Multiple presentations evaluate the
investigational uses of ABRAXANE alone or as combination therapy to
treat non-small cell lung cancer and as combination therapy for
locally advanced pancreatic cancer
Celgene Corporation (NASDAQ:CELG) today announced that data from
multiple studies evaluating investigational uses of ABRAXANE®
(paclitaxel protein-bound particles for injectable suspension)
(albumin-bound) will be presented during the European Society of
Medical Oncology (ESMO) 2017 Annual Meeting between September 8-12
in Madrid, Spain.
"The data presented at ESMO highlight investigational uses of
ABRAXANE to potentially treat patients with particularly
challenging diseases, either alone or in combination with other
agents," said Nadim Ahmed, President, Hematology and Oncology for
Celgene. "Through these data, we are able to continue advancing our
understanding and treatment of these cancers especially in patient
populations with historically limited treatment options."
In advanced non-small cell lung cancer (NSCLC), abstracts from
three studies in the ABOUND program continue to evaluate
investigational uses of ABRAXANE. ABOUND 2L+ is a Phase II trial
evaluating second-line monotherapy or combination treatment with an
immune checkpoint inhibitor or epigenetic therapy. ABOUND.SQM is a
Phase III study evaluating ABRAXANE as combination treatment with
carboplatin as induction therapy for those with squamous disease.
ABOUND 70+ is a Phase IV study evaluating the first-line treatment
of ABRAXANE + carboplatin in patients 70 years and older.
Additionally, updated data from the Phase II LAPACT study
evaluating the investigational use of ABRAXANE in patients with
locally advanced, non-resectable pancreatic cancer will be
presented.
Selected abstracts include*:
Non-Small Cell Lung Cancer
Abstract LBA48; Oral; Friday, September 8, 4:00 p.m.,
Madrid Auditorium, ABOUND.2L+: nab-paclitaxel (nap-P) +/- CC-486 or
durvalumab in previously treated patients with advanced non-small
cell lung cancer (NSCLC) (Morgensztern)
Abstract 1369P; Poster; Saturday, September 9, 1:15 p.m.,
Hall 8, nab-Paclitaxel/carboplatin (nab-P/C) induction therapy in
squamous (SCC) non-small cell lung cancer (NSCLC): interim safety
results from ABOUND.sqm (Gridelli)
Abstract 1366P; Poster; Saturday, September 9, 1:15
p.m., Hall 8, Effect of nab-paclitaxel/carboplatin (nab-P/C)
induction therapy on quality of life (QoL) of patients with
squamous (SCC) non-small cell lung cancer (NSCLC) (ABOUND.sqm)
(Ponce Aix)
Abstract 1367P; Poster; Saturday, September 9, 1:15 p.m.,
Hall 8, Quality of Life (QoL) in Elderly NSCLC Patients (pts)
Treated with nab-Paclitaxel/Carboplatin (nab-P/C) in the ABOUND.70+
Trial (Langer)
Pancreatic Cancer
Abstract 622PD; Poster Discussion; Monday, September 11, 4:30
p.m., Cordoba Auditorium, nab-Paclitaxel (nab-P) plus gemcitabine
(G) for patients (Pts) with locally advanced pancreatic cancer
(LAPC): Interim efficacy and safety results from the Phase 2 LAPACT
Trial (Philip)
Abstract 730P; Poster; Saturday, September 9, 1:15
p.m., Hall 8, Interim Health-Related Quality of Life (QoL) From
LAPACT, a Phase 2 Trial of nab-Paclitaxel (nab-P) Plus Gemcitabine
(G) for Patients (pts) With Locally Advanced Pancreatic Cancer
(LAPC) (Portales)
In advanced NSCLC, Abraxane is not approved for use as
monotherapy or in combination with CC-486 or durvalumab. Abraxane
is also not approved for use as a second-line therapy in advanced
NSCLC. Abraxane is not approved for patients with locally advanced
pancreatic cancer. The safety and efficacy of the agents and/or
uses under investigation have not been established. There is no
guarantee that the agents will receive health authority approval or
become commercially available in any country for the uses being
investigated.
*All times Central European Standard Time (CEST)
A complete listing of abstracts can be found on the ESMO website
at
http://194.224.142.195/slidecenter/esmo2017/confcal/?table.
About ABRAXANE® (paclitaxel protein-bound
particles for injectable suspension) (albumin-bound)
ABRAXANE® is an albumin-based nanotechnology therapy
approved for the treatment of metastatic breast cancer, advanced
non-small cell lung cancer and metastatic pancreatic cancer
in the United States, Europe and other markets
around the world. It contains albumin-bound paclitaxel
nanoparticles and is manufactured using
patented nab® technology. ABRAXANE is formulated
with albumin, a human protein, and is free of solvents.
