TOKYO and NORTHBROOK, Ill., June
1, 2015 /PRNewswire/ -- Astellas Pharma Inc.
(Tokyo: 4503) announced that data
from a Phase 2 study evaluating the investigational use of
enzalutamide as a single agent for the treatment of advanced
androgen receptor (AR) positive, triple-negative breast cancer
(TNBC) were presented during an oral abstracts session at the 2015
American Society of Clinical Oncology (ASCO) Annual Meeting in
Chicago. The study met its primary
endpoint and the abstract was also selected to be featured in the
upcoming 'Best of ASCO' meetings.
The Phase 2 open label single arm, multicenter trial enrolled
118 women with advanced TNBC in two stages. The primary endpoint of
the trial was clinical benefit rate at 16 weeks (CBR16), defined as
the proportion of women with a complete response (CR), partial
response (PR) or stable disease for at least 16 weeks. Two patient
populations were evaluated in this study: the Evaluable patient
population had at least 10 percent of the cells in their primary
tumor sample test positive for the AR and had at least one follow
up tumor assessment, while the Intent-To-Treat population (ITT)
received at least one dose of enzalutamide and their breast cancer
had any amount of AR immunohistochemistry staining present. 75
patients met the criteria for the Evaluable population and a total
of 118 patients were included in the ITT population. There was no
limit to the number of prior treatments received.
- In the 75 Evaluable patients, CBR16 was achieved in 35% (95%
CI: 24-46) including six CR/PR (8%). Clinical benefit rate at
≥ 24 weeks (CBR24) was achieved in 29% (95% CI: 20-41). The
median progression-free survival (PFS) was 14.7 weeks (95% CI:
8.1-19.3).
- In the ITT population, CBR16 was achieved in 25% (95% CI:
17-33) including seven CR/PR (6%). CBR24 was achieved in 20%
(95% CI: 14-29). Median PFS was 12.6 weeks (95% CI:
8.1-15.7).
Data collected in this study enabled the development of a novel
genomic assay. The diagnostic assay, which was also introduced
during a poster abstract session at ASCO, was assessed for its
ability to identify patients who may benefit from enzalutamide.
Approximately 50 percent of the ITT population were diagnostic
positive and data according to this methodology were as
follows:
- In the ITT, 39% (95% CI: 27-53) of patients with diagnostic
positive AR TNBC achieved CBR16 and 36% achieved CBR24 (95% CI:
24-49), whereas 11% (95% CI: 5-21) of patients with diagnostic
negative AR TNBC achieved CBR16 and only 6% (95% CI: 2-16) achieved
CBR24. mPFS was 16.1 weeks (95% CI: 13.3, 27.4) compared with 8.1
weeks (95% CI: 7.4, 12.6), respectively.
- Diagnostic positive AR TNBC patients treated with enzalutamide
as their first or second line of treatment in the ITT population
demonstrated a median PFS of 40.4 weeks (95% CI: 16.1- not yet
reached) compared with 8.9 weeks (95% CI: 7.3, 15.7) in patients
with diagnostic negative AR TNBC disease.
The most common (reported in ≥10%) related adverse events in the
ITT were fatigue (34%), nausea (25%), decreased appetite (13%),
diarrhea and hot flush (10% each).
Best of ASCO
The 'Best of ASCO' Meetings condense the
most cutting-edge science and education from the world's premier
oncology event, the ASCO Annual Meeting, into a two-day program.
The abstracts chosen for presentation and discussion reflect the
foremost research and strategies in oncology that have the greatest
potential to directly impact patient care.
About the Phase 2 Study
The Phase 2 open label,
single-arm study was initiated in June
2013 and completed enrollment in July
2014. 118 patients were enrolled in 2 Stages at sites in
the United States, Canada and Europe. The primary endpoint
of the trial is clinical benefit rate, defined as the proportion of
patients in the Evaluable population with a best response of
complete response, partial response or stable disease at ≥ 16
weeks. All patients received enzalutamide at a dose of 160 mg to be
taken orally once daily.
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-naive
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 readministering 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.
Coadministration of XTANDI with strong CYP2C8 inhibitors should be
avoided if possible. If coadministration of XTANDI cannot be
avoided, reduce the dose of XTANDI. Coadministration 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 coadministered 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
1-800-FDA-1088.
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.
Forward-Looking Statements
Certain of the statements
in this press release, are forward-looking statements that are made
pursuant to the safe harbor provisions of the federal securities
laws. Forward-looking statements involve risks and
uncertainties that could cause Medivation's actual results to
differ significantly from those projected, including, without
limitation: risks related to the timing, progress and results of
Medivation's clinical trials, including the risk that adverse
clinical trial results could alone or together with other factors
result in the delay or discontinuation of the commercialization of
XTANDI or some or all of Medivation's product development
activities; Medivation's dependence on the efforts of and funding
by Astellas for the development, manufacturing and
commercialization of XTANDI; the risk of unanticipated expenditures
or liabilities; and other risks detailed in Medivation's filings
with the Securities and Exchange Commission, or SEC, including its
quarterly report on Form 10-Q for the quarter ended March 31, 2015, which was filed on May 7, 2015. You are cautioned not to place undue
reliance on the forward-looking statements, which speak only as of
the date of this press release. Medivation disclaims any obligation
or undertaking to update, supplement or revise any forward-looking
statements contained in this press release.
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SOURCE Astellas Pharma Inc.