ASH Clinical News August 2017 v3 | Page 5
Peer Review Week
September 11 – 17, 2017
Peer Review Week is an annual global event celebrating
the essential role that peer review plays in maintaining
scientific quality. The theme “Transparency in Review” will
be explored in virtual events, such as webinars and social
media activities, and in-person panel discussions that
coincide with the Peer Review Congress in Chicago, IL.
Advanced Practice Providers Oncology
Summit
The goal of this summit is to foster collaboration, share
best practices, and provide a forum for peer-to-peer
interaction among advanced practice providers who are
actively engaged in caring for oncology patients.
Upcoming Dates and Locations:
September 15 – 16, 2017
Denver, CO
7th International Symposium on
Acute Promyelocytic Leukemia
September 24 – 27, 2017
Rome, Italy
In addition to advances in biology and treatment of
acute promyelocytic leukemia, the meeting includes
updates on diagnostics, management, and minimal
residual disease assessment.
October 13 – 14, 2017
Portland, OR
”
G:.5”
S:6.75”
Adverse Reactions (10% or Greater) in Patients with CML in Study 1 (cont’d)
Chronic Phase CML
N=406
Back pain
Asthenia
Pruritus
Dizziness
Dyspnea
Advanced Phase CML
N=140
All Grades
(%) Grade 3/4
(%) All Grades
(%) Grade 3/4
(%)
12
11
11
10
10 1
1
1
0
1 7
10
8
13
19 1
1
0
1
6
Advanced phase (AdvP) CML includes patients with accelerated phase and blast phase CML
a. Abdominal pain includes the following preferred terms: abdominal pain, upper abdominal pain, lower abdominal pain,
abdominal tenderness, gastrointestinal pain, abdominal discomfort
b. Rash includes the following preferred terms: rash, macular rash, pruritic rash, generalized rash, papular rash,
maculo-papular rash
c. Fatigue includes the following preferred terms: fatigue, malaise
d. Edema includes the following preferred terms: edema, peripheral edema, localized edema, face edema
e. Respiratory tract infection includes the following preferred terms: respiratory tract infection, upper respiratory tract infection,
lower respiratory tract infection, viral upper respiratory tract infection, viral respiratory tract infection
In the single-arm, Phase 1/2 clinical trial, one patient (0.2%) experienced QTcF interval of greater than
500 ms. Patients with uncontrolled or significant cardiovascular disease, including QT interval
prolongation, were excluded by protocol.
Number (%) of Patients with Clinically Relevant or Severe Grade 3/4 Laboratory Test
Abnormalities in Patients with CML in Study 1, Safety Population
Chronic Phase CML
N=406
n (%)
102 (25)
74 (18) 52 (37) 126 (23)
53 (13) 49 (35) 102 (19)
39 (10)
17 (4)
33 (8) 8 (6)
4 (3)
4 (3) 47 (9)
21 (4)
37 (7)
30 (7) 10 (7) 40 (7)
3 (1) 2 (1) 5 (1)
Additional Adverse Reactions from Multiple Clinical Trials:
The following adverse reactions were reported in patients in clinical trials with BOSULIF (less than 10% of
BOSULIF-treated patients). They represent an evaluation of the adverse reaction data from 870 patients
with Ph+ leukemia who received at least 1 dose of single-agent BOSULIF. These adverse reactions are
presented by system organ class and are ranked by frequency. These adverse reactions are included
based on clinical relevance and ranked in order of decreasing seriousness within each category.
