BFORE efficacy and study design

MMR and CCyR
In an ongoing phase 3 trial of adult patients with newly diagnosed CP Ph+ CML,
Patients taking BOSULIF had higher rates of molecular and cytogenetic responses vs imatinib1,2
BOSULIF significantly improved MMR and CCyR1
24-month MMR and CCyR were post hoc exploratory analyses
These 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.
The 24-month data analysis, while not prespecified in the protocol, is from the ongoing BFORE trial and is presented to provide additional information about BOSULIF and its use in newly diagnosed Ph+ CML patients.3
Cumulative transformation rates
After a minimum of 12 months of follow-up, 5 BOSULIF® (bosutinib) patients and 7 imatinib patients transformed to AP or BP CML while on treatment1
After 24 months of follow-up, 6 and 7 patients transformed to AP or BP CML on BOSULIF and imatinib, respectively2
*Derived from Cochran-Mantel-Haenszel test stratified by geographical region and Sokal risk score at randomization; P values are 2-sided.
AP=accelerated phase; BFORE=Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment; BP=blast phase; CCyR=complete cytogenetic response; CI=confidence interval; MMR=major molecular response; Ph+=Philadelphia chromosome–positive.
MMR, MR4, and MR4.5 over time
More patients reached the 12-month MMR treatment milestone with BOSULIF vs imatinib1-3
Primary endpoint
In the BFORE study, MMR at 12 months was the primary endpoint.
Exploratory analyses
MMR at 3, 6, 9, and 18 months were prespecified exploratory analyses. MMR at 24 months is a post hoc exploratory analysis of the ongoing BFORE trial. These 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.
BFORE=Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment; MMR=major molecular response; MR=molecular response; Ph+=Philadelphia chromosome–positive.
MR4 and MR4.5 over time2,3
Exploratory analyses
MR4 and MR4.5 at 3, 6, 9, and 12 months were prespecified exploratory analyses. MR4 and MR4.5 at 24 months are post hoc exploratory analyses of the ongoing BFORE trial. These 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.
BFORE=Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment; MR=molecular response.
Study Design
BFORE: an ongoing phase 3 study of BOSULIF in newly diagnosed adult patients with CP Ph+ CML1
A randomized, 2-arm, open-label, multicenter trial conducted to investigate the efficacy and safety of BOSULIF vs imatinib
536 patients were randomized to receive 400 mg of BOSULIF® (bosutinib) or imatinib once daily
The primary endpoint was evaluated in a modified intent-to-treat (mITT) population of patients with Ph+ CML (n=487)
Primary endpoint
MMR at 12 months
Secondary endpoints
CCyR by month 12
MMR by month 18
Duration of CCyR and MMR
EFS
OS
Exploratory endpoints
MMR at month 12 (ITT population; N=536)
MMR at 3, 6, 9, and 18 months
MR4 and MR4,5 at 3, 6, 9, and 12 months
Time to MMR and CCyR
Time to on-treatment transformation to AP or BP CML
MMR at 12 months was defined as ≤0.1% BCR-ABL ratio on the International Scale (corresponding to a ≥3-log reduction from standardized baseline) with a minimum of 3000 ABL transcripts assessed by the central laboratory. CCyR was defined as the absence of Ph+ metaphases in chromosome banding analysis of ≥20 metaphases derived from bone marrow aspirate, or MMR if an adequate cytogenetic assessment was unavailable. MR4 was defined as ≤0.01% BCR-ABL1 transcripts on the International Scale with ≥9800 ABL1 assessed; MR4.5 was defined as ≤0.0032% BCR-ABL1 transcripts on the International Scale with ≥30,990 ABL1 assessed.1,3
AP=accelerated phase; BCR-ABL=breakpoint cluster region-Abelson: BFORE=Bosutinib Trial in First-Line Chronic Myelogenous Leukemia Treatment; BP=blast phase; CCyR=complete cytogenetic response; ECOG PS=Eastern Cooperative Oncology Group performance status; EFS=event-free survival; mITT=modified intent-to-treat; MMR=major molecular response; MR=molecular response; OS=overall survival; Ph+=Philadelphia chromosome–positive.
BOSULIF was studied in a population representing a clinical spectrum of patients with CP CML1,3
BFORE included patients with comorbidities and across all Sokal risk groups
Patients with uncontrolled or significant cardiovascular disease, including prolonged QT interval, were excluded by protocol.1
*NOTE: Data are n (%) unless noted otherwise. mITT population includes Ph+ patients with typical (e13a2 and/or e14a2) BCR-ABL1 transcript types.
Data missing for 1 patient in the imatinib arm.
Per case report form collected at screening if the patient had history of coronary disease.
BCR-ABL=breakpoint cluster region-Abelson; Ph+=Philadelphia chromosome–positive
References
1.
BOSULIF Prescribing Information. New York, NY: Pfizer Inc.
2.
Data on file. Pfizer Inc., New York, NY.
3.
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.