IBRANCE® (palbociclib) Receives Approval in European Union for the Treatment of Women with HR+/HER2- Metastatic Breast Cancer

NEW YORK–(BUSINESS WIRE)– Pfizer Inc. (NYSE:PFE) today announced that the European Commission (EC)
has approved IBRANCE^® (palbociclib) for the treatment of
women with hormone receptor-positive, human epidermal growth factor
receptor 2-negative (HR+/HER2-) locally advanced or metastatic breast
cancer. The approval is for IBRANCE to be used in combination with an
aromatase inhibitor. The approval also covers the use of IBRANCE in
combination with fulvestrant in women who have received prior endocrine
therapy.

IBRANCE is the first medicine to be approved in Europe that works by
inhibiting cyclin-dependent kinases 4 and 6 (CDK 4/6). It also is the
first new medicine approved for the treatment of women with this type of
metastatic breast cancer in the first-line setting in nearly 10 years.
Women with HR+/HER2- metastatic breast cancer represent about 60 percent
of all metastatic breast cancer cases.¹

“Today’s approval of IBRANCE in the European Union (EU) brings an
innovative and much-needed new treatment option to tens of thousands of
women with HR+/HER2- metastatic breast cancer,” said Andreas Penk, M.D.,
regional president, International Developed Markets, Pfizer Oncology.
“With strong and consistent data in three pivotal clinical studies and
rapid adoption as a standard of care in the U.S., IBRANCE represents a
potential new benchmark for the treatment of HR+/HER2- metastatic breast
cancer in Europe.”

The EC approval is based on a robust submission package including
results from the Phase 2 PALOMA-1 trial in postmenopausal women with
estrogen receptor-positive (ER+)/HER2- metastatic breast cancer who had
not received prior systemic therapy for their advanced disease, the
Phase 3 PALOMA-2 trial in the same population and the Phase 3 PALOMA-3
trial in women with HR+/HER2- metastatic breast cancer who had
progressed on prior endocrine therapy. All three randomized trials
demonstrated that IBRANCE in combination with an endocrine therapy
significantly prolonged progression-free survival (PFS) compared to
endocrine therapy alone or endocrine therapy with placebo.

Breast cancer is the most common invasive cancer among women in Europe,
with more than 464,200 new cases and 131,260 deaths per year.²
Up to 30 percent of women diagnosed with and treated for early breast
cancer will go on to develop metastatic breast cancer,^3,4
which occurs when the cancer spreads beyond the breast to other parts of
the body.⁵ There is no cure for metastatic breast cancer,⁶
and patients are in need of new treatment options that help keep their
cancer from worsening, manage symptoms and help them maintain quality of
life for as long as possible.^3,5

“Palbociclib is an exciting advance in the management of women with
hormone receptor-positive breast cancer. Patients with this type of
breast cancer are usually treated with hormone therapy but many will
progress or relapse – and as a result require chemotherapy, which often
comes with life-limiting side-effects,” said Nicholas Turner, M.D.,
Ph.D., team leader at The Institute of Cancer Research, London, and
consultant medical oncologist at The Royal Marsden NHS Foundation Trust,
as well as principal investigator of the PALOMA-3 trial. “Palbociclib,
when used in combination with standard hormone therapy, increases the
duration of tumor control and is well tolerated by most women – and
could delay the need for women with this type of advanced breast cancer
to start chemotherapy.”

“Metastatic breast cancer patients in Europe need new treatment options
available to them,” said Kathi Apostolidis, two-time breast cancer
survivor and vice president of the European Cancer Patient Coalition.
“Metastatic breast cancer places a heavy burden on cancer patients and
their families, but patients hope that novel treatments may have the
potential to provide better quality of life and outcomes.”

