Data comparing ABRAXANE to Taxol, both in combination with
carboplatin, to be revealed during late-breaking presentation at the 46th
Annual Meeting of the American Society of Clinical Oncology
LOS ANGELES, Jun 05, 2010 (BUSINESS WIRE) --Abraxis BioScience, Inc. (NASDAQ:ABII) announced today that findings
from their phase 3 randomized trial of nanoparticle albumin
bound (nab(R)) driven chemotherapy, nab-paclitaxel
(ABRAXANE(R) for Injectable Suspension; paclitaxel albumin
protein-bound particles for injectable suspension) plus carboplatin,
showed a statistically significant 31 percent improvement in overall
response rate (ORR) when compared with Taxol(R) (paclitaxel)
injection plus carboplatin in the first-line treatment of patients with
non-small cell lung cancer (NSCLC). Patients in the ABRAXANE arm
demonstrated an ORR of 33 percent compared with those receiving Taxol,
with an ORR of 25 percent, as assessed by independent radiologic review
using RECIST criteria. This difference met statistical significance at
p=0.005 and achieved the primary end point agreed to with the FDA in a
Special Protocol Assessment. In addition, analysis of the highly
difficult-to-treat subset of squamous cell carcinoma, showed a 67
percent improvement (p<0.001) in those who received the ABRAXANE
combination versus those who received the Taxol combination. Results
from this randomized registrational trial (Abstract # LBA7511) will be
presented for the first time as a late-breaker during an oral session on
June 7 at the 46th Annual Meeting of the American Society of
Clinical Oncology (ASCO) in Chicago (6:30 PM EDT E Hall D2).
Typical first-line chemotherapy treatment used in patients with NSCLC is
paclitaxel in combination with platinum. Platinum-based doublet therapy
in NSCLC has reached a therapeutic plateau, producing a 15-25 percent
ORR, regardless of the combination used.1,2,3 The activity of
ABRAXANE, with a 33 percent ORR, is postulated to be as a result of
targeting an albumin-specific receptor (gp60), thereby activating a
process known as transcytosis to create a path through the proliferating
blood vessel wall allowing the administered drugs to reach the tumor
cells in higher concentration. This hypothesis is the subject of ongoing
pre-clinical and clinical research.
In this phase 3 study, 1,052patients with histologically or
cytologically confirmed stage IIIB or IV NSCLC who had not received
prior treatment for metastatic disease were randomized 1:1 to receive
six cycles of carboplatin AUC 6 on day one of a three-week treatment
cycle in combination with either nab-paclitaxel (100 mg/m2)
weekly or solvent-based paclitaxel (200 mg/m2) every three
weeks until disease progression or unacceptable toxicity.
"The results of this phase 3 study confirmed that the nab-paclitaxel
and carboplatin combination demonstrated a response to treatment that is
superior to a current standard of care in advanced non-small cell lung
cancer," said Mark Socinski, M.D., principal investigator, University of
North Carolina Lineberger Comprehensive Cancer Center. "This is an
important finding as we continue to look for new treatment options for
lung cancer patients, especially those in late stage."
"These lung cancer trial results support the efficacy of ABRAXANE in
advanced and difficult-to-treat cancers," said Patrick Soon-Shiong,
M.D., Executive Chairman and founder of Abraxis BioScience. "Of
particular interest to us, ABRAXANE was highly active in the squamous
cell subset, which may be related to the aberrant caveolin-1
over-expression in squamous cell carcinoma. We are extremely pleased by
the results of this trial, and look forward to continued advancements in
the treatment of this devastating disease."
This trial is the subject of a Special Protocol Assessment with the FDA,
which means that the agency has previously agreed to study design,
clinical endpoints and statistical analyses. Specifically, the FDA has
stipulated that demonstrating statistically superior response rate of
the nab-paclitaxel and carboplatin combination over the
paclitaxel and carboplatin combination with an acceptable safety profile
would be sufficient to submit a supplemental new drug application (sNDA)
(as a 505(b)(2) submission) for approval of nab-paclitaxel in
combination with carboplatin for the first-line treatment of NSCLC.
