LONDON, March 24, 2015 /PRNewswire/ --
Astellas Pharma Europe Ltd. today
announced new data from the Phase 2 TERRAIN trial of enzalutamide
compared to bicalutamide in metastatic castration-resistant
prostate cancer (CRPC), as well as an updated overall survival
analysis from the placebo-controlled Phase 3 PREVAIL trial of
enzalutamide in chemotherapy-naive metastatic CRPC. The data were
presented during a plenary session at the 2015 European Association
of Urology (EAU) Congress in Madrid,
Spain.
(Logo:
http://photos.prnewswire.com/prnh/20140522/689211 )
"The late breaking data presented at this year's EAU Congress
further demonstrate the breadth and depth of the enzalutamide
development programme," said Claire
Thom, Pharm.D., Senior Vice President and Oncology
Therapeutic Head, Astellas Pharma Global Development, Inc. "We are
encouraged to see that enzalutamide continues to generate promising
data for men with advanced prostate cancer and their loved
ones."
Highlights of Key Enzalutamide Data
Title: A randomized,
double-blind, Phase 2,
efficacy and safety study of enzalutamide
vs. bicalutamide
in metastatic castrate resistant prostate cancer:
TERRAIN trial[1]
The Phase 2 TERRAIN trial enrolled 375 patients in North America and Europe. The trial enrolled patients with
metastatic prostate cancer whose disease progressed despite
treatment with a luteinising hormone-releasing hormone (LHRH)
analogue therapy or following surgical castration. The primary
endpoint of the trial was progression-free survival (PFS), defined
as time from randomisation to centrally confirmed radiographic
progression, skeletal related event, initiation of new
anti-neoplastic therapy or death, whichever occurred first. The
trial was designed to evaluate enzalutamide at a dose of 160 mg
taken orally once daily versus bicalutamide at a dose of 50 mg
taken once daily, the approved dose in combination with a LHRH
analogue.
"The results of the TERRAIN trial, if confirmed, have the
potential to impact the treatment landscape of metastatic
castration-resistant prostate cancer," said Axel Heidenreich, M.D., Ph.D., Professor and
Director, Department of Urology, University hospital, Aachen,
Germany. "The study demonstrated
an improvement with enzalutamide over the standard practice of
the addition of bicalutamide to a luteinising hormone-releasing
hormone (LHRH) therapy."
- The study achieved its primary objective of a statistically
significant increase in PFS for enzalutamide compared to
bicalutamide. The median PFS in the enzalutamide arm was 9.9 months
longer compared to that in the bicalutamide arm (15.7 vs 5.8
months, respectively) with a Hazard Ratio (HR) of 0.44 (95%
confidence interval, 0.34-0.57; p<0.0001);
- The median time to PSA progression was 13.6 months longer with
enzalutamide (19.4 months) relative to bicalutamide treatment (5.8
months) with a HR of 0.28 (p<0.0001);
- 82% of enzalutamide-treated patients achieved ≥ 50% PSA
reduction from baseline by week 13 vs 21% of bicalutamide-treated
patients;
- The median time on enzalutamide treatment was 11.7 months
compared to 5.8 months on bicalutamide;
- The safety profile of the enzalutamide-treated patients in
TERRAIN is consistent with the known safety profile of
enzalutamide.
- Serious adverse events (AEs) were reported in 31.1% of
enzalutamide vs 23.3% bicalutamide patients and Grade 3 or higher
cardiac AEs were observed in 5.5% of enzalutamide vs 2.1% of
bicalutamide patients. Two seizures were reported with enzalutamide
and 1 with bicalutamide;
- The common (≥10%) AEs reported more frequently with
enzalutamide vs bicalutamide were fatigue (27.9% vs 20.1%), back
pain (19.1% vs 18.0%), hot flush (14.8% vs 11.1%), hypertension
(14.2% vs 7.4%), diarrhea (11.5% vs 9.0%), weight decreased (10.9%
vs 7.9%) and pain in extremities (10.9% vs 5.3%).
Title: Enzalutamide in men with
chemotherapy-naïve
metastatic castration-resistant prostate cancer
(mCRPC): Final overall survival analysis of
the Phase 3 PREVAIL
study[2]
The Phase 3 PREVAIL trial, a randomised, double-blind,
placebo-controlled, multi-national trial, enrolled 1,717 patients
at sites in the United States,
Canada, Europe, Australia, Russia, Israel and Asia, including Japan. The trial enrolled patients with
chemotherapy-naïve metastatic prostate cancer whose disease
progressed on androgen deprivation therapy (i.e., a LHRH therapy or
after bilateral orchiectomy). The co-primary endpoints of the trial
were overall survival and radiographic progression-free survival.
