Phase II tnAcity Trial found a significantly
longer Progression Free Survival with ABRAXANE + carboplatin
compared to ABRAXANE + gemcitabine or carboplatin + gemcitabine
regimens
Celgene Corporation (NASDAQ:CELG) today announced that the
results of its randomized phase II tnAcity trial of ABRAXANE® for
injectable suspension (paclitaxel protein-bound particles for
injectable suspension) (albumin-bound) will be presented at the
2016 San Antonio Breast Cancer Symposium (SABCS) December 6-10,
2016. The trial found that an investigational weekly combination
regimen of ABRAXANE + carboplatin had significantly longer
progression-free survival (PFS) (7.4 months) compared to weekly
regimens of either ABRAXANE + gemcitabine (5.4 months) or of
carboplatin + gemcitabine (6.0 months) as first-line treatment of
patients with metastatic triple-negative breast cancer
(mTNBC).i
The phase II trial randomized 191 women with mTNBC to receive
one of three weekly regimens (dosed 2 out of 3 weeks): ABRAXANE +
carboplatin, ABRAXANE + gemcitabine, or carboplatin + gemcitabine
as first-line treatment. The study findings demonstrated that
ABRAXANE + carboplatin resulted in significantly longer PFS (7.4
months) than combination regimens with ABRAXANE + gemcitabine (5.4
months; P=0.02, HR 0.60 (95% CI, 0.39-0.93)) or carboplatin +
gemcitabine (6.0 months; P= 0.03, HR 0.61 (95% CI, 0.39-0.94)).
tnAcity also found that those treated with the ABRAXANE +
carboplatin regimen experienced a longer median treatment duration
(25 weeks) than those treated with ABRAXANE + gemcitabine (18.1
weeks) or carboplatin + gemcitabine (20.1 weeks).i
The most common grade ≥3 treatment emergent adverse events
(TEAEs) observed in the ABRAXANE + carboplatin, ABRAXANE +
gemcitabine, and carboplatin + gemcitabine arms, respectively,
during the study were mainly hematologic and included neutropenia
(42%, 27%, 52%), anemia (13%, 12%, 27%), thrombocytopenia (9%, 7%,
28%), leukopenia (6%, 3%, 11%), febrile neutropenia (5%, 2%, 0%),
peripheral neuropathy (5%, 7%, 2%) and fatigue (3%, 15%, 3%). A
median of 8 treatment cycles were initiated for the ABRAXANE +
carboplatin arm and 6 cycles for both the ABRAXANE + gemcitabine
and carboplatin + gemcitabine arms. The percentage of patients that
discontinued any study drug due to a TEAE was 45% for ABRAXANE +
carboplatin and 25% for each of the other arms. The most common AEs
leading to discontinuation of any study drug included
thrombocytopenia, anemia, neutropenia and drug
hypersensitivity.i
“Metastatic triple negative breast cancer is one of the most
challenging types of cancers for treating physicians and patients
alike, and there remains an important unmet need in these patients
to find more effective treatment options,” said Dr. Denise A.
Yardley, Senior Investigator, Breast Cancer Research Program;
Principal Investigator, Sarah Canon Research Institute. “These data
add to the body of knowledge about ABRAXANE in metastatic triple
negative breast cancer, a disease that requires additional
research.”
After taking into consideration the rapidly changing breast
cancer treatment landscape, which has a significant focus on
immuno-oncology treatments, Celgene had determined not to move
forward with the phase III portion of tnAcity. The Company will
instead focus its breast cancer research support on
ABRAXANE/Immunotherapy combinations and remains committed to
applying the findings of tnAcity to ongoing and future research of
ABRAXANE in breast cancer for patients with high unmet needs.
“The findings of tnAcity are encouraging, illustrating that an
ABRAXANE-containing regimen may have activity in a type of breast
cancer with few viable treatments and these findings give
researchers additional insight into how to treat metastatic triple
negative breast cancer,” said Michael Pehl, President, Hematology
and Oncology for Celgene. “Celgene is committed to continuing to
support research in breast cancer to identify regimens for patients
with aggressive disease and in areas with limited treatment
options.”