About the IBRANCE Pivotal Trials

PALOMA-1

The Phase 2 PALOMA-1 trial evaluated IBRANCE in combination with
letrozole compared with letrozole alone as a first-line, or initial,
therapy in 165 postmenopausal women with ER+/HER2- advanced breast
cancer who had not received previous systemic treatment for their
advanced disease. The combination of IBRANCE plus letrozole
significantly prolonged PFS compared to letrozole alone (HR=0.488 [95%
CI: 0.319–0.748]), with the median PFS of 20.2 months (95% CI:
13.8–27.5) in the IBRANCE arm compared to 10.2 months (95% CI: 5.7–12.6)
in women who received letrozole alone. The most common adverse events
(≥20%) of any grade reported in patients treated with IBRANCE plus
letrozole versus letrozole alone included neutropenia (75% vs 5%),
leukopenia (43% vs 3%), fatigue (41% vs 23%), anemia (35% vs 7%), upper
respiratory infection (31% vs 18%), nausea (25% vs 13%), stomatitis (25%
vs 7%), alopecia (22% vs 3%) and diarrhea (21% vs 10%).⁷

PALOMA-2

The Phase 3 PALOMA-2 trial evaluated IBRANCE in combination with
letrozole compared with letrozole plus placebo as a first-line treatment
in 666 postmenopausal women with ER+/HER2- metastatic breast cancer, the
same patient population as PALOMA-1. The combination of IBRANCE plus
letrozole resulted in a statistically significant improvement in PFS
(HR=0.58 [95% CI: 0.46–0.72], P<0.000001), with a median PFS of 24.8
months compared to 14.5 months for those who were treated with letrozole
plus placebo. The most common adverse events (≥20%) of any grade
reported in patients treated with IBRANCE plus letrozole versus
letrozole plus placebo included neutropenia (79.5% vs 6.3%), fatigue
(37.4% vs 27.5%), nausea (35.1% vs 26.1%), arthralgia (33.3% vs 33.8%)
and alopecia (32.9% vs 15.8%).⁸

PALOMA-3

The Phase 3 PALOMA-3 trial evaluated IBRANCE in combination with
fulvestrant compared with placebo plus fulvestrant in 521 women with
HR+/HER2- metastatic breast cancer, regardless of menopausal status,
whose disease progressed on or after prior endocrine therapy. The
combination of IBRANCE plus fulvestrant substantially improved PFS
compared to fulvestrant plus placebo (HR=0.461 [95% CI: 0.360–0.591),
P<0.0001), with a median PFS of 9.5 months (95% CI: 9.2–11.0) in the
IBRANCE arm compared to 4.6 months (95% CI: 3.5–5.6) in women who
received placebo plus fulvestrant. The most common adverse events (≥20%)
of any grade reported in PALOMA-3 of IBRANCE plus fulvestrant versus
placebo plus fulvestrant 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%) and
constipation (20% vs 16%).⁷

About IBRANCE^® (palbociclib)

IBRANCE is an oral inhibitor of cyclin-dependent kinases 4 and 6,⁷
which are key regulators of the cell cycle that trigger cellular
progression.^9,10 With this latest regulatory milestone,
IBRANCE now is approved in more than 50 countries.

IBRANCE^® (palbociclib) INDICATIONS AND
IMPORTANT SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

IBRANCE is indicated in the U.S. for the treatment of HR+, HER2-
advanced or metastatic breast cancer in combination with letrozole as
initial endocrine based therapy in postmenopausal women, or fulvestrant
in women with disease progression following endocrine therapy. The
indication in combination with letrozole is approved under accelerated
approval based on PFS. Continued approval for this indication may be
contingent upon verification and description of clinical benefit in a
confirmatory trial.

Neutropenia was the most frequently reported adverse reaction in
PALOMA-1 (75%) and PALOMA-3 (83%). In PALOMA-1, Grade 3 (57%) or 4 (5%)
decreased neutrophil counts were reported in patients receiving IBRANCE
plus letrozole. In PALOMA-3, Grade 3 (56%) or Grade 4 (11%) decreased
neutrophil counts were reported in patients receiving IBRANCE plus
fulvestrant. Febrile neutropenia has been reported in about 1% of
patients exposed to IBRANCE. One death due to neutropenic sepsis was
observed in PALOMA-3. Inform patients to promptly report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning
of each cycle, on Day 14 of first 2 cycles, and as clinically indicated.
Dose interruption, dose reduction, or delay in starting treatment cycles
is recommended for patients who develop Grade 3 or 4 neutropenia.

