BOUDRY, Switzerland--(BUSINESS WIRE)--Celgene Corporation (NASDAQ:CELG) today announced interim results from
the ABOUND clinical trial program evaluating the use of ABRAXANE®
(paclitaxel protein-bound particles for injectable suspension)
(albumin-bound) in patients with advanced non-small cell lung cancer
(NSCLC). Interim data being presented from the ABOUND trials during the
IASLC 17th World Conference on Lung Cancer (WCLC) reinforces
the benefit of ABRAXANE/carboplatin doublet therapy in first-line NSCLC.
“These early data from the ABOUND clinical trial program are very
encouraging, as they are consistent with the findings related to these
hard to treat non-small cell lung cancer patient subgroups seen in the
pivotal ABRAXANE Phase III trial”
Interim ABOUND.70+ data in 128 elderly patients (= 70 years old)
receiving first-line treatment with ABRAXANE/carboplatin for advanced
NSCLC found that 91 (73%) patients experienced grade =2 peripheral
neuropathy (PN) or grade =3 myelosuppression [primary endpoint]. At the
time of the analyses, the median overall survival was 14.6 months and
the median progression-free survival was 6.2 months, pooled across the
two treatment arms [secondary endpoints]. Patients were randomized to
receive first-line treatment with ABRAXANE/carboplatin either continuous
weekly or weekly every three weeks with a one-week break.i
Overall, 80 percent of patients discontinued treatment and the majority
did so due to adverse events (24 percent) or disease progression (34
percent). Grade =2 PN was reported in 34% of patients, and grade =3
neutropenia, anemia, and thrombocytopenia was observed in 52%, 21% and
21% of patients, respectively. i
The interim ABOUND.sqm data in 284 patients receiving first-line
induction treatment with ABRAXANE/carboplatin for stage IIIB/IV squamous
NSCLC showed that the safety profile was consistent with that previously
reported for the squamous subset in the pivotal Phase III trial.ii,iii
During the induction phase, all patients received four 21-day cycles of
standard ABRAXANE/carboplatin therapy.ii Overall, 119
patients (42 percent) discontinued treatment during the induction phase.
The majority of patients discontinued treatment due to disease
progression (34 percent) or adverse events (24 percent). The most common
grade 3/4 treatment emergent adverse events (TEAEs) were hematologic and
included anemia (26 percent), neutropenia (43 percent) and
thrombocytopenia (15 percent).ii
Both ABOUND trials also evaluated quality of life utilizing the Lung
Cancer Symptom 3-item index Scale (LCSS), Symptom Burden Index, Lung
Cancer Symptom and Pulmonary Symptom Scores and the EuroQol five
dimensions, five level questionnaire (EQ-5D-5L). These interim analyses
suggest that quality of life was generally maintained or improved in
both patient populations.iv,v
"These early data from the ABOUND clinical trial program are very
encouraging, as they are consistent with the findings related to these
hard to treat non-small cell lung cancer patient subgroups seen in the
pivotal ABRAXANE Phase III trial," said Michael Pehl, President,
Hematology and Oncology for Celgene. "These data, coupled with the
ongoing studies of ABRAXANE in combination with novel agents and
immunotherapies, provide us with a deeper understanding of how to treat
challenging patient populations and will help us continue to develop
future treatment options."
With the rapidly evolving lung cancer treatment landscape, Celgene
remains committed to continuing to explore new combinations that will
benefit those living with lung cancer, including patients who may not
benefit from immunotherapy and targeted therapy. ABRAXANE is being
actively evaluated as a foundation therapy in these patients.
Interim results of the phase I study of the immunotherapy agent
nivolumab in combination with ABRAXANE/carboplatin in 22 patients with
Stage IIIB/IV NSCLC will also be presented at WCLC. Patients received
four cycles of standard ABRAXANE/carboplatin therapy in combination with
nivolumab, followed by nivolumab monotherapy starting at cycle 5. The
primary endpoints were number of patients with dose limiting toxicity
and percentage of patients with grade 3/4 TEAEs or treatment
discontinuation due to a TEAE. The interim data suggests that combining
ABRAXANE/carboplatin with nivolumab may have promising anti-tumor
activity in patients with advanced NSCLC with no unexpected adverse
events (AEs).vi
The most common grade 3/4 AEs observed during the study included
neutropenia (45 percent), anemia (35 percent), hypokalemia (15 percent),
and vomiting (15 percent).vi The study has been expanded and
patients are currently enrolling in part 2. Additional data on the
safety and efficacy of this combination in multiple tumor types will be
presented at a future medical meeting.
Additional ABRAXANE Data Presented at WCLC
There will also be an oral presentation at WCLC focused on new findings
from the phase III registration study for ABRAXANE (Abstract 4460),
which reports on the impact of depth of response on survival in patients
with advanced NSCLC treated with first-line chemotherapy. Real-world
analyses of US veterans with NSCLC are also being presented at WCLC,
evaluating prevalence of squamous NSCLC in veterans vs. the general
population (Abstract 4737) and the prevalence of autoimmune
disease in veterans with NSCLC (Abstract 4745).
Additional investigator initiated studies presented at WCLC also
evaluated ABRAXANE as first-line (Posters P2.03a-028 and P2.06-018),
second-line (Posters P2.03a-040, P2.03a-054 and P2.03a-056)
or third-line (Poster P2.06-015) treatment for advanced NSCLC
patients, as well as in the adjuvant (Poster P2.03a-070) and
neoadjuvant (Poster P2.04-034) settings and in chemo-naïve
patients with an EGFR mutation (Poster P3.02b-061).
ABOUT ABOUND
ABOUND is a multi-phase, open-label, multicenter clinical trial program
evaluating the use of ABRAXANE in combination with carboplatin or other
novel agents, including immunotherapy, as first- or second-line
treatment of patients with advanced non-small cell lung cancer (NSCLC).
