Phase 3 ARCHES Trial Shows XTANDI® (enzalutamide) Significantly Improved Radiographic Progression-Free Survival in Men with Metastatic Hormone-Sensitive Prostate Cancer

Data to be presented at the 2019 Genitourinary Cancers Symposium

NEW YORK & TOKYO–(BUSINESS WIRE)–Pfizer Inc. (NYSE: PFE) and Astellas Pharma Inc. (TSE: 4503, President
and CEO: Kenji Yasukawa, Ph.D., “Astellas”) announced today results from
the Phase 3 ARCHES trial in men with metastatic hormone-sensitive
prostate cancer (mHSPC). Prostate cancer is considered metastatic once
the cancer has spread outside of the prostate gland to other parts of
the body.1 Men are considered hormone (or castration)
sensitive if their disease still responds to medical or surgical
treatment to lower testosterone levels.2

The results show that XTANDI® (enzalutamide) plus androgen
deprivation therapy (ADT) met the primary endpoint by significantly
reducing the risk of radiographic progression or death by 61% versus ADT
alone (n=1,150; HR=0.39 [95% CI: 0.30-0.50]; p<0.0001). These data will be presented in an oral session at the 2019 Genitourinary Cancers Symposium in San Francisco (Abstract #687; Thursday, February 14th,
1:55 PM PT).

“The ARCHES trial demonstrated that XTANDI plus standard hormonal
therapy delayed disease progression, and if approved, has the potential
to be an important treatment option for men with prostate cancer that
has spread but has not yet become hormone resistant,” said Andrew
Armstrong, M.D., Professor of Medicine, Surgery, Pharmacology and Cancer
Biology, and Director of Research in the Duke Cancer Institute’s Center
for Prostate and Urologic Cancers.

Median time to a radiographic progression-free survival (rPFS) event was
not reached in the XTANDI plus ADT arm, while median time to an rPFS
event in the ADT alone arm was 19.4 months. Significant improvements in
rPFS were also observed in all prespecified subgroups including disease
volume, pattern of disease localization at baseline, geographic region,
and prior docetaxel use (HRs=0.24-0.53). Secondary endpoints reported in
the abstract showed that XTANDI plus ADT reduced the risk of PSA
progression (HR=0.19 [95% CI: 0.13-0.26]; p<0.0001) and reduced the risk of starting a new antineoplastic therapy (HR=0.28 [95% CI: 0.20-0.40]; p<0.0001) compared to ADT alone. Undetectable PSA and objective response rates were also higher in men treated with XTANDI plus ADT versus ADT alone (68.1% versus 17.6%; p<0.0001 and 83.1% versus 63.7%; p<0.0001, respectively). Treatment with XTANDI plus ADT did not significantly reduce the risk of deterioration in urinary symptoms compared to ADT alone. At the time of the analysis, overall survival (OS) data were not mature.

Adverse events (AEs) in the ARCHES clinical trial were generally
consistent with those reported in enzalutamide clinical trials in
patients with castration-resistant prostate cancer (CRPC). Grade 3 or 4
AEs were reported in 23.6 percent of men receiving XTANDI plus ADT
versus 24.7 percent of men receiving ADT alone. Common AEs (occurring in
at least 5 percent of patients) that were reported more often in
patients treated with XTANDI plus ADT versus those treated with ADT
alone included hot flush, fatigue, arthralgia, hypertension, nausea,
musculoskeletal pain, diarrhea, asthenia and dizziness.

Based on the ARCHES results, the companies intend to discuss these data
with global health authorities to potentially support a new indication
for XTANDI in men with mHSPC. XTANDI is currently approved in the U.S.
and Japan for the treatment of CRPC and in the EU for the treatment of
metastatic and high-risk non-metastatic CRPC.

Seven additional abstracts evaluating XTANDI will also be presented at
the 2019 Genitourinary Cancers Symposium.


The Phase 3, randomized, double-blind, placebo-controlled,
multi-national trial enrolled 1,150 patients with metastatic
hormone-sensitive prostate cancer (mHSPC) at sites in the United States,
Canada, Europe, South America and the Asia-Pacific region. Patients in
the ARCHES trial were randomized to receive XTANDI 160 mg daily or
placebo and continued on a luteinizing hormone-releasing hormone (LHRH)
agonist or antagonist or had a history of bilateral orchiectomy. The
ARCHES trial included patients with both low- and high-volume disease
and both newly diagnosed patients with mHSPC and patients who had prior
definitive therapy and subsequently developed metastatic disease. The
trial also included some patients who had received recent treatment with
docetaxel for mHSPC, but whose disease had not progressed. The primary
endpoint of the trial was radiographic progression-free survival (rPFS),
defined as the time from randomization to the first objective evidence
of radiographic disease progression as assessed by central review, or
death within 24 weeks of treatment discontinuation. For more information
on the ARCHES (NCT02677896)
trial, go to

About Metastatic Hormone-Sensitive Prostate Cancer

In men with prostate cancer, the disease is considered metastatic once
the cancer has spread outside of the prostate gland to other parts of
the body, such as the bones, lymph nodes, bladder and rectum.1
Men are considered hormone (or castration) sensitive if their disease
still responds to medical or surgical treatment to lower testosterone
levels.2 Approximately 38,000 men in the U.S. develop
metastatic HSPC every year.3,4

About XTANDI® (enzalutamide) capsules

XTANDI (enzalutamide) is an androgen receptor inhibitor indicated for
the treatment of patients with castration-resistant prostate cancer.

