Interim Data from a Randomized, Head-to-Head Phase II Study Shows Weekly ABRAXANE Increased Tumor Response Rate by Greater Than 60 Percent versus Taxotere in First-Line Treatment of Metastatic Breast Cancer
Abraxis BioScience, Inc. (NASDAQ:ABBI), an integrated, global
biopharmaceutical company, today presented data in an oral
presentation at the 29th Annual San Antonio Breast Cancer Symposium
(SABCS) from an interim analysis of a randomized, head-to-head Phase
II trial of ABRAXANE(R) for Injectable Suspension (paclitaxel
protein-bound particles for injectable suspension) (albumin bound)
versus Taxotere(R) (docetaxel) Injection Concentrate, in the
first-line treatment of metastatic breast cancer. The interim analysis
showed that first-line treatment with weekly ABRAXANE (100 and 150
mg/m(2)) increased tumor response rate by greater than 60 percent with
less toxicity versus Taxotere (100 mg/m(2)) given every three weeks in
patients with metastatic breast cancer. The interim analysis also
showed that weekly ABRAXANE nearly doubled the response rate with less
toxicity compared to ABRAXANE (300 mg/m(2)) dosed every three weeks.
Although the data are not fully mature, the interim analysis showed
that all three ABRAXANE regimens currently have longer
progression-free survivals than Taxotere dosed every three weeks. A
blinded, independent radiological review of the response data is in
process and the company intends to submit the final analysis of the
data to the American Society of Clinical Oncology (ASCO) in 2007.
Based on these encouraging data, Abraxis plans to initiate a
worldwide head-to-head Phase III registration trial comparing weekly
ABRAXANE to every three week Taxotere for the treatment of first-line
metastatic breast cancer. The Phase III registration trial is expected
to begin in the first half of 2007 in multiple sites throughout North
America, Eastern and Western Europe, and Asia-Pacific.
"These interim data show that weekly ABRAXANE, when used in the
first-line treatment of patients with metastatic breast cancer,
increased the response rate by over 60 percent with less toxicity than
the FDA-approved dose of Taxotere given every three weeks," said
William Gradishar, M.D., F.A.C.P, Director, Breast Medical Oncology at
Robert H. Lurie Comprehensive Cancer Center Northwestern University, a
lead investigator in the study. "These data are consistent with
previous study results of both ABRAXANE and Taxotere, and are very
encouraging for both physicians and patients."
"The high response rate to weekly ABRAXANE observed in this study
is consistent with other data presented at this symposium by the NSABP
Foundation Research Group and the International Oncology Network, and
provides new insight into the clinical development of ABRAXANE," said
Michael Hawkins, M.D., chief medical officer of Abraxis BioScience.
"The Phase II results provide the direction needed to initiate a Phase
III trial examining weekly ABRAXANE versus Taxotere in first-line
treatment of metastatic breast cancer. We look forward to presenting
the final analysis of this Phase II study next year."
About the Study
In the randomized Phase II study more than 300 patients with stage
4 metastatic breast cancer and no prior chemotherapy treatments
received one of four treatment regimens: ABRAXANE 300 mg/m(2) (n= 76)
dosed every three weeks, ABRAXANE 100 mg/m(2) (n= 76) or 150 mg/m(2)
(n= 74) dosed weekly for three weeks out of four, and Taxotere 100
mg/m(2) (n= 76) dosed every three weeks. The purpose of the study was
to obtain comparative toxicity and preliminary anti-tumor response
data addressing three issues:
-- ABRAXANE versus Taxotere;
-- Weekly versus every three week dosing of ABRAXANE; and
-- A high and low dose of ABRAXANE.
The secondary endpoint of the study was progression-free survival.
Data from this trial were intended to provide direction for the design
of future trials with ABRAXANE.
The prospectively planned interim analysis demonstrated that
first-line treatment with ABRAXANE 100 or 150 mg/m(2) weekly compared
to Taxotere resulted in a statistically significant increase in
response rates of 61 percent (58% vs. 36%, p=.004) and 72 percent (62%
vs. 36%, p=.0016), respectively. Both weekly dose regimens of ABRAXANE
also increased the response rate compared to every three week ABRAXANE
(58% and 62% vs. 33%; p less than 0.001). Although these data are not
mature with only 33 percent of potential events having occurred, in
the current analysis, all three ABRAXANE treatment arms have longer
progression-free survivals compared to Taxotere (by log rank).
Compared to Taxotere, all three ABRAXANE treatment arms (300
mg/m(2) q3w, 100 mg/m(2) wkly, 150 mg/m(2) wkly) demonstrated less
frequent adverse events with regard to:
-- Grade 4 Neutropenia (74% Taxotere vs. 4%, 3%, 7% ABRAXANE,
respectively);
-- Febrile neutropenia (7% Taxotere vs. 1%, 1%, 1% ABRAXANE,
respectively); and
-- Grade 1/2 Mucositis/stomatitis (20% Taxotere vs. 3%, 1%, 0%
ABRAXANE, respectively).
There was no grade 4 peripheral neuropathy reported in any of the
treatment arms. There were no statistical differences in peripheral
neuropathy between the ABRAXANE regimens compared to Taxotere.
In this study, ABRAXANE (100 mg/m2 wkly) demonstrated a better
therapeutic index as compared to the other two regimens of ABRAXANE
and Taxotere, demonstrating a response rate of 58 percent versus 36
percent for Taxotere with improvement in the adverse event profile.
There was no statistical difference in arthralgias between ABRAXANE
100 mg/m2 compared to Taxotere. Fatigue was significantly lower in
ABRAXANE 100 mg/m2 compared to Taxotere (21% vs. 46%, p < 0.001).
ABRAXANE 100 mg/m2 weekly compared to the other two ABRAXANE treatment
arms (300 mg/ m2 q3w, 150 mg/m2 wkly) resulted in less peripheral
neuropathy (37% vs. 51% and 47%, respectively), arthralgias (16% vs.
33% and 35%, respectively), and fatigue (21% vs. 33% and 39%,
respectively). The only adverse event occurring at a greater frequency
with ABRAXANE (300 mg/m2 q3w and 150 mg/m2 wkly) compared to Taxotere
was arthralgia (33% and 35% vs. 16%, respectively, p