ABRAXANE was first approved in January 2005 by
the U.S. Food and Drug Administration (FDA) for the
treatment of breast cancer after failure of combination
chemotherapy for metastatic disease or relapse within 6 months of
adjuvant chemotherapy. Prior therapy should have included an
anthracycline unless clinically contraindicated. In Europe,
ABRAXANE was approved in January 2008 as monotherapy for
the treatment of metastatic breast cancer in adult patients who
have failed first-line treatment for metastatic disease and for
whom standard, anthracycline containing therapy is not indicated.
ABRAXANE is now approved in more than 50 countries for the
treatment of metastatic breast cancer.
In October 2012, ABRAXANE was approved by
the FDA for the first-line treatment of locally advanced
or metastatic non-small cell lung cancer (NSCLC), in combination
with carboplatin, in patients who are not candidates for curative
surgery or radiation therapy. ABRAXANE is also approved for the
treatment of NSCLC in Argentina, Australia, Chile, Ecuador,
Guatemala, Hong Kong, Japan, New
Zealand and Singapore.
In September 2013, the FDA approved ABRAXANE as
first-line treatment of patients with metastatic adenocarcinoma of
the pancreas, in combination with gemcitabine. In December
2013, ABRAXANE in combination with gemcitabine was approved for
first-line treatment of adult patients with metastatic
adenocarcinoma of the pancreas in Europe. ABRAXANE
is also approved for the treatment of metastatic pancreatic cancer
in more than 40 countries.
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 clinical studies, Grade 3-4 neutropenia occurred in
34% of patients with metastatic breast cancer (MBC), 47% of
patients with non–small cell lung cancer (NSCLC), and 38% of
patients with pancreatic cancer
- Monitor for myelotoxicity by performing
complete blood cell counts frequently, including prior to dosing on
Day 1 (for MBC) and Days 1, 8, and 15 (for NSCLC and for pancreatic
cancer)
- Do not administer ABRAXANE to patients
with baseline absolute neutrophil counts (ANC) of less than 1500
cells/mm3
- In the case of severe neutropenia
(<500 cells/mm3 for 7 days or more) during a course of ABRAXANE
therapy, reduce the dose of ABRAXANE in subsequent courses in
patients with either MBC or NSCLC
- In patients with MBC, resume treatment
with every-3-week cycles of ABRAXANE after ANC recovers to a level
>1500 cells/mm3 and platelets recover to a level
>100,000 cells/mm3
- In patients with NSCLC, resume
treatment if recommended at permanently reduced doses for both
weekly ABRAXANE and every-3-week carboplatin after ANC recovers to
at least 1500 cells/mm3 and platelet count of at least 100,000
cells/mm3 on Day 1 or to an ANC of at least 500 cells/mm3 and
platelet count of at least 50,000 cells/mm3 on Days 8 or 15 of the
cycle
- 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
or 2 for MBC or until resolution to ≤ Grade 1 for NSCLC and
pancreatic cancer 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 MBC and NSCLC, the starting dose
should be reduced for patients with moderate or severe hepatic
impairment
- 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
Randomized Metastatic Breast Cancer (MBC) Study
- The most common adverse reactions
(≥20%) with single-agent use of ABRAXANE vs paclitaxel injection in
the MBC study are alopecia (90%, 94%), neutropenia (all cases 80%,
82%; severe 9%, 22%), sensory neuropathy (any symptoms 71%, 56%;
severe 10%, 2%), abnormal ECG (all patients 60%, 52%; patients with
normal baseline 35%, 30%), fatigue/asthenia (any 47%, 39%; severe
8%, 3%), myalgia/arthralgia (any 44%, 49%; severe 8%, 4%), AST
elevation (any 39%, 32%), alkaline phosphatase elevation (any 36%,
31%), anemia (any 33%, 25%; severe 1%, <1%), nausea (any 30%,
22%; severe 3%, <1%), diarrhea (any 27%, 15%; severe <1%, 1%)
and infections (24%, 20%), respectively
- Sensory neuropathy was the cause of
ABRAXANE discontinuation in 7/229 (3%) patients
- Other adverse reactions of note with
the use of ABRAXANE vs paclitaxel injection included vomiting (any
18%, 10%; severe 4%, 1%), fluid retention (any 10%, 8%; severe 0%,
<1%), mucositis (any 7%, 6%; severe <1%, 0%), hepatic
dysfunction (elevations in bilirubin 7%, 7%), hypersensitivity
reactions (any 4%, 12%; severe 0%, 2%), thrombocytopenia (any 2%,
3%; severe <1%, <1%), neutropenic sepsis (<1%, <1%),
and injection site reactions (<1%, 1%), respectively.
