Custom Email Manager Email Template
An exploratory subgroup analysis.
ABRAXANE is indicated for the first-line treatment of patients with metastatic adenocarcinoma
of the pancreas, in combination with gemcitabine.
An Established First-Line
Standard of Care With a Survival
Benefit in the ITT Population1,2
ABRAXANE (125 mg/m2 QW 3/4) + gemcitabine
significantly increased median OS vs gemcitabine alone
PRESPECIFIED EXPLORATORY* KPS SUBGROUPS SHOWED CONSISTENT SURVIVAL BENEFIT WITH THE ITT POPULATION1,3
Median OS (95% CI) by KPS subgroups
* Analysis limitations: An exploratory analysis should not be interpreted to determine a treatment difference between arms
in these selected subgroups because of potential selection
bias, insufficient sample size, and a higher probability of making a false positive finding.
aStratified using Cox proportional hazard model.
bBased on a stratified log-rank test (stratified by geographic region, KPS, and
presence of liver metastasis)
MPACT STUDY DESIGN:
Randomized phase III study of ABRAXANE + gemcitabine vs gemcitabine alone in first-line metastatic pancreatic cancer (N=861). Primary endpoint was OS. ABRAXANE (125 mg/m2) + gemcitabine (1000 mg/m2) was given QW3/4. In the gemcitabine arm, gemcitabine (1000 mg/m2) was given QW7/8 and QW3/4.
CI=confidence interval; HR=hazard ratio; KPS=Karnofsky Performance Status Scale; OS=overall survival; PS=performance status; ITT=intention-to-treat.
IMPORTANT SAFETY INFORMATION
WARNING - NEUTROPENIA
Do not administer ABRAXANE therapy to patients who have baseline neutrophil counts of less than 1500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE
Note: An albumin
form of paclitaxel
may substantially
affect a drug’s
functional properties
relative to those of
drug in solution.
DO NOT SUBSTITUTE
FOR OR WITH OTHER
PACLITAXEL
FORMULATIONS
EXAMINE OS IN
A POST-HOC
SUBGROUP
ANALYSIS OF
PATIENTS WHO
WENT ON TO
RECEIVE
SUBSEQUENT
2L THERAPY.
LEARN MORE
IMPORTANT SAFETY INFORMATION
WARNING - NEUTROPENIA
Do not administer ABRAXANE therapy to patients who have baseline neutrophil
counts of less than 1500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving ABRAXANE
Note: An albumin form of paclitaxel may substantially affect a drug’s functional properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER PACLITAXEL FORMULATIONS
CONTRAINDICATIONS
Neutrophil Counts
ABRAXANE should not be used in patients who have baseline neutrophil counts of
<1500 cells/mm3
Hypersensitivity
Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with the drug
WARNINGS AND PRECAUTIONS
Hematologic Effects
Bone marrow suppression (primarily neutropenia) is dose-dependent and a dose-limiting
toxicity of ABRAXANE. In a clinical study, Grade 3-4 neutropenia occurred in 38% of patients
with pancreatic cancer
Monitor for myelotoxicity by performing complete blood cell counts frequently, including prior to
dosing on Days 1, 8, and 15 for pancreatic cancer
Do not administer ABRAXANE to patients with baseline absolute neutrophil counts (ANC) of less than 1500 cells/mm3
In patients with adenocarcinoma of the pancreas, withhold ABRAXANE and gemcitabine if the ANC is less than 500 cells/mm3 or platelets are less than 50,000 cells/mm3 and delay initiation of the next cycle if the ANC is less than 1500 cells/mm3 or platelet count is less than 100,000 cells/mm3 on Day 1 of the cycle. Resume treatment with appropriate dose reduction if recommended
Nervous System
Sensory neuropathy is dose- and schedule-dependent
The occurrence of Grade 1 or 2 sensory neuropathy does not generally require dose modification
If ≥ Grade 3 sensory neuropathy develops, withhold ABRAXANE treatment until resolution to ≤ Grade 1 followed by a dose reduction for all subsequent courses of ABRAXANE
Sepsis
Sepsis occurred in 5% of patients with or without neutropenia who received ABRAXANE in combination with gemcitabine
Biliary obstruction or presence of biliary stent were risk factors for severe or fatal sepsis
If a patient becomes febrile (regardless of ANC), initiate treatment with broad-spectrum antibiotics
For febrile neutropenia, interrupt ABRAXANE and gemcitabine until fever resolves and ANC ≥1500 cells/mm3, then resume treatment at reduced dose levels
Pneumonitis
Pneumonitis, including some cases that were fatal, occurred in 4% of patients receiving ABRAXANE in combination with gemcitabine
Monitor patients for signs and symptoms and interrupt ABRAXANE and gemcitabine during evaluation of suspected pneumonitis
Permanently discontinue treatment with ABRAXANE and gemcitabine upon making a diagnosis of pneumonitis
Hypersensitivity
Severe and sometimes fatal hypersensitivity reactions, including anaphylactic reactions,
have been reported
Patients who experience a severe hypersensitivity reaction to ABRAXANE should not be rechallenged with this drug
Hepatic Impairment
Because the exposure and toxicity of paclitaxel can be increased with hepatic impairment, administration of ABRAXANE in patients with hepatic impairment should be performed with
caution
Patients with hepatic impairment may be at an increased risk of toxicity, particularly from myelosuppression, and should be monitored for development of profound myelosuppression
For pancreatic adenocarcinoma, ABRAXANE is not recommended for patients with moderate to severe hepatic impairment (total bilirubin >1.5 x ULN and AST ≤10 x ULN)
Albumin (Human)
ABRAXANE contains albumin (human), a derivative of human blood
