NEW YORK and TOKYO, May 29,
2020 /PRNewswire/ -- Pfizer Inc. (NYSE: PFE) and
Astellas Pharma Inc. (TSE: 4503, President and CEO: Kenji Yasukawa, Ph.D., "Astellas") have
announced final results from the overall survival (OS) analysis of
the Phase 3 PROSPER trial, which evaluated XTANDI®
(enzalutamide) plus androgen deprivation therapy (ADT) versus
placebo plus ADT in men with non-metastatic castration-resistant
prostate cancer (nmCRPC). In the trial, XTANDI plus ADT reduced the
risk of death by 27% (n=1,401; hazard ratio [HR]=0.73; [95%
confidence interval [CI]: 0.61-0.89]; p=0.001) compared to placebo
plus ADT. The median OS was 67.0 months (95% CI: 64.0 to not
reached) for men who received XTANDI plus ADT compared to 56.3
months (95% CI: 54.4 to 63.0) with placebo plus ADT. OS was a key
secondary endpoint of the trial.
These data were simultaneously published online in the New
England Journal of Medicine and presented during the virtual
scientific program of the 2020 American Society of Clinical
Oncology (ASCO) Annual Meeting (Abstract #5515).
"Overall survival is a critical endpoint in evaluating a
prostate cancer medicine," said Cora N.
Sternberg, M.D., F.A.C.P., Clinical Director, Englander
Institute for Precision Medicine and Professor of Medicine in
Hematology & Oncology, Weill Cornell Medicine and
NewYork-Presbyterian. "These results add to the body of evidence
supporting XTANDI's potential to reduce the risk of death in men
with castration-resistant prostate cancer."
In findings published in the New England Journal of
Medicine in 2018, the PROSPER trial met its primary
endpoint of metastasis-free survival (MFS), demonstrating a
significant reduction in the risk of developing metastasis or death
with XTANDI plus ADT compared to ADT alone in men with nmCRPC
(HR=0.29 [95% CI: 0.24-0.35]; p<0.001). MFS was measured as
the time from patients entering the trial until their cancer was
radiographically detected as having metastasized, or until death,
within 112 days of treatment discontinuation.
The safety profile observed in the final OS analysis was
consistent with the 2018 primary analysis and the established
safety profile of enzalutamide. The most common adverse reactions
irrespective of relationship to study drug that occurred more
frequently (≥10%) in XTANDI plus ADT-treated patients in the
PROSPER OS analysis were fatigue (37% vs 16%), hypertension (17% vs
6%), asthenia (10% vs 7%), back pain (13% vs 8%), dizziness (12% vs
6%), diarrhea (12% vs 10%), nausea (13% vs 9%), hot flush (14% vs
8%), fall (18% vs 5%), arthralgia (13% vs 8%), constipation (13% vs
8%), hematuria (10% vs 9%), headache (11% vs 5%) and decreased
appetite (12% vs 5%). In this analysis of the PROSPER trial, Grade
3 or higher adverse reactions were reported in 48% of men treated
with XTANDI plus ADT and in 27% of men treated with placebo plus
ADT.
About Non-Metastatic Castration-Resistant Prostate
Cancer
Castration-resistant prostate cancer (CRPC) refers to
the subset of men whose prostate cancer progresses on androgen
deprivation therapy (ADT) despite castrate levels of testosterone
(i.e., less than 50 ng/dL).1 Non-metastatic CRPC means
there is no clinically detectable evidence of the cancer spreading
to other parts of the body (metastases), and there is a rising
prostate-specific antigen (PSA) level.2 Many men with
non-metastatic CRPC and a rapidly rising PSA level go on to develop
metastatic CRPC.3
PROSPER Trial
The Phase 3 randomized, double-blind,
placebo-controlled, multi-national trial enrolled 1,401 patients
with nmCRPC at sites in the United
States, Canada,
Europe, South America and the Asia-Pacific region. PROSPER enrolled patients
with prostate cancer that had progressed, based on a rising PSA
level despite ADT, but who had no symptoms and no prior or present
evidence of metastatic disease. Of the total patients enrolled, 933
patients were treated with XTANDI at a dose of 160 mg taken orally
once daily plus ADT and 468 patients were treated with placebo
plus ADT.
The primary endpoint of the PROSPER trial, MFS, was measured as
the time from patients entering the trial until their cancer was
radiographically detected as having metastasized, or until death,
within 112 days of treatment discontinuation. Key secondary
endpoints included OS, time to PSA progression and time to first
use of antineoplastic therapy.
For more information on the PROSPER trial, go to
www.clinicaltrials.gov.
About XTANDI® (enzalutamide)
XTANDI
(enzalutamide) is an androgen receptor inhibitor indicated for the
treatment of patients with castration-resistant prostate cancer
(CRPC) and metastatic castration-sensitive prostate cancer
(mCSPC).
