NORTHBROOK, Ill. and
SAN FRANCISCO, Jan. 26, 2016 /PRNewswire/ -- Astellas US
LLC, a United States (U.S.)
subsidiary of Tokyo-based Astellas
Pharma Inc. (TSE: 4503), and Medivation, Inc. (Nasdaq: MDVN) today
announced that results from the STRIVE trial of enzalutamide
compared to bicalutamide in men with castration-resistant prostate
cancer (CRPC) were published in the Journal of Clinical
Oncology. The article, titled, "Enzalutamide Versus
Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE
Trial," appears in the January 25,
2016 online issue and will be published in a future print
issue of the journal.
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, 0.18-0.32; p<0.0001). Median PFS
was 19.4 months in the enzalutamide group compared with 5.7 months
in the bicalutamide group.
The median time on treatment in the STRIVE trial was 14.7 months
in the enzalutamide group versus 8.4 months in the bicalutamide
group. Serious adverse events were reported in 29.4% of
enzalutamide-treated patients and 28.3% of bicalutamide-treated
patients. Grade 3 or higher cardiac adverse events were
reported in 5.1% of enzalutamide-treated patients versus 4.0% of
bicalutamide-treated patients. One seizure was reported in the
trial in the enzalutamide-treated group and none in the
bicalutamide-treated 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.
The STRIVE study is the second of two head-to-head studies of
enzalutamide versus bicalutamide, the first of which was TERRAIN,
which was published in the January 13,
2016 online issue of Lancet Oncology.
About the STRIVE Trial
The Phase 2 STRIVE trial enrolled 396 castration-resistant
prostate cancer patients in the U.S. 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 PFS, defined as time from randomization
to radiographic (bone or soft tissue) progression,
prostate-specific antigen (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 (n=198)
versus bicalutamide at a dose of 50 mg taken once daily (n=198),
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 blocks
multiple steps in the androgen receptor signaling pathway within
the tumor cell. In preclinical studies, enzalutamide has been shown
to competitively inhibit androgen binding to androgen receptors,
and inhibit androgen receptor nuclear translocation and interaction
with DNA.
Important Safety Information
Contraindications XTANDI is not indicated for women and
is contraindicated in women who are or may become pregnant. XTANDI
can cause fetal harm when administered to a pregnant woman.
Warnings and Precautions
Seizure In Study 1, conducted in patients with metastatic
castration-resistant prostate cancer (CRPC) who previously received
docetaxel, seizure occurred in 0.9% of XTANDI patients and 0% of
placebo patients. In Study 2, conducted in patients with
chemotherapy-naive metastatic CRPC, seizure occurred in 0.1% of
XTANDI patients and 0.1% of placebo patients. There is no clinical
trial experience re- administering XTANDI to patients who
experienced a seizure, and limited safety data are available in
patients with predisposing factors for seizure. Study 1 excluded
the use of concomitant medications that may lower threshold; 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.
Posterior Reversible Encephalopathy Syndrome (PRES) In
post approval use, there have been reports of PRES in patients
receiving XTANDI. PRES is a neurological disorder which can present
with rapidly evolving symptoms including seizure, headache,
lethargy, confusion, blindness, and other visual and neurological
disturbances, with or without associated hypertension. A diagnosis
of PRES requires confirmation by brain imaging, preferably MRI.
Discontinue XTANDI in patients who develop PRES.
Adverse Reactions
The most common adverse reactions (≥ 10%) reported from two
combined clinical studies that occurred more commonly (≥ 2% over
placebo) in XTANDI 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.
In Study 1, Grade 3 and higher adverse reactions were reported
among 47% of XTANDI patients and 53% of placebo patients.
Discontinuations due to adverse events were reported for 16% of
XTANDI patients and 18% of placebo patients. In Study 2, Grade 3-4
adverse reactions were reported in 44% of XTANDI patients and 37%
of placebo patients. Discontinuations due to adverse events were
reported for 6% of both study groups.
- Lab Abnormalities: Grade 1-4 neutropenia occurred in 15% of
XTANDI patients (1% Grade 3-4) and 6% of placebo patients (0.5%
Grade 3-4). Grade 1-4 thrombocytopenia occurred in 6% of XTANDI
patients (0.3% Grade 3-4) and 5% of placebo patients (0.5% Grade
3-4). Grade 1-4 elevations in ALT occurred in 10% of XTANDI
patients (0.2% Grade 3-4) and 16% of placebo patients (0.2% Grade
3-4). Grade 1-4 elevations in bilirubin occurred in 3% of XTANDI
patients (0.1% Grade 3-4) and 2% of placebo patients (no Grade
3-4).
- Infections: In Study 1, 1% of XTANDI patients compared to 0.3%
of placebo patients died from infections or sepsis. In Study 2, 1
patient in each treatment group (0.1%) had an infection resulting
in death.
- Falls (including fall-related injuries), occurred in 9% of
XTANDI patients and 4% of placebo patients. 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 occurred in 11% of XTANDI patients and 4% of
placebo patients. No patients experienced hypertensive crisis.
Medical history of hypertension was balanced between arms.
Hypertension led to study discontinuation in < 1% of all
patients.
Drug Interactions
Effect of Other Drugs on XTANDI Avoid strong CYP2C8
inhibitors, as they can increase the plasma exposure to XTANDI. If
co-administration is necessary, reduce the dose of XTANDI.
Avoid strong CYP3A4 inducers as they can decrease the plasma
exposure to XTANDI. If co-administration is necessary, increase the
dose of XTANDI.
Effect of XTANDI on Other Drugs 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
http://www.astellas.us/docs/us/12A005-ENZ-WPI.pdf?v=1
You are encouraged to report negative side effects of
prescription drugs to the FDA.
Visit www.fda.gov/medwatch or call
1800FDA1088.
About Medivation Inc.
Medivation, Inc. is a biopharmaceutical company focused on the
development and commercialization 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
http://www.medivation.com
About Astellas
Astellas is a pharmaceutical company dedicated to improving the
health of people around the world through provision of innovative
and reliable pharmaceuticals. For more information on Astellas,
please visit our website at www.astellas.us, follow us on
Twitter at www.twitter.com/AstellasUS or like our
Facebook page at www.facebook.com/AstellasUS.
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.
Logo - http://photos.prnewswire.com/prnh/20140416/84970
To view the original version on PR Newswire,
visit:http://www.prnewswire.com/news-releases/journal-of-clinical-oncology-publishes-results-from-the-strive-trial-of-enzalutamide-compared-to-bicalutamide-in-castration-resistant-prostate-cancer-300210093.html
SOURCE Astellas Pharma Inc.