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
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Study 200 Efficacy


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

Proven efficacy in patients who have had prior TKI therapy

2nd line​​​​​​​

BOSULIF® (bosutinib) treated patients were able to achieve MCyR after treatment with imatinib (n=262 evaluable)*

  • 65% of responders had an MCyR lasting at least 18 months
  • 43% of responders had an MCyR lasting at least 54 months​​​​​​​

Median duration of MCyR was not reached at the time of analysis1

62% (n=96) of patients who achieved MCyR at any time (n=156) stayed on BOSULIF for at least 5 years1,2

Transformation rates were low in patients treated with BOSULIF2†
  • 95% of patients remained in CP while taking BOSULIF (n=269 out of 284)
    – 5% of patients in CP had confirmed disease transformation to AP or BP disease while taking BOSULIF (n=15 out of 284)

*Median duration of treatment was 26 months for evaluable patients.

Transformation rates for CP 2nd-line patients.

AP=accelerated phase; BP=blast phase; CI=confidence interval; MCyR=major cytogenetic response; Ph+=Philadelphia chromosome–positive; TKI=tyrosine kinase inhibitor.​​​​​​​

3rd line​​​​​​​

BOSULIF treated patients were able to achieve MCyR after treatment with imatinib followed by dasatinib or nilotinib (n=112 evaluable)1*

  • 64% of responders had an MCyR lasting at least 9 months
  • 36% of responders had an MCyR lasting at least 42 months​​​​​​​

Median duration of MCyR was not reached at the time of analysis1

Transformation rates were low in patients treated with BOSULIF2†
  • 96% of patients remained in CP while taking BOSULIF (n=114 out of 119)
    – 4% of patients in CP had confirmed disease transformation to AP or BP disease while taking BOSULIF (n=5 out of 119)

*Median duration of treatment was 9 months for evaluable patients.

Transformation rates for CP 3rd-line patients.

AP=accelerated phase; BP=blast phase; CI=confidence interval; MCyR=major cytogenetic response.​​​​​​​

Advanced phase​​​​​​​

Proven hematologic response rates with BOSULIF (n=132 evaluable)

Transformation rates were low in patients treated with BOSULIF2
  • 96% of patients in AP taking BOSULIF did not have confirmed disease transformation to BP
    ​​​​​​​– 4% of patients had confirmed disease transformation to BP while taking BOSULIF (n=3 out of 79)

OHR was defined as MHR (CHR + no evidence of leukemia) or RCP. All responses were confirmed after 4 weeks. CHR for AP and BP CML: WBC count ≤ institutional ULN, platelets ≥100,000/mm3 and <450,000/mm3, ANC ≥1.0 × 109/L, no blasts or promyelocytes in peripheral blood, <5% myelocytes + metamyelocytes in bone marrow, <20% basophils in peripheral blood, and no extramedullary involvement. No evidence of leukemia: meets all other criteria for CHR except may have thrombocytopenia (platelets ≥20,000/mm3 and <100,000/mm3) and/or neutropenia (ANC ≥0.5 × 109/L and <1.0 × 109/L). RCP was defined as disappearance of features defining AP or BP but still in CP.1

​​​​​​​ANC=absolute neutrophil count; AP=accelerated phase; BP=blast phase; CHR=complete hematologic response; MHR=major hematologic response; OHR=overall hematologic response; Ph+=Philadelphia chromosome–positive; RCP=return to chronic phase; ULN=upper limit of normal; WBC=white blood cell.

References​​​​​​​

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

Study 200 safety 

Including long-term, cardiac, and vascular data 

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Dosing and administration

Convenient once-daily dosing

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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.