Important Safety Information for XTANDI®
Warnings and Precautions
Seizure occurred in 0.5% of patients receiving XTANDI in
seven randomized clinical trials. In a study of patients with
predisposing factors for seizure, 2.2% of XTANDI-treated patients
experienced a seizure. It is unknown whether anti-epileptic
medications will prevent seizures with XTANDI. Patients in the
study had one or more of the following predisposing factors: use of
medications that may lower the seizure threshold, history of
traumatic brain or head injury, history of cerebrovascular accident
or transient ischemic attack, and Alzheimer's disease, meningioma,
or leptomeningeal disease from prostate cancer, unexplained loss of
consciousness within the last 12 months, history of seizure,
presence of a space occupying lesion of the brain, history of
arteriovenous malformation, or history of brain infection. Advise
patients of the risk of developing a seizure while taking XTANDI
and of engaging in any activity where 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) There have been reports of PRES in patients
receiving XTANDI. PRES is a neurological disorder that 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.
Hypersensitivity reactions, including edema of the
face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with
XTANDI in seven randomized clinical trials. Pharyngeal edema has
been reported in post-marketing cases. Advise patients who
experience any symptoms of hypersensitivity to temporarily
discontinue XTANDI and promptly seek medical care. Permanently
discontinue XTANDI for serious hypersensitivity reactions.
Ischemic Heart Disease In the combined data of four
randomized, placebo-controlled clinical studies, ischemic heart
disease occurred more commonly in patients on the XTANDI arm
compared to patients on the placebo arm (2.9% vs 1.3%). Grade 3-4
ischemic events occurred in 1.4% of patients on XTANDI versus 0.7%
on placebo. Ischemic events led to death in 0.4% of patients on
XTANDI compared to 0.1% on placebo. Monitor for signs and symptoms
of ischemic heart disease. Optimize management of cardiovascular
risk factors, such as hypertension, diabetes, or dyslipidemia.
Discontinue XTANDI for Grade 3-4 ischemic heart disease.
Falls and Fractures occurred in patients receiving
XTANDI. Evaluate patients for fracture and fall risk. Monitor and
manage patients at risk for fractures according to established
treatment guidelines and consider use of bone-targeted agents. In
the combined data of four randomized, placebo-controlled clinical
studies, falls occurred in 11% of patients treated with XTANDI
compared to 4% of patients treated with placebo. Fractures occurred
in 10% of patients treated with XTANDI and in 4% of patients
treated with placebo.
Embryo-Fetal Toxicity The safety and efficacy of
XTANDI have not been established in females. XTANDI can cause fetal
harm and loss of pregnancy when administered to a pregnant female.
Advise males with female partners of reproductive potential to use
effective contraception during treatment with XTANDI and for 3
months after the last dose of XTANDI.
Adverse Reactions (ARs)
In the data from the four
randomized placebo-controlled trials, the most common ARs (≥ 10%)
that occurred more frequently (≥ 2% over placebo) in XTANDI-treated
patients were asthenia/fatigue, back pain, hot flush, constipation,
arthralgia, decreased appetite, diarrhea, and hypertension. In the
bicalutamide-controlled study, the most common ARs (≥ 10%) reported
in XTANDI-treated patients were asthenia/fatigue, back pain,
musculoskeletal pain, hot flush, hypertension, nausea,
constipation, diarrhea, upper respiratory tract infection, and
weight loss.
In AFFIRM, the placebo-controlled study of metastatic CRPC
(mCRPC) patients who previously received docetaxel, Grade 3 and
higher ARs were reported among 47% of XTANDI-treated patients.
Discontinuations due to adverse events (AEs) were reported for 16%
of XTANDI-treated patients. In PREVAIL, the placebo-controlled
study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 44% of XTANDI patients and
37% of placebo patients. Discontinuations due to AEs were reported
for 6% of XTANDI-treated patients. In TERRAIN, the
bicalutamide-controlled study of chemotherapy-naive mCRPC patients,
Grade 3-4 ARs were reported in 39% of
XTANDI patients and 38% of bicalutamide patients. Discontinuations
with an AE as the primary reason were reported for 8% of XTANDI
patients and 6% of bicalutamide patients.
In PROSPER, the placebo-controlled study of non-metastatic CRPC
(nmCRPC) patients, Grade 3 or higher ARs were reported in 31% of
XTANDI patients and 23% of placebo patients. Discontinuations with
an AE as the primary reason were reported for 9% of XTANDI patients
and 6% of placebo patients.
In ARCHES, the placebo-controlled study of metastatic CSPC
(mCSPC) patients, Grade 3 or higher AEs were reported in 24% of
XTANDI-treated patients. Permanent discontinuation due to AEs as
the primary reason was reported in 5% of XTANDI patients and 4% of
placebo patients.
Lab Abnormalities: Lab abnormalities that occurred
in ≥ 5% of patients, and more frequently (> 2%) in the
XTANDI arm compared to placebo in the pooled, randomized,
placebo-controlled studies are neutrophil count decreased, white
blood cell decreased, hyperglycemia, hypermagnesemia, hyponatremia,
and hypercalcemia.
