FDA Approves New Indication for FASLODEX® (fulvestrant)

Approval Expands Use and Offers Additional Option for Women with HR+,
HER2- Metastatic Breast Cancer

WILMINGTON, Del.–(BUSINESS WIRE)–AstraZeneca today announced that the US Food and Drug Administration
(FDA) has approved a new indication expanding the use of FASLODEX®
(fulvestrant) to include use in combination with palbociclib. The
combination use is for the treatment of women with hormone
receptor-positive (HR+), human epidermal growth factor receptor 2
negative (HER2-) advanced or metastatic breast cancer (MBC) whose cancer
has progressed after endocrine therapy.1 FASLODEX has been
approved since 2002 as a monotherapy for the treatment of postmenopausal
women with HR+ MBC whose cancer has progressed following antiestrogen

Estrogen receptor (ER) positive breast cancer is the most common subtype
of breast cancer and one of the key drivers of disease progression for
this subtype is through the ER. Laboratory studies show that FASLODEX
directly targets the ER by blocking and degrading the ER, helping to
inhibit tumor growth.1,2

“The new FASLODEX indication provides another important treatment option
for patients, as described in the study, who progressed on or early
after prior endocrine therapy. The data supporting combination therapy
with FASLODEX plus palbociclib showed a clear increase in
progression-free survival in patients in the combination arm, as
compared to FASLODEX and placebo,” said Dr. Dennis Slamon, Professor of
Medicine, Chief of the Division of Hematology/Oncology and Executive
Vice Chair for Research for UCLA’s Department of Medicine.

The FDA approval of this new indication for FASLODEX is based on data
from the Phase III PALOMA-3 trial, which met the study’s primary
endpoint of progression-free survival (PFS). The combination of FASLODEX
500 mg and palbociclib 125 mg resulted in a 4.9 month PFS improvement
over FASLODEX and placebo, in women with HR+ HER2- advanced or MBC whose
disease had progressed after endocrine therapy. Improvement in PFS was
seen irrespective of menopausal status.1

The most common adverse reactions (≥10%) of any grade reported in
PALOMA-3 of FASLODEX plus palbociclib vs FASLODEX plus placebo included
neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs
31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%),
stomatitis (28% vs 13%), headache (26% vs 20%), diarrhea (24% vs 19%),
thrombocytopenia (23% vs 0%), constipation (20% vs 16%), vomiting (19%
vs 15%), alopecia (18% vs 6%), rash (17% vs 6%), decreased appetite (16%
vs 8%), and pyrexia (13% vs 5%).1 For more information,
please see Important Safety Information for FASLODEX below.

“We believe that advances in cancer treatment will come, in part, from
our research building upon existing treatments. This new indication adds
to the existing body of evidence supporting FASLODEX-based therapy for
certain metastatic breast cancer patients in an area where there is
still a high unmet medical need,” said Andrew Coop, Vice President, US
Medical Affairs, Oncology at AstraZeneca.



FASLODEX is contraindicated in patients with known hypersensitivity to
the drug or to any of its components. Hypersensitivity reactions,
including urticaria and angioedema have been reported in association

Risk of Bleeding

Because FASLODEX is administered intramuscularly, it should be used with
caution in patients with bleeding diatheses, thrombocytopenia, or in
patients on anticoagulants.

Hepatic Impairment

FASLODEX is metabolized primarily in the liver. A 250-mg dose is
recommended in patients with moderate hepatic impairment (Child-Pugh
class B). FASLODEX has not been evaluated in patients with severe
hepatic impairment (Child-Pugh class C).

Embryo-Fetal Toxicity and Lactation

Advise pregnant women of the potential risk to a fetus. Advise females
of reproductive potential to use effective contraception during FASLODEX
treatment and for 1 year after the last dose. Advise lactating women not
to breast-feed during treatment with FASLODEX and for 1 year after the
final dose because of the potential risk to the infant.

Adverse Reactions


The most common adverse reactions occurring in ≥5% of patients receiving
500 mg FASLODEX were: injection site pain, nausea, bone pain,
arthralgia, headache, back pain, fatigue, pain in extremity, hot flash,
vomiting, anorexia, asthenia, musculoskeletal pain, cough, dyspnea, and

Increased hepatic enzymes (ALT, AST, ALP) occurred in >15% of FASLODEX
users and were not dose-dependent.

Combination Therapy

The most frequently reported serious adverse reactions in patients
receiving FASLODEX plus palbociclib were infections (3%), pyrexia (1%),
neutropenia (1%) and pulmonary embolism (1%). A causal relationship
between these events and FASLODEX alone has not been established.

The most common adverse reactions (≥10%) of any grade reported in
patients receiving FASLODEX plus palbociclib were: neutropenia,
leukopenia, infections, fatigue, nausea, anemia, stomatitis, headache,
diarrhea, thrombocytopenia, constipation, vomiting, alopecia, rash,
decreased appetite, and pyrexia.