Dehydration and pyrexia were also reported
- Renal dysfunction (any 11%, severe 1%)
was reported in patients treated with ABRAXANE (n=229)
- In all ABRAXANE-treated patients
(n=366), ocular/visual disturbances were reported (any 13%; severe
1%)
- Severe cardiovascular events possibly
related to single-agent ABRAXANE occurred in approximately 3% of
patients and included cardiac ischemia/infarction, chest pain,
cardiac arrest, supraventricular tachycardia, edema, thrombosis,
pulmonary thromboembolism, pulmonary emboli, and hypertension
- Cases of cerebrovascular attacks
(strokes) and transient ischemic attacks have been reported
Non–Small Cell Lung Cancer (NSCLC) Study
- The most common adverse reactions
(≥20%) of ABRAXANE in combination with carboplatin are anemia,
neutropenia, thrombocytopenia, alopecia, peripheral neuropathy,
nausea, and fatigue
- The most common serious adverse
reactions of ABRAXANE in combination with carboplatin for NSCLC are
anemia (4%) and pneumonia (3%)
- The most common adverse reactions
resulting in permanent discontinuation of ABRAXANE are neutropenia
(3%), thrombocytopenia (3%), and peripheral neuropathy (1%)
- The most common adverse reactions
resulting in dose reduction of ABRAXANE are neutropenia (24%),
thrombocytopenia (13%), and anemia (6%)
- The most common adverse reactions
leading to withholding or delay in ABRAXANE dosing are neutropenia
(41%), thrombocytopenia (30%), and anemia (16%)
- The following common (≥10% incidence)
adverse reactions were observed at a similar incidence in ABRAXANE
plus carboplatin–treated and paclitaxel injection plus
carboplatin–treated patients: alopecia (56%), nausea (27%), fatigue
(25%), decreased appetite (17%), asthenia (16%), constipation
(16%), diarrhea (15%), vomiting (12%), dyspnea (12%), and rash
(10%); incidence rates are for the ABRAXANE plus carboplatin
treatment group
- Adverse reactions with a difference of
≥2%, Grade 3 or higher, with combination use of ABRAXANE and
carboplatin vs combination use of paclitaxel injection and
carboplatin in NSCLC are anemia (28%, 7%), neutropenia (47%, 58%),
thrombocytopenia (18%, 9%), and peripheral neuropathy (3%, 12%),
respectively
- Adverse reactions with a difference of
≥5%, Grades 1-4, with combination use of ABRAXANE and carboplatin
vs combination use of paclitaxel injection and carboplatin in NSCLC
are anemia (98%, 91%), thrombocytopenia (68%, 55%), peripheral
neuropathy (48%, 64%), edema peripheral (10%, 4%), epistaxis (7%,
2%), arthralgia (13%, 25%), and myalgia (10%, 19%),
respectively
- Neutropenia (all grades) was reported
in 85% of patients who received ABRAXANE and carboplatin vs 83% of
patients who received paclitaxel injection and carboplatin
Pancreatic Adenocarcinoma Study
- 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
- A higher incidence of epistaxis,
diarrhea, dehydration, fatigue, and peripheral edema was found in
patients 65 years or older who received ABRAXANE for MBC in a
pooled analysis of clinical studies
- Myelosuppression, peripheral
neuropathy, and arthralgia were more frequent in patients
≥65 years of age treated with ABRAXANE and carboplatin in
NSCLC
- 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 any
patient with total bilirubin greater than 5 x ULN or AST greater
than 10 x ULN
- For MBC and NSCLC, reduce starting dose
in patients with moderate to severe hepatic impairment
- For adenocarcinoma of the pancreas, do
not administer ABRAXANE to patients who have moderate to severe
hepatic impairment
- 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.
Please refer to the Summary of Product
Characteristics for full European prescribing
information.
About Celgene
Celgene Corporation, headquartered in Summit, New Jersey, is an
integrated global biopharmaceutical company engaged primarily in
the discovery, development and commercialization of innovative
therapies for the treatment of cancer and inflammatory diseases
through next-generation solutions in protein homeostasis,
immuno-oncology, epigenetics, immunology and neuro-inflammation.
For more information, please visit www.celgene.com. Follow Celgene
on Social Media: @Celgene, Pinterest, LinkedIn, FaceBook and
YouTube.
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outcomes may differ materially from those implied by the
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