As part of Pfizer and Astellas’ ongoing commitment to the clinical
development of enzalutamide, XTANDI is also being evaluated in the
EMBARK trial, in men with high-risk non-metastatic HSPC. Details about
EMBARK (NCT02319837)
are available on

Important Safety Information for XTANDI® in

Warnings and Precautions

Seizure occurred in 0.4% of patients receiving XTANDI in
clinical studies. In a study of patients with predisposing factors for
seizure, 2.2% of XTANDI-treated patients experienced a seizure. Patients
in the study had one or more of the following pre-disposing factors: use
of medications that may lower the seizure threshold; history of
traumatic brain or head injury, cerebrovascular accident or transient
ischemic attack, 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. It is unknown whether anti-epileptic medications
will prevent seizures with XTANDI. 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) 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.

Hypersensitivity reactions, including edema of the face (0.5%),
tongue (0.1%), or lip (0.1%) have been observed with XTANDI in 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 placebo-controlled clinical
studies, ischemic heart disease occurred more commonly in patients on
the XTANDI arm compared to patients on the placebo arm (2.7% vs 1.2%).
Grade 3-4 ischemic events occurred in 1.2% of patients on XTANDI versus
0.5% 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 In the placebo-controlled clinical studies,
falls occurred in 10% of patients treated with XTANDI compared to 4% of
patients treated with placebo. Fractures occurred in 8% of patients
treated with XTANDI and in 3% of patients treated with placebo. 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.

Embryo-Fetal Toxicity 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. XTANDI should not be handled by females who are or may become

Adverse Reactions

The most common adverse reactions (≥ 10%) that occurred more frequently
(≥ 2% over placebo) in the XTANDI patients from the randomized
placebo-controlled trials were asthenia/fatigue, decreased appetite, hot
flush, arthralgia, dizziness/vertigo, hypertension, headache and weight
decreased. In the bicalutamide-controlled study, the most common adverse
reactions (≥ 10%) reported in XTANDI patients were asthenia/fatigue,
back pain, musculoskeletal pain, hot flush, hypertension, nausea,
constipation, diarrhea, upper respiratory tract infection, and weight

In the placebo-controlled study of metastatic CRPC (mCRPC) patients
taking XTANDI who previously received docetaxel, 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 the
placebo-controlled study of chemotherapy-naïve mCRPC patients, 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. In the placebo-controlled study of
non-metastatic CRPC (nmCRPC) patients, Grade 3 or higher adverse
reactions were reported in 31% of XTANDI patients and 23% of placebo
patients. Discontinuations with an adverse event as the primary reason
were reported for 9% of XTANDI patients and 6% of placebo patients. In
the bicalutamide-controlled study of chemotherapy-naïve mCRPC patients,
Grade 3-4 adverse reactions 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

Lab Abnormalities: In the two placebo-controlled trials in
patients with mCRPC, Grade 1-4 neutropenia occurred in 15% of XTANDI
patients (1% Grade 3-4) and 6% of placebo patients (0.5% Grade 3-4). In
the placebo-controlled trial in patients with nmCRPC, Grade 1-4
neutropenia occurred in 8% of patients receiving XTANDI (0.5% Grade 3-4)
and in 5% of patients receiving placebo (0.2% Grade 3-4).

Hypertension: In the two placebo-controlled trials in patients
with mCRPC, hypertension was reported in 11% of XTANDI patients and 4%
of placebo patients. Hypertension led to study discontinuation in <1% of patients in each arm. In the placebo-controlled trial in patients with nmCRPC, hypertension was reported in 12% of patients receiving XTANDI and 5% of patients receiving placebo.

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

Please see Full
Prescribing Information
 for additional safety information.

About Pfizer Oncology

At Pfizer Oncology, we are committed to advancing medicines wherever we
believe we can make a meaningful difference on the lives of patients.
Today, Pfizer Oncology has an industry-leading portfolio of 17 approved
innovative cancer medicines and biosimilars across more than 20
indications, including breast, prostate, kidney, lung and hematology. We
also have several assets in mid to late-stage development for the
treatment of cancer or as supportive care. Pfizer Oncology is striving
to change the trajectory of cancer.

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

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 February 11, 2019.
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) and potential new indications being evaluated for the
treatment of men with metastatic hormone-sensitive prostate cancer and
the treatment of men with high-risk non-metastatic hormone-sensitive
prostate cancer, including their 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 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; the risks associated
with interim data; whether and when drug applications for any of the
potential new indications for XTANDI or any potential indications for
XTANDI may be filed in any jurisdictions; whether and when regulatory
authorities in any jurisdictions 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
for any such potential new indications 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, including for the
potential new indications; 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; 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, 2017 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


1 American Society of Clinical Oncology. ASCO Answers:
Prostate Cancer (2018).
Accessed 11-13-2018.

2 Prostate Cancer: Types of Treatment (03-2018).
Accessed 11-7-2018.

3 Scher HI, Solo K, Valant J, Todd MB, Mehra M et al.
Prevalence of Prostate Cancer Clinical States and Mortality in the
United States: Estimates Using a Dynamic Progression Model. PLoS One.
2015; 10(10): 1-2.

4 Siegel RL, Miller KD, Jemal A, Cancer statistics, 2018. CA
Cancer Journal for Clinicians. 2018;68:7–30.


Pfizer Contacts:
For Media
Jessica Smith
[email protected]

For Investors
Ryan Crowe
[email protected]

Astellas Contacts:
For Media
Colin McBean
[email protected]

For Investors
Shin Okubo
[email protected]

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