Hypertension: In the combined data from four
randomized placebo-controlled clinical trials, hypertension was
reported in 12% of XTANDI patients and 5% of placebo patients.
Hypertension led to study discontinuation in < 1% of patients in
each arm.
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.
Please see Full Prescribing Information for additional
safety information.
About Astellas
Astellas Pharma Inc., based in
Tokyo, Japan, is a company
dedicated to improving the health of people around the world
through the provision of innovative and reliable pharmaceutical
products. For more information, please visit our website at
https://www.astellas.com/en.
About Pfizer Oncology
At Pfizer Oncology, we are
committed to advancing medicines wherever we believe we can make a
meaningful difference in the lives of patients. Today, Pfizer
Oncology has an industry-leading portfolio of 22 approved
innovative cancer medicines and biosimilars across more than 30
indications, including breast, prostate, kidney and lung cancers,
as well as leukemia and melanoma. Pfizer Oncology is striving to
change the trajectory of cancer.
About the Pfizer/Astellas Collaboration
In
October 2009, Medivation, Inc., which
is now part of Pfizer (NYSE: PFE), and Astellas (TSE: 4503) entered
into a global agreement to jointly develop and commercialize
enzalutamide. 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.
Astellas Forward-Looking Statement
In this press
release, statements made with respect to current plans, estimates,
strategies and beliefs and other statements that are not historical
facts are forward-looking statements about the future performance
of Astellas. These statements are based on management's current
assumptions and beliefs in light of the information currently
available to it and involve known and unknown risks and
uncertainties. A number of factors could cause actual results to
differ materially from those discussed in the forward-looking
statements. Such factors include, but are not limited to: (i)
changes in general economic conditions and in laws and regulations,
relating to pharmaceutical markets, (ii) currency exchange rate
fluctuations, (iii) delays in new product launches, (iv) the
inability of Astellas to market existing and new products
effectively, (v) the inability of Astellas to continue to
effectively research and develop products accepted by customers in
highly competitive markets, and (vi) infringements of Astellas'
intellectual property rights by third parties.
Information about pharmaceutical products (including products
currently in development), which is included in this press release
is not intended to constitute an advertisement or medical
advice.
Pfizer Disclosure Notice
The information contained in
this release is as of May 29, 2020.
Pfizer assumes no obligation to update forward-looking statements
contained in this release as the result of new information or
future events or developments.
This release contains forward-looking information about
XTANDI® (enzalutamide), including its potential
benefits, that involves substantial risks and uncertainties that
could cause actual results to differ materially from those
expressed or implied by such statements. Risks and uncertainties
include, among other things, uncertainties regarding the commercial
success of XTANDI; the uncertainties inherent in research and
development, including the ability to meet anticipated clinical
endpoints, commencement and/or completion dates for our clinical
trials, regulatory submission dates, regulatory approval dates
and/or launch dates, as well as the possibility of unfavorable new
clinical data and further analyses of existing clinical data; the
risk that clinical trial data are subject to differing
interpretations and assessments by regulatory authorities; whether
regulatory authorities will be satisfied with the design of and
results from our clinical studies; whether and when drug
applications for XTANDI may be filed in any other jurisdictions;
whether and when regulatory authorities in any jurisdictions where
applications may be pending or filed may approve any such
applications, which will depend on myriad factors, including making
a determination as to whether the product's benefits outweigh its
known risks and determination of the product's efficacy and, if
approved, whether XTANDI will be commercially successful; decisions
by regulatory authorities impacting labeling, manufacturing
processes, safety and/or other matters that could affect the
availability or commercial potential of XTANDI; risks related to
increasing competitive, reimbursement and economic challenges;
dependence on the efforts and funding by Astellas Pharma Inc. for
the development, manufacturing and commercialization of XTANDI;
uncertainties regarding the impact of COVID-19 on our business,
operations and financial results; and competitive developments.
A further description of risks and uncertainties can be found in
Pfizer's Annual Report on Form 10-K for the fiscal year ended
December 31, 2019 and in its
subsequent reports on Form 10-Q, including in the sections thereof
captioned "Risk Factors" and "Forward-Looking Information and
Factors That May Affect Future Results", as well as in its
subsequent reports on Form 8-K, all of which are filed with the
U.S. Securities and Exchange Commission and available
at www.sec.gov and www.pfizer.com.
1 Kirby M, Hirst C, Crawford ED. Characterising the
castration-resistant prostate cancer population: a systematic
review. Int J Clin Pract 2011;65(11):1180-92.
2 Luo J, Beer T, Graff J. Treatment of
nonmetastatic castration-resistant prostate cancer. Oncology
2016;30(4):336-44.
3 Smith MR, Kabbinavar F, Saad F, et al. Natural
history of rising serum prostate-specific antigen in men with
castrate nonmetastatic prostate cancer. J Clin Oncol
2005;23(13):2918-25.
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