Blood and Lymphatic System Disorders: 1% and less than 10% - febrile neutropenia
Cardiac Disorders: 1% and less than 10% - pericardial effusion; 0.1% and less than 1% - pericarditis
Ear and Labyrinth Disorders: 1% and less than 10% - tinnitus
Gastrointestinal Disorders: 1% and less than 10% - gastritis; 0.1% and less than 1% - acute pancreatitis,
gastrointestinal hemorrhage a
General Disorders and Administrative Site Conditions: 1% and less than 10% - chest pain, b pain
Hepatobiliary Disorders: 1% and less than 10% - hepatotoxicity, c abnormal hepatic function d ; 0.1% and less
than 1% - liver injury
Immune System Disorders: 1% and less than 10% - drug hypersensitivity; 0.1% and less than 1% -
anaphylactic shock
Infections and Infestations: 1% and less than 10% - pneumonia, e influenza, bronchitis
Investigations: 1% and less than 10% - electrocardiogram QT prolonged, increased blood creatine
phosphokinase, increased blood creatinine
Metabolism and Nutrition Disorder: 1% and less than 10% - hyperkalemia, dehydration
Musculoskeletal and Connective Tissue Disorder: 1% and less than 10% - myalgia
Nervous System Disorders: 1% and less than 10% - dysgeusia
Renal and Urinary Disorders: 1% and less than 10% - acute renal failure, renal failure
Respiratory, Thoracic, and Mediastinal Disorders: 1% and less than 10% - pleural effusion; 0.1% and less than
1% - acute pulmonary edema, respiratory failure, pulmonary hypertension
Skin and Subcutaneous Disorders: 1% and less than 10% - urticaria, pruritus, acne; 0.1% and less than 1% -
erythema multiforme, exfoliative rash, drug eruption
a. Gastrointestinal hemorrhage includes the following preferred terms: gastrointestinal hemorrhage, gastric hemorrhage,
upper gastrointestinal hemorrhage
b. Chest pain includes the following preferred terms: chest pain, chest discomfort
c. Hepatotoxicity includes the following preferred terms: hepatotoxicity, toxic hepatitis, cytolytic hepatitis
d. Abnormal hepatic function includes the following preferred terms: abnormal hepatic function, liver disorder
e. Pneumonia includes the following preferred terms: pneumonia, bronchopneumonia, lobar pneumonia, primary
atypical pneumonia
DRUG INTERACTIONS
Drugs That May Increase Bosutinib Plasma Concentrations: CYP3A inhibitors: Avoid the concomitant use
of strong or moderate CYP3A inhibitors with BOSULIF as an increase in bosutinib plasma concentration
is expected. In a dedicated cross-over drug-interaction trial in healthy volunteers (N=24), concomitant
ketoconazole (strong CYP3A inhibitor) increased bosutinib C max 5.2-fold and AUC 8.6-fold compared to
BOSULIF alone. Drugs That May Decrease Bosutinib Plasma Concentrations: CYP3A Inducers: Avoid the
OVERDOSAGE
Experience with BOSULIF overdose in clinical studies was limited to isolated cases. There were no reports
of any serious adverse events associated with the overdoses. Patients who take an overdose of BOSULIF
should be observed and given appropriate supportive treatment.
PATIENT COUNSELING INFORMATION
See FDA-Approved Patient Labeling. Dosing and Administration: Instruct patients to take BOSULIF exactly
as prescribed, not to change their dose or to stop taking BOSULIF unless they are told to do so by their
doctor. If patients miss a dose beyond 12 hours, they should be advised to take the next scheduled dose at
its regular time. A double dose should not be taken to make up for any missed dose. Advise patients to
take BOSULIF with food. Patients should be advised: “Do not crush or cut tablet. Do not touch or handle
crushed or broken tablets.” Gastrointestinal Problems: Advise patients that they may experience
diarrhea, nausea, vomiting, abdominal pain, or blood in their stools with BOSULIF and to seek medical
attention promptly for these symptoms. Low Blood Cell Counts: Advise patients of the possibility of
developing low blood cell counts and to immediately report fever, any suggestion of infection, or signs or
symptoms suggestive of bleeding or easy bruising. Liver Problems: Advise patients of the possibility of
developing liver function abnormalities and to immediately report jaundice. Fluid Retention: Advise
patients of the possibility of developing fluid retention (swelling, weight gain, or shortness of breath) and
to seek medical attention promptly if these symptoms arise. Renal Problems: Advise patients of the
possibility of developing renal problems and to immediately report frequent urination, polyuria, or
oliguria. Other Adverse Reactions: Advise patients that they may experience other adverse reactions such
as respiratory tract infections, rash, fatigue, loss of appetite, headache, dizziness, back pain, arthralgia, or
pruritus with BOSULIF and to seek medical attention if symptoms are significant. There is a possibility of
anaphylactic shock. Pregnancy and Breast-feeding: Advise patients that BOSULIF can cause fetal harm
when administered to a pregnant woman. Advise women of the potential hazard to the fetus and to avoid
becoming pregnant. If BOSULIF is used during pregnancy, or if the patient becomes pregnant while taking
BOSULIF, the patient should be apprised of the potential hazard to the fetus. Because a potential risk to the
nursing infant cannot be excluded, women that are taking BOSULIF should not breast-feed or provide
breast milk to infants. Counsel females of reproductive potential to use effective contraceptive measures
to prevent pregnancy during and for at least 30 days after completing treatment with BOSULIF. Instruct
patients to contact their physicians immediately if they become pregnant during treatment. Advise
patients not to take BOSULIF treatment while pregnant or breast-feeding. If a patient wishes to restart
breast-feeding after treatment, advise her to discuss the appropriate timing with her physician.
