TOKYO and SAN FRANCISCO, May 17,
2015 /PRNewswire/ -- Astellas Pharma Inc (TSE:4503) and
Medivation, Inc (NASDAQ: MDVN) today announced data from the Phase
2 STRIVE trial comparing enzalutamide and bicalutamide in
non-metastatic (M0) and metastatic (M1) prostate cancer patients
whose disease progressed despite treatment with a luteinizing
hormone-releasing hormone (LHRH) analogue therapy or following
surgical castration. The data were presented during an oral plenary
session at the 2015 American Urological Association (AUA) annual
meeting in New Orleans,
Louisiana.
Highlights of Key Enzalutamide Data
Title: A multicenter phase 2 study of enzalutamide
versus bicalutamide in men with nonmetastatic or metastatic
castration-resistant prostate cancer: STRIVE
trial
- The study achieved its primary endpoint demonstrating a
statistically significant increase in progression-free survival
(PFS) for enzalutamide compared with bicalutamide (Hazard Ratio =
0.24; 95% confidence Interval (CI), 0.18-0.32; p<0.0001). The
median PFS was 19.4 months in the enzalutamide arm and 5.7 months
in the bicalutamide arm;
- Treatment with enzalutamide also demonstrated significant
improvement in the secondary endpoints of radiographic PFS, time to
PSA progression, and PSA response rates compared to
bicalutamide;
- For the subset of patients with M0 disease, at the time of the
analysis the median PFS had not yet been reached for patients in
the enzalutamide arm and was 8.6 months in the bicalutamide arm
with a Hazard Ratio (HR) of 0.24 (95% CI, 0.14-0.42; p<0.0001).
For patients with M1 disease, the median PFS was 16.5 months in the
enzalutamide arm and 5.5 months in the bicalutamide arm with a HR
of 0.24 (95% CI, 0.17-0.34; p<0.0001).
- The safety profile of enzalutamide-treated patients in STRIVE
was consistent with the known safety profile of enzalutamide:
- The median duration of treatment was 14.7 months with
enzalutamide and 8.4 months with bicalutamide.
- Serious adverse events (AEs) were reported in 29.4% of
enzalutamide-treated patients and 28.3% of bicalutamide-treated
patients. Grade 3 or higher cardiac AEs were reported in 5.1%
of enzalutamide-treated patients versus 4.0% of
bicalutamide-treated patients. One seizure was reported in the
enzalutamide group and none in the bicalutamide group;
- The most common side effects noted more frequently in the
enzalutamide-treated versus bicalutamide-treated patients included
fatigue, back pain, hot flush, fall, hypertension, dizziness and
decreased appetite, consistent with the known safety profile of
enzalutamide.
"Results from the STRIVE trial are of key interest to the
medical community as they mark the second head-to-head trial of
enzalutamide versus bicalutamide," said Celestia S. Higano, M.D., FACP, co-principal
investigator of the STRIVE trial and professor, medicine and
urology, University of Washington. "The
analyses from STRIVE are in line with previous data from the
TERRAIN trial demonstrating that patients treated with enzalutamide
have improved clinical outcomes versus the common practice of
adding bicalutamide to a luteinizing hormone-releasing hormone
therapy."
About the STRIVE Trial
The Phase 2 STRIVE trial
enrolled 396 castration-resistant prostate cancer patients in
the United States. The trial
randomized 257 patients with metastatic prostate cancer and 139
patients with non-metastatic prostate cancer whose disease
progressed despite treatment with a luteinizing hormone-releasing
hormone (LHRH) analogue therapy or following surgical castration.
The primary endpoint of the trial was progression-free
survival, defined as time from randomization to radiographic (bone
or soft tissue) progression, PSA progression (defined by Prostate
Cancer Working Group 2 criteria), or death due to any cause,
whichever occurs first. The trial was designed to evaluate
enzalutamide at a dose of 160 mg taken once daily versus
bicalutamide at a dose of 50 mg taken once daily, the approved dose
in combination with a LHRH analogue.
About XTANDI® (enzalutamide) capsules
XTANDI is approved by the U.S. Food and Drug Administration for the
treatment of patients with metastatic castration-resistant prostate
cancer (CRPC).
Enzalutamide Mechanism of Action
Enzalutamide is an androgen receptor inhibitor that acts on three
different steps in the androgen receptor signaling pathway.
Important Safety Information
Contraindications: XTANDI (enzalutamide) capsules can
cause fetal harm when administered to a pregnant woman based on its
mechanism of action and findings in animals. XTANDI is not
indicated for use in women. XTANDI is contraindicated in women who
are or may become pregnant.