Difficult-to-treat, NSCLC accounts for approximately 85 percent of all
lung cancer cases. The American Cancer Society (ACS) estimates that
approximately 219,440 people will be diagnosed with lung cancer in the
United States in 2009, and that approximately 159,000 deaths occur each
year due to this cancer.4
About the Study
Results of a Randomized, Phase 3 Trial of nab-Paclitaxel (nab-P)
and Carboplatin (C) Compared With Cremophor-based Paclitaxel (P) and
Carboplatin as First-line Therapy in Advanced Non-small Cell Lung Cancer
(NSCLC) (Abstract #LBA7511)
In this phase 3 study, 1,052 patients with advanced NSCLC were treated.
Patients were diagnosed with histologically or cytologically confirmed
stage IIIB or IV NSCLC, had not received prior treatment for metastatic
disease and had an Eastern Cooperative Oncology Group Performance Status
Scale (ECOG PS) of 0-1. Patients were randomized 1:1 to a treatment
regimen that consisted of six cycles of carboplatin AUC 6 on day 1 of a
three-week treatment cycle in combination with either nab-paclitaxel
(100 mg/m2) weekly or cremophor-based paclitaxel (200 mg/m2)
every three weeks until disease progression or unacceptable toxicity.
The primary endpoint for this study was disease response, measured as CR
and PR as defined by RECIST criteria. The secondary endpoint was
progression-free survival (PFS).
An independent radiologist review showed nab-paclitaxel was
well-tolerated and provided a significant improvement in overall
response rate as compared with Taxol, both administered in combination
with carboplatin. PR or CR was demonstrated in 170 patients (33 percent)
receiving the nab-paclitaxel combination versus demonstrated
response in 132 patients (25 percent) (p=0.005) treated with the
paclitaxel combination. Histologic analysis showed significantly
improved ORR for nab-paclitaxel versus paclitaxel in squamous
cell carcinoma patients (41 percent versus 24 percent, p<.001), a 67
percent improvement, and comparative effectiveness in patients with
non-squamous histology (ORR of 26 percent versus 25 percent
The safety results were generally consistent with the known safety
profile of nab-paclitaxel. The most common grade 3 and 4 adverse
events that occurred were neutropenia (45 percent), anemia (27 percent),
leucopenia (22 percent) and thrompocytopenia (17 percent). Of particular
note, there was significantly less sensory neuropothy in the nab-paclitaxel
versus the paclitaxel (3 percent versus 10 percent, p<.001). Other grade
3 and 4 adverse events observed included myalgia, anorexia, nausea,
fatigue, and alopecia. There were no cases of grade 3 or 4 arthralgia.
About nab(R)-Driven Chemotherapy
Abraxis BioScience has developed a proprietary nanoparticle
albumin-bound (nab) technology which
leverages albumin nanoparticles for the active and targeted delivery of
chemotherapeutics to the tumor. This nab-driven chemotherapy
provides a new paradigm for penetrating the blood-stroma barrier to
reach the tumor cell. The proposed mechanism of delivery of this nab-driven
chemotherapy is thought to be by targeting a previously unrecognized
tumor-activated, albumin-specific biologic pathway with a nanoshell of
the human blood protein albumin. This nano-shuttle system is believed to
activate an albumin-specific (Gp60) receptor-mediated transcytosis path
through the cell wall of proliferating tumor cells, using caveolin-1
activated caveolar transport. Once in the stromal micro-environment, the
albumin-bound drug may be preferentially localized by a second
albumin-specific binding protein, SPARC, a protein secreted into the
stroma by tumor cells. The resulting collapse of stroma surrounding the
tumor cell may thus enhance the delivery of the nab-chemotherapeutic
to the intracellular core of the tumor cell itself.