Use in Pregnancy: Pregnancy Category D
ABRAXANE can cause fetal harm when administered to a pregnant woman
If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus
Women of childbearing potential should be advised to avoid becoming pregnant while receiving ABRAXANE
Use in Men
Men should be advised not to father a child while receiving ABRAXANE
ADVERSE REACTIONS
Among the most common (≥20%) adverse reactions in the phase III study, those with a ≥5% higher incidence in the ABRAXANE/gemcitabine group compared with the gemcitabine group are neutropenia (73%, 58%), fatigue (59%, 46%), peripheral neuropathy (54%, 13%), nausea (54%, 48%), alopecia (50%, 5%), peripheral edema (46%, 30%), diarrhea (44%, 24%), pyrexia (41%, 28%), vomiting (36%, 28%), decreased appetite (36%, 26%), rash (30%, 11%), and dehydration (21%, 11%)
Of these most common adverse reactions, those with a ≥2% higher incidence of Grade 3-4 toxicity in the ABRAXANE/gemcitabine group compared with the gemcitabine group, respectively, are neutropenia (38%, 27%), fatigue (18%, 9%), peripheral neuropathy (17%, 1%), nausea (6%, 3%), diarrhea (6%, 1%), pyrexia (3%, 1%), vomiting (6%, 4%), decreased appetite (5%, 2%), and dehydration (7%, 2%)
Thrombocytopenia (all grades) was reported in 74% of patients in the ABRAXANE/gemcitabine group vs 70% of patients in the gemcitabine group
The most common serious adverse reactions of ABRAXANE (with a ≥1% higher incidence) are pyrexia (6%), dehydration (5%), pneumonia (4%), and vomiting (4%)
The most common adverse reactions resulting in permanent discontinuation of ABRAXANE were peripheral neuropathy (8%), fatigue (4%), and thrombocytopenia (2%)
The most common adverse reactions resulting in dose reduction of ABRAXANE are neutropenia (10%) and peripheral neuropathy (6%)
The most common adverse reactions leading to withholding or delay in ABRAXANE dosing are neutropenia (16%), thrombocytopenia (12%), fatigue (8%), peripheral neuropathy (15%), anemia (5%), and diarrhea (5%)
Other selected adverse reactions with a ≥5% higher incidence for all-grade toxicity in the ABRAXANE/gemcitabine group compared to the gemcitabine group, respectively, are asthenia (19%, 13%), mucositis (10%, 4%), dysgeusia (16%, 8%), headache (14%, 9%), hypokalemia (12%, 7%), cough (17%, 7%), epistaxis (15%, 3%), urinary tract infection (11%, 5%), pain in extremity (11%, 6%), arthralgia (11%, 3%), myalgia (10%, 4%), and depression (12%, 6%)
Other selected adverse reactions with a ≥2% higher incidence for Grade 3-4 toxicity in the ABRAXANE/gemcitabine group compared to the gemcitabine group are thrombocytopenia (13%, 9%), asthenia (7%, 4%), and hypokalemia (4%, 1%)
Postmarketing Experience With ABRAXANE and Other Paclitaxel Formulations
Severe and sometimes fatal hypersensitivity reactions have been reported with ABRAXANE. The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or human albumin has not been studied
There have been reports of congestive heart failure, left ventricular dysfunction, and atrioventricular block with ABRAXANE, primarily among individuals with underlying cardiac history or prior exposure to cardiotoxic drugs
There have been reports of extravasation of ABRAXANE. Given the possibility of extravasation, it is advisable to monitor closely the ABRAXANE infusion site for possible infiltration during drug administration
DRUG INTERACTIONS
Caution should be exercised when administering ABRAXANE concomitantly with medicines known to inhibit or induce either CYP2C8 or CYP3A4
USE IN SPECIFIC POPULATIONS
Nursing Mothers
It is not known whether paclitaxel is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother
Pediatric
The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated
Geriatric
Diarrhea, decreased appetite, dehydration, and epistaxis were more frequent in patients 65 years or older compared with patients younger than 65 years old who received ABRAXANE and gemcitabine in adenocarcinoma of the pancreas
Renal Impairment
There are insufficient data to permit dosage recommendations in patients with severe renal impairment or end stage renal disease (estimated creatinine clearance <30 mL/min)
DOSAGE AND ADMINISTRATION
Do not administer ABRAXANE to patients with metastatic adenocarcinoma of the pancreas who have moderate to severe hepatic impairment
Do not administer ABRAXANE to any patient with total bilirubin greater than 5 x ULN or AST greater than 10 x ULN
Dose reductions or discontinuation may be needed based on severe hematologic, neurologic, cutaneous, or gastrointestinal toxicity
Monitor patients closely
Please see full Prescribing Information, including Boxed WARNING.
You are encouraged to report negative side effects of prescription drugs to the FDA.
Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
To learn more, visit ABRAXANEPRO.com.
References: 1. Von Hoff DD, Ervin TJ, Arena FP, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691-1702. 2. Data on file. IntrinsiQ Monthly Market Share report. Ending June 2016. 3. Tabernero J, Chiorean EG, Infante JR, et al. Prognostic factors of survival in a randomized phase III TRIAL (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer. Oncologist. 2015;20(2):143-150.
ABRAXANE® is a registered trademark of Celgene Corporation.
© 2018 Celgene Corporation
06/18 US-ABR-18-0092
This e-mail was sent by Celgene Corporation
and is intended for US healthcare providers only.
Celgene Corporation, 86 Morris Avenue,
Summit, New Jersey 07901
x