4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Bosulif is indicated for the treatment of adult patients with:
• newly-diagnosed chronic phase (CP) Philadelphia chromosome-positive chronic myelogenous leukaemia (Ph+ CML).
• CP, accelerated phase (AP), and blast phase (BP) Ph+ CML previously treated with one or more tyrosine kinase inhibitor(s) [TKI(s)] and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Mechanism of action
Bosutinib inhibits the abnormal BCR-ABL kinase that promotes CML. Modeling studies indicate that bosutinib binds the kinase domain of BCR-ABL.
Clinical efficacy
Clinical study in CP previously untreated CML
- Bosutinib 400 mg study
The trial randomised 536 patients (268 in each treatment group) with Ph+ or Ph- newly-diagnosed CP CML (intent-to-treat population [ITT]) including 487 patients with Ph+ CML harbouring b2a2 and/or b3a2 transcripts and baseline BCR-ABL copies > 0 (modified intent-to-treat [mITT] population).
- AP and BP CML patients
Based on the limited clinical information from the Phase 1/2 study, some evidence of clinical activity was observed in patients with BCR-ABL mutations (see Table 6).
Table 6 - Response by baseline BCR-ABL mutation status in CP CML evaluable population: prior imatinib and dasatinib and/or nilotinib (third-line)
|
BCR-ABL mutation status at
baseline
|
Incidence at baseline n (%)a
|
MCyR attained or maintained
Resp/Evalb (%)
N=112
|
|
Mutation assessed
|
96 (100.0)
|
34/92 (37.0)
|
|
No mutation
|
57 (59.4)
|
21/55 (38.2)
|
|
At least 1 mutation
|
39 (40.6)
|
13/37 (35.1)
|
|
Dasatinib resistant mutations
|
10 (10.4)
|
1/9 (11.1)
|
|
E255K/V
|
2 (2.0)
|
0/2
|
|
F317L
|
8 (8.3)
|
1/7 (14.3)
|
|
Nilotinib resistant mutationsc
|
13 (13.5)
|
8/13 (61.5)
|
|
Y253H
|
6 (6.3)
|
5/6 (83.3)
|
|
E255K/V
|
2 (2.0)
|
0/2
|
|
F359C/I/V
|
7 (7.3)
|
5/7 (71.4)
|
Snapshot date: 02Oct2015
Note: Baseline mutations were identified before the patient's first dose of study drug.
Abbreviations: BCR-ABL=breakpoint cluster region-Abelson; CP=chronic phase; CML=chronic myelogenous
leukaemia; MCyR=major cytogenetic response; N/n=number of patients; Resp=responders; Eval=evaluable.
a The percentage is based on number of patients with baseline mutation assessment.
b The evaluable population includes patients who had a valid baseline disease assessment.
c 2 patients had more than 1 mutation in this category.
PACKAGE LEAFLET
1. What Bosulif is and what it is used for
Bosulif contains the active substance bosutinib. It is used to treat adult patients who have a type of leukaemia called Philadelphia chromosome positive (Ph-positive) Chronic Myeloid Leukaemia (CML) and for whom previous medicines have either not worked or are not suitable. Ph–positive CML is a cancer of the blood which makes the body produce too many of a specific type of white blood cell called granulocytes.