IN NEWLY DIAGNOSED ADULT PATIENTS WITH CP Ph + CML ¹

MMR at 12 months is the primary endpoint and CCyR by 12 months is a secondary endpoint . MMR at 3 , 6 , 9 , and 18 months were prespecified exploratory analyses . MMR at 24 months and CCyR by 24 months are post hoc exploratory analyses of the ongoing BFORE trial . These exploratory analyses were not powered to detect statistical significance . No conclusion of efficacy can be drawn from these data . Lack of multiplicity adjustments can be a limitation of these analyses .

20

0

4.1 1.7

n = 10 n = 4 3

18.3

n = 86 n = 44 6 n = 104 n = 71 9

Month

n = 116 n = 89 12 n = 140 n = 115 n = 152 n = 128 18

24

* Derived from Cochran-Mantel-Haenszel test stratified by geographical region and Sokal risk score at randomization ; P values are 2-sided .

83 %

BOSULIF ( 95 % CI , 77.8-87.3 ) n = 246

77 %

Imatinib ( 95 % CI , 71.4-82.1 ) n = 241

Study design : BFORE is a randomized , 2-arm , open-label , multicenter ongoing trial in adult patients with newly diagnosed CP Ph + CML . Patients received 400 mg / day of BOSULIF or 400 mg / day of imatinib . Efficacy was assessed in the modified intent-to-treat ( mlTT ) population , which included 487 patients . ¹

IMPORTANT SAFETY INFORMATION

Contraindication : History of hypersensitivity to BOSULIF . Reactions have included anaphylaxis . Anaphylactic shock occurred in less than 0.2 % of treated patients in single-agent cancer studies with BOSULIF .

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 3 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 ]). In a study of BOSULIF in combination with letrozole , one drug-induced liver injury occurred without alternative causes . In the study of patients with newly diagnosed CP Ph + CML , the incidence of ALT / AST elevations was 31 % and 23 %, respectively . In patients with CML who were resistant or intolerant to prior therapy , the incidence of ALT / AST

Please see the Brief Summary of Prescribing Information on the following pages .

elevations was 18 % and 15 %, respectively . Twenty percent of the patients resistant or intolerant to prior therapy 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 .

Cardiac Failure : Cardiac failure and left ventricular dysfunction have been reported in patients taking BOSULIF . 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 . In a randomized study with newly diagnosed CML , cardiac failure occurred in 1.5 % of patients treated with BOSULIF compared to 0.8 % of patients treated with imatinib . 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 .

Fluid Retention : Fluid retention occurs with BOSULIF and may cause 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 .