The ABOUND trials included patients 70 years and older, as well as those
with poorer performance status or squamous disease and those receiving
second-line+ treatment.vii,viii,ix,x
ABOUT THE ABRAXANE/NIVOLUMAB STUDY
This is a phase I, open-label, multicenter, safety study of
ABRAXANE-based chemotherapy regimens administered prior to and/or in
combination with nivolumab in pancreatic cancer, NSCLC and metastatic
breast cancer. This is a six arm study assessing two treatment arms per
tumor-type/indication.
About ABRAXANE® (nab-paclitaxel)
ABRAXANE® is indicated for the first-line
treatment of locally advanced or metastatic non–small cell lung cancer,
in combination with carboplatin, in patients who are not candidates for
curative surgery or radiation therapy.
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 <1500cells/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 47% of patients with non–small cell lung
cancer (NSCLC)
-
Monitor for myelotoxicity by performing complete blood cell counts
frequently, including prior to dosing on Days 1, 8, and 15
-
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 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
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
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 NSCLC, the starting dose should be reduced for patients with
moderate or severe hepatic impairment
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
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
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
-
Myelosuppression, peripheral neuropathy, and arthralgia were more
frequent in patients =65 years of age treated with ABRAXANE and
carboplatin in NSCLC
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
-
Reduce starting dose in NSCLC patients with moderate to severe hepatic
impairment
-
Dose reductions or discontinuation may be needed based on severe
hematologic or neurologic 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,
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and YouTube.
Forward-Looking Statements
This press release contains forward-looking statements, which are
generally statements that are not historical facts. Forward-looking
statements can be identified by the words "expects," "anticipates,"
"believes," "intends," "estimates," "plans," "will," "outlook" and
similar expressions. Forward-looking statements are based on
management's current plans, estimates, assumptions and projections, and
speak only as of the date they are made. We undertake no obligation to
update any forward-looking statement in light of new information or
future events, except as otherwise required by law. Forward-looking
statements involve inherent risks and uncertainties, most of which are
difficult to predict and are generally beyond our control. Actual
results or outcomes may differ materially from those implied by the
forward-looking statements as a result of the impact of a number of
factors, many of which are discussed in more detail in our Annual Report
on Form 10-K and our other reports filed with the Securities and
Exchange Commission.
i Langer C, et al. Safety and Efficacy Results from
ABOUND.70+: nab-Paclitaxel + Carboplatin in Elderly Patients with
Advanced NSCLC. Abstract 4630. Presented at the 2016 World Conference of
Lung Cancer (WCLC), December 4-7, 2016.
ii McCleod M, et al. Interim Results from ABOUND.sqm: Safety
of nab-Paclitaxel + Carboplatin Induction Therapy in Squamous Non-Small
Cell Lung Cancer. Abstract 4391. Presented at the 2016 World Conference
of Lung Cancer (WCLC), December 4-7, 2016.
iii Socinsky M, et al. Safety and efficacy of weekly nab®-paclitaxel
in combination with carboplatin as first-line therapy in elderly
patients with advanced non-small-cell lung cancer. Annals of Oncology.
24: 314–321, 2013.
iv Weiss J, et al. ABOUND.70+: Interim Quality of Life
Results of nab-Paclitaxel + Carboplatin Treatment of Elderly
Patients with NSCLC. Abstract 4286. Presented at the 2016 World
Conference of Lung Cancer (WCLC), December 4-7, 2016.
v Thomas M, et al. nab-Paclitaxel + Carboplatin Induction
Therapy in Squamous Non-Small Cell Lung Cancer: Interim Quality of Life
Results from ABOUND.sqm. Abstract 4343. Presented at the 2016 World
Conference of Lung Cancer (WCLC), December 4-7, 2016.
vi Goldman J, et al. Interim Results from the Phase I Study
of Nivolumab + nab-Paclitaxel + Carboplatin in Non-Small Cell Lung
Cancer. Abstract 4127. Presented at the 2016 World Conference of Lung
Cancer (WCLC), December 4-7, 2016.
vii ClinicalTrials.gov. Safety and Efficacy Study of Nab®Paclitaxel
With CC486 or Nab®Paclitaxel With Durvalumab, and Nab®Paclitaxel
Monotherapy as Second/Thirdline Treatment for Advanced Nonsmall Cell
Lung Cancer (abound2L+). Available at https://www.clinicaltrials.gov/ct2/show/NCT02250326?term=ABOUNd&rank=3.
Accessed November 30, 2016.
viii ClinicalTrials.gov. Safety and Efficacy Study of
Abraxane in Combination With Carboplatin to Treat Advanced NSCL Cancer
in the Elderly (ABOUND 70+). Available at https://www.clinicaltrials.gov/ct2/show/NCT02151149?term=ABOUNd&rank=2.
Accessed November 30, 2016.
ix ClinicalTrials.gov. Phase II Safety and Tolerability Trial
With NabPaclitaxel Plus Carboplatin Followed by NabPaclitaxel for First
Line Treatment of NSCLC Subjects With ECOG PS 2 (AboundPS2). Available
at https://www.clinicaltrials.gov/ct2/show/NCT02289456?term=ABOUNd&rank=4.
Accessed November 30, 2016.
x ClinicalTrials.gov. Safety and Efficacy Study of Abraxane
as Maintenance Treatment After Abraxane Plus Carboplatin in 1st Line
Stage IIIB / IV Squamous Cell Non-small Cell Lung Cancer (aboundsqm).
Available at https://www.clinicaltrials.gov/ct2/show/NCT02027428?term=ABOUNd&rank=6.
Accessed November 30, 2016.