The trial was designed to evaluate enzalutamide at a dose of 160 mg
taken orally once daily versus placebo.
"The most interesting observations around these data are that
enzalutamide achieved significant overall survival despite many
patients receiving additional treatment, and that the diagnosis of
when a patient's disease becomes metastatic, which drives the
timing of therapy initiation, is important," said Bertrand Tombal, M.D., Ph.D., Professor and
Chairman, Department of Urology, Universite catholique de Louvain,
Cliniques universitaires Saint-Luc, Brussels. "The standard approach, as done in
the placebo arm of PREVAIL, is to wait usually for some symptoms or
rapid radiological progression before initiating chemotherapy.
However, this study demonstrated that starting patients on
enzalutamide at the point when their castration-resistant prostate
cancer becomes metastatic has the potential to prolong
survival."
- An updated overall survival analysis was conducted at 784
deaths and found a statistically significant overall survival
benefit with a 23% reduction in risk of death (OS: HR 0.77; 95% CI
0.67-0.88; P=0.0002) and a 4-month improvement in median survival
with enzalutamide (35.3 months [95% CI 32.2-not yet reached]) over
placebo (31.3 months [95% CI 28.8-34.2]). As of the June 2014 cut-off date with a median follow-up
duration of 31 months:
- 52% of enzalutamide and 81% of placebo patients received ≥1
subsequent life-extending prostate cancer therapy.
About
XTANDI™ (enzalutamide)
Enzalutamide is a novel, oral, once-daily androgen receptor
signaling inhibitor. Enzalutamide directly targets the androgen
receptors (AR) and exerts its effects on all three steps of AR
signaling pathway:
- Blocks androgen binding[3]
- Androgen binding induces a conformational change that triggers
activation of the receptor[4]
- Prevents nuclear
translocation[3]
- Transit of the AR to the nucleus is an essential step in
AR-mediated gene
regulation[4]
- Impairs DNA binding[3]
- Binding of the AR to the DNA is essential for modulation of
gene expression[4]
Enzalutamide was first approved by the European Commission in
June 2013 for the treatment of adult
men with mCRPC whose disease has progressed on or after docetaxel
therapy.[5] Enzalutamide is now approved in Europe for the treatment of adult men with
metastatic castration-resistant prostate cancer who are
asymptomatic or mildly symptomatic after failure of androgen
deprivation therapy in whom chemotherapy is not yet clinically
indicated.[5]
Important Safety Information for
XTANDI™ (enzalutamide)
For important Safety Information for enzalutamide please see the
full Summary of Product Characteristics at:
http://www.medicines.org.uk/emc/medicine/27912/SPC/Xtandi+40mg+soft+capsules/.
About Astellas
Astellas Pharma Europe Ltd. operates in 40 countries across
Europe, the Middle East and Africa, and is the regional business of
Tokyo-based Astellas Pharma Inc.
Astellas is a pharmaceutical company dedicated to improving the
health of people around the world through the provision of
innovative and reliable pharmaceuticals. The organisation's focus
is to deliver outstanding R&D and marketing to continue growing
in the world pharmaceutical market. Astellas' presence in
Europe also includes an R&D
site and three manufacturing plants. The company employs
approximately 4,350 staff across these countries. For more
information about Astellas Pharma Europe Ltd., please visit
http://www.astellas.eu.
About the Medivation/Astellas Collaboration
In October 2009, Medivation
(NASDAQ: MDVN) and Astellas (TSE: 4503) entered into a global
agreement to jointly develop and commercialise enzalutamide. The
companies are collaborating on a comprehensive development program
that includes studies to develop enzalutamide across the full
spectrum of advanced prostate cancer as well as advanced breast
cancer. The companies jointly commercialise XTANDI in the United States and Astellas has
responsibility for manufacturing and all additional regulatory
filings globally, as well as commercialising XTANDI outside
the United States.
References
1. A randomized, double-blind, phase 2, efficacy and safety
study of enzalutamide vs. bicalutamide in metastatic castrate
resistant prostate cancer: TERRAIN trial. Abstract presented at EAU
2015
2. Enzalutamide in men with chemotherapy-naïve metastatic
castration-resistant prostate cancer (mCRPC): Final overall
survival analysis of the phase 3 PREVAIL study. Abstract presented
at EAU 2015
3. Tran C, et al. Development of a second-generation
antiandrogen for treatment of advanced prostate cancer. Science
2009; 324:787-790
4. Hu R, Denmeade SR and Luo J. Molecular processes leading to
aberrant androgen receptor signaling and castration resistance in
prostate cancer. Expert Rev Endocrinol Metab 2010; 5 (5):
753-764
5. European Medicines Agency. XTANDI (enzalutamide). Summary of
Product Characteristics, 2015