Indications for FASLODEX


FASLODEX is indicated for the treatment of hormone receptor
(HR)-positive metastatic breast cancer in postmenopausal women with
disease progression following antiestrogen therapy.

Combination Therapy

FASLODEX in combination with palbociclib is indicated for the treatment
of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative
advanced or metastatic breast cancer in women with disease progression
after endocrine therapy.

The full Prescribing Information for FASLODEX is available here.


About PALOMA-3

PALOMA-3 is a Phase III international, randomized, double-blind,
parallel group, multicenter study of FASLODEX plus palbociclib versus
FASLODEX plus placebo conducted in women with HR+/HER2- advanced or
metastatic breast cancer, regardless of their menopausal status, whose
disease progressed on or after endocrine therapy. The study evaluated
521 pre/postmenopausal women who were randomized 2:1 to FASLODEX plus
palbociclib or FASLODEX plus placebo. Women, who were either
premenopausal (meaning they had not reached menopause), or
perimenopausal (meaning that their bodies were making the natural
transition toward menopause), were therapeutically induced to become
postmenopausal and represented 20.7% of the study population.1

Patients enrolled in this study had a median age of 57 years (range 29
to 88). The majority of patients in the study were white (74%). All
patients had an ECOG (Eastern Cooperative Oncology Group) PS of 0 or 1,
and 80% were postmenopausal. All patients had received prior systemic
therapy and 75% of patients had received a previous chemotherapy
regimen. Twenty-five percent of patients had received no prior therapy
in the metastatic disease setting, 60% had visceral metastases, and 23%
had bone only disease.1

FASLODEX 500 mg was given as two 5 mL injections, one in each buttock,
on days 1, 15, 29 and once monthly (28 ± 3 days) thereafter. Palbociclib
was given orally at a dose of 125 mg daily for 21 consecutive days
followed by 7 days off treatment. Patients continued to receive their
assigned treatment until objective disease progression, symptomatic
deterioration, unacceptable toxicity, death, or withdrawal of consent,
whichever occurred first.1

About Metastatic Breast Cancer (MBC)

MBC is the most advanced stage of breast cancer (stage four), and occurs
when cancer cells have spread beyond the initial tumor site to other
parts of the body outside of the breast. Since there is no cure for
metastatic breast cancer, the goal of current treatment is to delay
disease progression.3

It is estimated that in 2016, there will be approximately 151,000 women
in the US living with MBC, and this number is projected to increase to
approximately 160,000 by the year 2020.4

About FASLODEX® (fulvestrant)

FASLODEX is approved for the treatment of postmenopausal women with HR+
MBC with disease progression following antiestrogen therapy. FASLODEX is
also indicated for use in combination with palbociclib for the treatment
of women with HR+, HER2- advanced or MBC whose disease progressed after
endocrine therapy.1

FASLODEX represents a hormonal therapy approach that targets the ER. The
ER is a key driver of disease progression. FASLODEX helps to slow tumor
growth by blocking and degrading the ER.1,2

About AstraZeneca in Oncology

AstraZeneca has a deep-rooted heritage in Oncology and offers a quickly
growing portfolio of new medicines that has the potential to transform
patients’ lives and the Company’s future. With at least six new
medicines to be launched between 2014 and 2020 and a broad pipeline of
small molecules and biologics in development, we are committed to
advance Oncology as one of AstraZeneca’s six Growth Platforms focused on
lung, ovarian, breast and blood cancers. In addition to our core
capabilities, we actively pursue innovative partnerships and investments
that accelerate the delivery of our strategy, as illustrated by our
investment in Acerta Pharma in hematology.

By harnessing the power of four scientific platforms – immuno-oncology,
the genetic drivers of cancer and resistance, DNA damage repair and
antibody drug conjugates – and by championing the development of
personalized combinations, AstraZeneca has the vision to redefine cancer
treatment and one day eliminate cancer as a cause of death.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business
that focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of diseases in three
main therapy areas – respiratory, inflammation, autoimmune disease
(RIA), cardiovascular and metabolic disease (CVMD) and oncology – as
well as in infection and neuroscience. AstraZeneca operates in over 100
countries and its innovative medicines are used by millions of patients
worldwide. For more information please visit www.astrazeneca-us.com.



      1.   Prescribing Information for FASLODEX. AstraZeneca Pharmaceuticals
LP, Wilmington, DE.

Howell A. Is fulvestrant (“Faslodex”) just another selective
estrogen receptor modulator? Int J Gynecol Cancer. 2006;16
(suppl 2):521-523.


National Cancer Institute. What Is Cancer?: Metastatic Cancer. Available
. Last accessed 2/11/2016.


CancerMPaact.Khapps.com. Breast-United States (Active
Disease/Stage IV). Updated November 30, 2015. Available
. Last accessed 3/2/2016.


©2016 AstraZeneca. All rights reserved.

3203500 Last Updated 3/16


Abigail Bozarth, +1 302-885-2677