Warnings and Precautions: In Study 1, conducted in
patients with metastatic castration-resistant prostate cancer
(CRPC) who previously received docetaxel, seizure occurred in 0.9%
of patients who were treated with XTANDI and 0% treated with
placebo. In Study 2, conducted in patients with chemotherapy-naïve
metastatic CRPC, seizure occurred in 0.1% of patients who were
treated with XTANDI and 0.1% treated with placebo. Patients
experiencing a seizure were permanently discontinued from therapy
and all seizure events resolved. There is no clinical trial
experience re-administering XTANDI to patients who experienced a
seizure, and limited clinical trial experience in patients with
predisposing factors for seizure. Study 1 excluded the use of
concomitant medications that may lower threshold, whereas Study 2
permitted the use of these medications. Because of the risk of
seizure associated with XTANDI use, patients should be advised of
the risk of engaging in any activity during which sudden loss of
consciousness could cause serious harm to themselves or others.
Permanently discontinue XTANDI in patients who develop a seizure
during treatment.
Adverse Reactions: The most common adverse
reactions (≥ 10%) reported from the two combined clinical trials
that occurred more commonly (≥ 2% over placebo) in the
XTANDI-treated patients were asthenia/fatigue, back pain, decreased
appetite, constipation, arthralgia, diarrhea, hot flush, upper
respiratory tract infection, peripheral edema, dyspnea,
musculoskeletal pain, weight decreased, headache, hypertension, and
dizziness/vertigo.
Other Adverse Reactions include:
- Laboratory Abnormalities: In the two studies, Grade 14
neutropenia occurred in 15% of patients treated with XTANDI (1%
Grade 3-4) and in 6% of patients treated with placebo (0.5% Grade
3-4). The incidence of Grade 14 thrombocytopenia was 6% of patients
treated with XTANDI (0.3% Grade 3-4) and 5% of patients on placebo
(0.5% Grade 3-4). Grade 1-4 elevations in ALT occurred in 10% of
patients treated with XTANDI (0.2% Grade 3-4) and 16% of patients
treated with placebo (0.2% Grade 3-4). Grade 1-4 elevations in
bilirubin occurred in 3% of patients treated with XTANDI (0.1%
Grade 3-4) and 2% of patients treated with placebo (no Grade
3-4).
- Infections: In Study 1, 1% of XTANDI versus 0.3% of placebo
patients and in Study 2, 1 patient in each treatment group (0.1%)
had an infection resulting in death.
- Falls: In the two studies, falls including fall-related
injuries occurred in 9% of XTANDI patients vs 4% treated with
placebo. Falls were not associated with loss of consciousness or
seizure. Fall-related injuries were more severe in XTANDI patients
and included non-pathologic fractures, joint injuries, and
hematomas.
- Hypertension: In the two studies, hypertension was reported in
11% of patients receiving XTANDI and 4% of patients receiving
placebo. No patients experienced hypertensive crisis. Medical
history of hypertension was balanced between arms. Hypertension led
to study discontinuation in < 1% of XTANDI or placebo treated
patients.
Drug Interactions:
- Effect of Other Drugs on XTANDI: Administration of strong
CYP2C8 inhibitors can increase the plasma exposure to XTANDI.
Co-administration of XTANDI with strong CYP2C8 inhibitors should be
avoided if possible. If co-administration of XTANDI cannot be
avoided, reduce the dose of XTANDI. Co-administration of XTANDI
with strong or moderate CYP3A4 and CYP2C8 inducers may alter the
plasma exposure of XTANDI and should be avoided if possible.
- Effect of XTANDI on Other Drugs: XTANDI is a strong CYP3A4
inducer and a moderate CYP2C9 and CYP2C19 inducer in humans. Avoid
CYP3A4, CYP2C9 and CYP2C19 substrates with a narrow therapeutic
index, as XTANDI may decrease the plasma exposures of these drugs.
If XTANDI is co-administered with warfarin (CYP2C9 substrate),
conduct additional INR monitoring.
For Full Prescribing Information for XTANDI (enzalutamide)
capsules, please visit www.XtandiHCP.com
You are encouraged to report negative side effects of
prescription drugs to the FDA. Visit
www.fda.gov/medwatch or call
1800FDA1088.
About Astellas Pharma Inc.
Astellas Pharma Inc. is a
pharmaceutical company dedicated to improving the health of people
around the world through provision of innovative and reliable
pharmaceuticals. The organization is committed to being a global
category leader in Oncology and Urology, and has several oncology
compounds in development in addition to enzalutamide. For more
information on Astellas Pharma Inc., please visit our website at
www.astellas.com/en.
About Medivation, Inc.
Medivation, Inc. is a
biopharmaceutical company focused on the rapid development of
medically innovative therapies to treat serious diseases for which
there are limited treatment options. Medivation aims to transform
the treatment of these diseases and offer hope to critically ill
patients and their families. For more information, please visit us
at www.medivation.com.
About the Medivation/Astellas Collaboration
In
October 2009, Medivation (NASDAQ:
MDVN) and Astellas (TSE: 4503) entered into a global agreement to
jointly develop and commercialize 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 commercialize XTANDI in the United States and Astellas has
responsibility for manufacturing and all additional regulatory
filings globally, as well as commercializing XTANDI outside
the United States.
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