase in either ALT or AST. Perform hepatic enzyme tests at least monthly for the first 3 months and as clinically indicated. In patients with transaminase elevations, monitor liver enzymes more frequently. Withhold, dose reduce, or discontinue BOSULIF as necessary. In patients with mild, moderate, or severe hepatic impairment, the recommended starting dose is 200 mg daily

    Cardiovascular Toxicity: BOSULIF can cause cardiovascular toxicity, including cardiac failure, left ventricular dysfunction, and cardiac ischemic events. Cardiac failure 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. Cardiac ischemic events occurred in both previously treated patients and in patients with newly diagnosed CML and were more common in patients with coronary artery disease risk factors, including history of diabetes, body mass index greater than 30, hypertension, and vascular disorders. In a randomized study of patients with newly diagnosed CML, cardiac failure occurred in 1.9% of patients treated with BOSULIF compared to 0.8% of patients treated with imatinib. Cardiac ischemic events occurred in 4.9% of patients treated with BOSULIF compared to 0.8% of patients treated with imatinib. In a single-arm study of patients with CML who were resistant or intolerant to prior therapy, cardiac failure was observed in 5.3% of patients and cardiac ischemic events were observed in 4.9% of patients treated with BOSULIF. Monitor patients for signs and symptoms consistent with cardiac failure and cardiac ischemia and treat as clinically indicated. Interrupt, dose reduce, or discontinue BOSULIF as necessary.

    Fluid Retention: Fluid retention occurs with BOSULIF and may manifest as pericardial effusion, pleural effusion, pulmonary edema, and/or peripheral edema. Monitor and manage patients using standards of care. Interrupt, dose reduce, or discontinue BOSULIF as necessary.

    Renal Toxicity: An on-treatment decline in estimated glomerular filtration rate has occurred in patients treated with BOSULIF. Monitor renal function at baseline and during therapy, with particular attention to patients with preexisting renal impairment or risk factors for renal dysfunction. Lower starting doses are recommended for patients with renal impairment. For patients who have declining renal function while on BOSULIF or who cannot tolerate the starting dose, follow dose adjustment recommendations for toxicity.

    Embryo-Fetal Toxicity: BOSULIF can cause fetal harm. Women of childbearing potential should be advised of the potential risk to the fetus and advised to use effective contraceptive measures while on treatment and for at least 2 weeks after the final dose.

    Adverse Reactions: The most common adverse reactions, in ≥20% of patients with newly diagnosed CP Ph+ CML or CP, AP, or BP Ph+ CML with resistance or intolerance to prior therapy (N=814) were diarrhea (80%), rash (44%), nausea (44%), abdominal pain (43%), vomiting (33%), fatigue (33%), hepatic dysfunction (33%), respiratory tract infection (25%), pyrexia (24%), and headache (21%). The most common laboratory abnormalities that worsened from baseline in ≥20% of patients were creatinine increased (93%), hemoglobin decreased (90%), lymphocyte count decreased (72%), platelets decreased (69%), ALT increased (58%), calcium decreased (53%), white blood cell count decreased (52%), absolute neutrophil count decreased (50%), AST increased (50%), glucose increased (46%), phosphorus decreased (44%), urate increased (41%), alkaline phosphatase increased (40%), lipase increased (36%), creatine kinase increased (29%), and amylase increased (24%).

    CYP3A Inhibitors and Inducers: Avoid concurrent use with strong or moderate CYP3A inhibitors or strong CYP3A inducers.

    Proton Pump Inhibitors (PPIs): Consider using short-acting antacids or H2 blockers instead of PPIs to avoid a reduction in BOSULIF exposure. Separate antacid or H2 blocker dosing and BOSULIF dosing by more than 2 hours.

    Lactation: Because of the potential for serious adverse reactions in a nursing child, breastfeeding is not recommended during treatment with BOSULIF and for at least 2 weeks after the last dose.

    BOSULIF is indicated for the treatment of adult patients with:

    • Newly diagnosed chronic phase (CP) Ph+ chronic myelogenous leukemia (CML)
    • Chronic, accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy

    Please see full Prescribing Information.