ABRAXANE is the first clinical validation of the nanoparticle albumin
bound (nab) technology platform and is a treatment option for
metastatic breast cancer. This protein-bound chemotherapy agent combines
paclitaxel with albumin, a naturally-occurring human blood protein.
ABRAXANE is currently in various stages of investigation for the
treatment of the following cancers: expanded applications for metastatic
breast, non-small cell lung, malignant melanoma, pancreatic and gastric.
The U.S. Food and Drug Administration approved ABRAXANE for Injectable
Suspension (paclitaxel protein albumin-bound particles for injectable
suspension) (albumin-bound) in January 2005 for the treatment of breast
cancer after failure of combination chemotherapy for metastatic disease
or relapse within six months of adjuvant chemotherapy. Prior therapy
should have included an anthracycline unless clinically contraindicated.
For the full prescribing information for ABRAXANE please visit http://www.abraxane.com.
IMPORTANT SAFETY INFORMATION
The use of ABRAXANE has not been studied in patients with hepatic or
renal dysfunction. In the randomized controlled trial, patients were
excluded for baseline serum bilirubin >1.5 mg/dL or baseline serum
creatinine >2 mg/dL.
ABRAXANE can cause fetal harm when administered to a pregnant woman.
Women of childbearing potential should be advised to avoid becoming
pregnant while receiving treatment with ABRAXANE.
Men should be advised to not father a child while receiving treatment
It is recommended that nursing be discontinued when receiving ABRAXANE
therapy. ABRAXANE contains albumin (human), a derivative of human blood.
Caution should be exercised when administering ABRAXANE concomitantly
with known substrates or inhibitors of CYP2C8 and CYP3A4.
ABRAXANE therapy should not be administered to patients with metastatic
breast cancer who have baseline neutrophil counts of less than 1,500
cells/mm3. It is recommended that frequent peripheral blood cell counts
be performed on all patients receiving ABRAXANE. Patients should not be
retreated with subsequent cycles of ABRAXANE until neutrophils recover
to a level >1,500 cells/mm3 and platelets recover to a level >100,000
cells/mm3. In the case of severe neutropenia (<500 cells/mm3 for 7 days
or more) during a course of ABRAXANE therapy, a dose reduction for
subsequent courses is recommended. Sensory neuropathy occurs frequently
If grade 3 sensory neuropathy develops, treatment should be withheld
until resolution to grade 1 or 2 followed by a dose reduction for all
subsequent courses of ABRAXANE. Severe cardiovascular events possibly
related to single-agent ABRAXANE occurred in approximately 3% of
patients in the randomized trial. These events included chest pain,
cardiac arrest, supraventricular tachycardia, edema, thrombosis,
pulmonary thromboembolism, pulmonary embolism, and hypertension.
In the randomized metastatic breast cancer study, the most important
adverse events included alopecia (90%), neutropenia (all cases 80%;
severe 9%), sensory neuropathy (any symptoms 71%; severe 10%), asthenia
(any 47%; severe 8%), myalgia/arthralgia (any 44%; severe 8%), anemia
(all 33%; severe 1%), infections (24%), nausea (any 30%; severe 3%),
vomiting (any 18%; severe 4%), diarrhea (any 27%; severe <1%), and
mucositis (any 7%; severe <1%).
Other adverse reactions have included ocular/visual disturbances (any
13%; severe 1%), fluid retention (any 10%; severe 0%), hepatic
dysfunction (elevations in bilirubin 7%, alkaline phosphatase 36%, AST
[SGOT] 39%), renal dysfunction (any 11%; severe 1%), thrombocytopenia
(any 2%; severe <1%), hypersensitivity reactions (any 4%; severe 0%),
cardiovascular reactions (severe 3%), and injection site reactions
(<1%). During postmarketing surveillance, rare occurrences of severe
hypersensitivity reactions have been reported with ABRAXANE.
About Abraxis BioScience, Inc.