ABRAXANE is not indicated for the first-line treatment of
metastatic breast cancer, or for the treatment regimens studied in
tnAcity.
ABOUT tnAcityi,ii
tnAcity is a phase II/III multicenter, open-label, randomized
clinical trial conducted in 139 centers in 12 countries. The study
evaluated the safety and efficacy of the investigational use of a
weekly treatment regimen of ABRAXANE in combination with
carboplatin or gemcitabine as a first-line treatment of women with
metastatic triple negative breast cancer (mTNBC) compared to a
gemcitabine + carboplatin regimen.ii
The phase II portion of the tnAcity trial evaluated 191 patients
with metastatic triple negative breast cancer (mTNBC) who had
received no prior systemic chemotherapy treatment for their mTNBC
and had an ECOG performance status of 0 or 1. Patients were
randomized to one of three treatment arms: ABRAXANE 125 mg/m2 +
carboplatin AUC 2, ABRAXANE 125 mg/m2 + gemcitabine 1000 mg/m2, or
carboplatin AUC 2 + gemcitabine 1000 mg/m2 dosed weekly on days 1
and 8 of a 21-day cycle. The median age in each treatment arm was
55 (ABRAXANE + carboplatin), 53 (ABRAXANE + gemcitabine) and 59
(carboplatin + gemcitabine) years. The primary endpoint of the
phase II trial was investigator assessed progression free survival
(PFS). Secondary endpoints evaluated in the study included overall
survival (OS) and objective response rate (ORR).
Additional ABRAXANE Data Presented at
SABCS
Additional investigator initiated studies presented at SABCS
also evaluated the investigational uses of ABRAXANE in the
neoadjuvant setting in patients with previously untreated breast
cancer (GeparSepto; P5-16-03) and as induction and
maintenance therapy for women with HER2-negative metastatic breast
cancer (SNAP; P5-15-05).
ABOUT ABRAXANE
ABRAXANE® for Injectable Suspension (paclitaxel
protein-bound particles for injectable suspension) (albumin-bound)
is indicated 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.
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
CONTRADINDICATIONS
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
34% of patients with metastatic breast cancer (MBC)
- Monitor for myelotoxicity by performing
complete blood cell counts frequently, including prior to dosing on
Day 1
- Do not administer ABRAXANE to patients
with baseline absolute neutrophil counts (ANC) of less than 1,500
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 MBC
- Resume treatment with every-3-week
cycles of ABRAXANE after ANC recovers to a level > 1500
cells/mm3 and platelets recover to > 100,000 cells/mm3
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 until resolution to Grade 1 or 2 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 MBC, 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
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
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 to 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
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 MBC 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.
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.
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 Yardley D, et al. nab-Paclitaxel + Carboplatin or Gemcitabine
vs Gemcitabine + Carboplatin as First-Line Treatment for Patients
With Triple-Negative Metastatic Breast Cancer: Results From the
Randomized Phase II Portion of the tnAcity Trial. Poster 874.
Presented at the 2016 San Antonio Breast Cancer Symposium (SABCS),
December 6-10, 2016.
ii Clinicaltrials.gov. Evaluate Risk/Benefit of Nab Paclitaxel
in Combination With Gemcitabine and Carboplatin Compared to
Gemcitabine and Carboplatin in Triple Negative Metastatic Breast
Cancer (or Metastatic Triple Negative Breast Cancer) (tnAcity).
Available at:
https://www.clinicaltrials.gov/ct2/show/NCT01881230?term=tnacity&rank=1.
Accessed November 29, 2016.
View source
version on businesswire.com: http://www.businesswire.com/news/home/20161207005287/en/
Celgene
CorporationInvestors:908-673-9628investors@celgene.comorMedia:908-673-2275media@celgene.com
Celgene (NASDAQ:CELG)
Historical Stock Chart
From Mar 2024 to Apr 2024
Celgene (NASDAQ:CELG)
Historical Stock Chart
From Apr 2023 to Apr 2024