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INDICATION

BOSULIF ® ( bosutinib ) is indicated for the treatment of adult patients with newly diagnosed chronic phase ( CP ) Ph + chronic myelogenous leukemia ( CML ). This indication is approved under accelerated approval based on molecular and cytogenetic response rates . Continued approval for this indication may be contingent upon verification and confirmation of clinical benefit in an ongoing long-term follow-up trial .

NCCN Clinical Practice Guidelines in Oncology ( NCCN Guidelines ®): Bosutinib ( BOSULIF ) is recommended by the NCCN Guidelines as a primary treatment option for patients with newly diagnosed CML ( category 1 ). ⁴

Cases of diarrhea occurred early in treatment and discontinuation rates remained low ^1-3

• 3 days : Median time to onset of diarrhea in the BOSULIF arm at 12 months ( range , 1-505 )

• 3 days : Median duration of diarrhea in the BOSULIF arm at 12 months ( range , 1-436 )

• 1 % of patients : Discontinued due to diarrhea in the BOSULIF arm at 12 months ( n = 2 )

Additional safety information ¹

• Of patients receiving BOSULIF who experienced transaminase elevations of any grade , 79 % experienced their first event within the first 3 months

• Patients with uncontrolled or significant cardiovascular disease , including prolonged QT interval , were excluded by protocol

• Cardiac failure occurred in 1.5 % of patients treated with BOSULIF compared to 0.8 % of patients treated with imatinib

DOSING

Tablet shown is not actual size .

The recommended starting dose for newly diagnosed patients with CP Ph + CML is 400 mg once daily with food . See Prescribing Information for starting dose adjustments . † 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 ).

AR = adverse reaction ; BFORE = Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment ; CCyR = complete cytogenetic response ; HLGT = high-level group term ; MedDRA = Medical Dictionary for Regulatory Activities ; MMR = major molecular response ; NCCN = National Comprehensive Cancer Network ; NEC = not elsewhere classified ; Ph += Philadelphia chromosome – positive ; SMQ = standardized MedDRA query ; SOC = system organ class .

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 .

Embryofetal Toxicity : BOSULIF can cause fetal harm . Women of childbearing potential should be advised of the potential hazard to the fetus and 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 observed in greater than or equal to 20 % of patients with newly diagnosed CML were diarrhea , nausea , thrombocytopenia , rash , increased ALT , abdominal pain , and increased AST . The most common Grade 3 / 4 adverse reactions and laboratory abnormalities observed in greater than 10 % of newly diagnosed CML patients were increased ALT and thrombocytopenia . The most common adverse reactions observed in greater than or equal to 20 % of patients with CML who were resistant

or intolerant to prior therapy were diarrhea , nausea , abdominal pain , rash , thrombocytopenia , vomiting , anemia , fatigue , pyrexia , cough , headache , increased ALT , and edema . The most common Grade 3 / 4 adverse reactions and laboratory abnormalities observed in greater than 10 % of patients who were resistant or intolerant to prior therapy were thrombocytopenia , neutropenia , and anemia .

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 .

References : 1 . BOSULIF Prescribing Information . New York , NY : Pfizer Inc . 2 . 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 . 3 . Data on file . Pfizer Inc ., New York , NY . 4 . Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology ( NCCN Guidelines ®) for Chronic Myeloid Leukemia V . 2.2020 . © National Comprehensive Cancer Network , Inc . 2019 . All rights reserved . Accessed February 3 , 2020 . To view the most recent and complete version of the guidelines , go online to NCCN . org . NCCN makes no warranties of any kind whatsoever regarding their content or its use or application and disclaims any responsibility for its use or application in any way . 5 . 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

PP-BOS-USA-0636-02 © 2020 Pfizer Inc . All rights reserved . Printed in USA / February 2020

For more information , visit BosulifHCP . com