Abraxis BioScience is a fully integrated global biotechnology company
dedicated to the discovery, development and delivery of next-generation
therapeutics and core technologies that offer patients safer and more
effective treatments for cancer and other critical illnesses. The
company's portfolio includes chemotherapeutic compound (ABRAXANE(R)),
which is based on the company's proprietary tumor targeting technology
known as the nab(R)platform. The first
FDA approved product to use this nab platform, ABRAXANE, was
launched in 2005 for the treatment of metastatic breast cancer and is
now approved in 39 countries. The company continues to expand the nab platform
through a robust clinical program and deep product pipeline. Abraxis
trades on the NASDAQ Global Market under the symbol ABII. For more
information about the company and its products, please visit www.abraxisbio.com.
The statements contained in this press release that are not purely
historical are forwardlooking statements within the meaning of Section
21E of the Securities Exchange Act of 1934, as amended. Forward-looking
statements in this press release include statements regarding our
expectations, beliefs, hopes, goals, intentions, initiatives or
strategies, including statements regarding the clinical development
plan, and the timing and scope of clinical studies and trials, for
ABRAXANE and the global commercialization of ABRAXANE.
Because these forward-looking statements involve risks and
uncertainties, there are important factors that could cause actual
results to differ materially from those in the forwardlooking
statements. These factors include, without limitation, the fact that
results from preclinical studies may not be predictive of results to be
obtained in other pre-clinical studies or future clinical trials; delays
in commencement and completion of clinical studies or trials, including
slower than anticipated patient enrollment and adverse events occurring
during the clinical trials; decisions by regulatory authorities
regarding whether and when to approve ABRAXANE or product candidates for
various indications as well as their decisions regarding labeling and
other matters that could affect the availability or commercial potential
of ABRAXANE and other products and product candidates; unexpected
safety, efficacy or manufacturing issues with respect to ABRAXANE or
product candidates; the need for additional data or clinical studies for
ABRAXANE or product candidates; regulatory developments (domestic or
foreign) involving the company's manufacturing facilities; the market
adoption and demand of ABRAXANE and other products, the costs associated
with the ongoing launch of ABRAXANE; research and development associated
with the nab(R)technology platform; the
impact of pharmaceutical industry regulation; the impact of competitive
products and pricing; the availability and pricing of ingredients used
in the manufacture of pharmaceutical products; the ability to
successfully manufacture products in a time-sensitive and cost effective
manner; the acceptance and demand of new pharmaceutical products; and
the impact of patents and other proprietary rights held by competitors
and other third parties. Additional relevant information
concerning risks can be found in the company's Annual Report on Form
10-K for the year ended December 31, 2009 and in other documents it has
filed with the Securities and Exchange Commission.
The information contained in this press release is as of the date of
this release. Abraxis assumes no obligations to update any
forward-looking statements contained in this press release as the result
of new information or future events or developments.
TAXOL(R) is a registered trademark of Bristol-Myers Squibb Company.
1 Kelly K et al. "Randomized Phase III Trial of Paclitaxel
Plus Carboplatin Versus Vinorelbine Plus Cisplatin in the Treatment of
Patients With Advanced Non-Small-Cell Lung Cancer: A Southwest Oncology
Group Trial." Journal of Clinical Oncology. 2001: Vol 19, No 13
(July 1): pp 3210-3218.
2 Schiller JH et al. "Comparison of Four Chemotherapy
Regimens for Advanced Non-Small-Cell Lung Cancer." The New England
Journal of Medicine. 2002: Vol 346, No. 2 (January 10): pp 92-98.
3 Sandler A et al. "Paclitaxel-Carboplatin Alone or with
Bevacizumab for Non-Small-Cell Lung Cancer." The New England Journal
of Medicine. 2006: Vol 355, No. 24 (December 14): pp 2542-50.
4 Cancer Facts & Figures 2008. American Cancer Society
SOURCE: Abraxis BioScience, Inc.
Abraxis BioScience, Inc.
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