Drug Interactions: Advise patients that BOSULIF and certain other medicines, including over-the-counter
medications or herbal supplements (such as St. John’s wort), can interact with each other and may alter
the effects of BOSULIF.
October 5 – 6, 2017
Buenos Aires, Argentina
The InterAmerican Oncology Conference focuses on
translational advances in the treatment of cancer,
as well as provides updates on targeted therapies,
immunotherapies, and emerging treatments in
early development.
American Association of Blood Banks
Annual Meeting
October 7 – 10, 2017
San Diego, CA
The AABB Annual Meeting brings together transfusion
specialists, laboratory supervisors, cellular therapy and
blood banking professionals, medical technologists,
donor recruiters, physicians, and nurses to advance
transfusion and cellular therapies worldwide.
CAP17: The Pathologists’ Meeting
October 8 – 11, 2017
National Harbor, MD
The College of American Pathologists’ 2017 meeting
brings together pathology and laboratory medicine
experts from around the world.
Towards Transformative Therapies for
Sickle Cell Disease
October 24, 2017
New York, NY
This one-day symposium discusses recent
developments in sickle cell disease, highlighting key
biological mechanisms of disease and reviewing
relevant clinical science, while also underscoring the
importance of the patient experience.
Clinical Application of CAR T Cells
November 16 – 17, 2017
New York, NY
Memorial Sloan Kettering faculty and national
and international experts will discuss clinical and
translational aspects of chimeric antigen receptors
(CARs), both for hematologic malignancies and
solid tumors.
182 (33)
7th InterAmerican Oncology Conference
80 (57)
USE IN SPECIFIC POPULATIONS
Pregnancy Category D: Based on its mechanism of action and findings in animals, BOSULIF can cause
fetal harm when administered to a pregnant woman. Studies in animals showed reproductive toxicities.
If BOSULIF is used during pregnancy, or if the patient becomes pregnant while taking BOSULIF, the patient
should be apprised of the potential hazard to the fetus. Fetal exposure to bosutinib-derived radioactivity
during pregnancy was demonstrated in a placental-transfer study in pregnant rats. Bosutinib was
administered orally to pregnant rats during the period of organogenesis at doses of 1, 3, and 10 mg/kg/day.
This study did not expose pregnant rats to enough bosutinib to fully evaluate adverse outcomes. In a
study conducted in rabbits, bosutinib was administered orally to pregnant animals during the period of
organogenesis at doses of 3, 10, and 30 mg/kg/day. At the maternally-toxic dose of 30 mg/kg/day
of bosutinib, there were fetal anomalies (fused sternebrae, and two fetuses had various visceral
observations), and an approximate 6% decrease in fetal body weight. The dose of 30 mg/kg/day resulted in
exposures (AUC) approximately 4 times those in humans at the 500 mg/day dose of bosutinib.
Nursing Mothers: It is not known whether bosutinib is excreted in human milk. Bosutinib and/or its
metabolites were excreted in the milk of lactating rats. Radioactivity was present in the plasma of suckling
offspring 24 to 48 hours after lactating rats received a single oral dose of radioactive bosutinib. Because
many drugs are excreted in human milk and because of the potential for serious adverse reactions in
nursing infants from BOSULIF, a decision should be made whether to discontinue nursing or to discontinue
the drug, taking into account the importance of the drug to the mother. Pediatric Use: The safety and
efficacy of BOSULIF in patients less than 18 years of age have not been established. Geriatric Use: In the
Phase 1/2 clinical trial of BOSULIF in patients with Ph+ CML, 20% were age 65 and over, and 4% were 75 and
over. No overall differences in safety or effectiveness were observed between these patients and younger
patients, and other reported clinical experience has not identified differences in responses between
the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Hepatic Impairment: Treat with a dose of 200 mg daily in patients with any baseline hepatic impairment.
In a dedicated hepatic impairment trial, the exposure to bosutinib increased (C max increased 1.5- to 2.3-fold
and the AUC increased 1.9- to 2.4-fold) in patients with hepatic impairment (Child-Pugh classes A, B, and
C; N=18) compared to matched healthy volunteers (N=9). Renal Impairment: Reduce the BOSULIF starting
dose in patients with severe (CrCL <30 mL/min) or moderate (CrCL 30-50 mL/min) renal impairment at
baseline. For patients who have declining renal function while on BOSULIF who cannot tolerate a 500-mg
dose, follow dose adjustment recommendations for toxicity. In a dedicated renal impairment trial,
compared to subjects with normal renal function, the exposure (AUC) of bosutinib increased by 60% and 35%
in subjects with CrCL <30 mL/min and CrCL 30-50 mL/min, respectively, compared to subjects with normal
renal function. BOSULIF has not been studied in patients undergoing hemodialysis.
September 24 – 27, 2017
San Diego, CA
The 58th ASTRO Annual Meeting creates a forum for
global collaboration on issues in radiation oncology.
Hematology Parameters
Platelet Count (Low)
less than 50 x 10 9 /L
Absolute Neutrophil Count
less than 1 x 10 9 /L
Hemoglobin (Low) less than 80 g/L
Biochemistry Parameters
SGPT/ALT greater than 5.0 x ULN
SGOT/AST greater than 5.0 x ULN
Lipase greater than 2 x ULN
Phosphorus (Low)
less than 0.6 mmol/L
Total Bilirubin greater than
3.0 x ULN
Advanced Phase CML All CP and AdvP CML
N=546
N=140
n (%)
n (%)
concomitant use of strong or moderate CYP3A inducers with BOSULIF as a large reduction in exposure
is expected. In a dedicated cross-over drug-interaction trial in healthy volunteers (N=24), concomitant
rifampin (strong CYP3A inducer) decreased bosutinib C max by 86% and AUC by 94% compared to BOSULIF
alone. Proton Pump Inhibitors: In a dedicated cross-over drug-interaction trial in healthy volunteers
(N=24), concomitant lansoprazole (PPI) decreased bosutinib C max by 46% and AUC by 26% compared to
BOSULIF alone. Consider using short-acting antacids or H2 blockers instead of PPIs to avoid a r eduction in
bosutinib exposure. Separate antacid or H2 blocker dosing and BOSULIF dosing by more than 2 hours.
American Society for Radiation Oncology
Annual Meeting
2017 American Society of
Hematology Annual Meeting
December 9 – 12, 2017
Atlanta, GA
The 59th ASH Annual Meeting and Exposition
will provide an invaluable educational experi-
ence and the opportunity to review thousands
of scientific abstracts highlighting updates in
the hottest topics in hematology.
Rx only
This brief summary is based on BOSULIF Prescribing Information LAB-0443-6.0, revised April 2016.
© 2016 Pfizer Inc. All rights reserved. May 2016
ASH Clinical News
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