Pulmonary embolism (PE) has been reported at a higher rate in
patients treated with IBRANCE plus letrozole in PALOMA-1 (5%) and in
patients treated with IBRANCE plus fulvestrant in PALOMA-3 (1%) compared
with no cases in patients treated either with letrozole alone or
fulvestrant plus placebo. Monitor for signs and symptoms of PE and treat
as medically appropriate.

Based on the mechanism of action, IBRANCE can cause fetal harm.
Advise females of reproductive potential to use effective contraception
during IBRANCE treatment and for at least 3 weeks after the last dose.
IBRANCE may impair fertility in males and has the potential to
cause genotoxicity. Advise male patients with female partners of
reproductive potential to use effective contraception during IBRANCE
treatment and for 3 months after the last dose. Advise females to inform
their healthcare provider of a known or suspected pregnancy. Advise
women not to breastfeed during IBRANCE treatment and for 3 weeks
after the last dose because of the potential for serious adverse
reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade
reported in PALOMA-1 of IBRANCE plus letrozole vs letrozole alone
included neutropenia (75% vs 5%), leukopenia (43% vs 3%), fatigue (41%
vs 23%), anemia (35% vs 7%), upper respiratory infection (31% vs 18%),
nausea (25% vs 13%), stomatitis (25% vs 7%), alopecia (22% vs 3%),
diarrhea (21% vs 10%), thrombocytopenia (17% vs 1%), decreased appetite
(16% vs 7%), vomiting (15% vs 4%), asthenia (13% vs 4%), peripheral
neuropathy (13% vs 5%), and epistaxis (11% vs 1%).

Grade 3/4 adverse reactions (≥10%) in PALOMA-1 reported at
a higher incidence in the IBRANCE plus letrozole group vs the letrozole
alone group included neutropenia (54% vs 1%) and leukopenia (19% vs 0%).
The most frequently reported serious adverse events in patients
receiving IBRANCE plus letrozole were pulmonary embolism (4%) and
diarrhea (2%).

Lab abnormalities occurring in PALOMA-1 (all grades,
IBRANCE plus letrozole vs letrozole alone) were decreased WBC (95% vs
26%), decreased neutrophils (94% vs 17%), decreased lymphocytes (81% vs
35%), decreased hemoglobin (83% vs 40%), and decreased platelets (61% vs
16%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3
of IBRANCE plus fulvestrant vs fulvestrant 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%).

Grade 3/4 adverse reactions (≥10%) in PALOMA-3 reported at
a higher incidence in the IBRANCE plus fulvestrant group vs the
fulvestrant plus placebo group included neutropenia (66% vs 1%) and
leukopenia (31% vs 2%). The most frequently reported serious adverse
reactions in patients receiving IBRANCE plus fulvestrant were infections
(3%), pyrexia (1%), neutropenia (1%), and pulmonary embolism (1%).

Lab abnormalities occurring in PALOMA-3 (all grades,
IBRANCE plus fulvestrant vs fulvestrant plus placebo) were decreased WBC
(99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%),
and decreased platelets (62% vs 10%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must
be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75
mg/day. If the strong inhibitor is discontinued, increase the IBRANCE
dose (after 3-5 half-lives of the inhibitor) to the dose used prior to
the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit
juice may increase plasma concentrations of IBRANCE and should be
avoided. Avoid concomitant use of strong CYP3A inducers. The dose
of sensitive CYP3A substrates with a narrow therapeutic index may
need to be reduced as IBRANCE may increase their exposure.

IBRANCE has not been studied in patients with moderate to
severe hepatic impairment or in patients with severe renal
impairment (CrCl <30 mL/min).

About Pfizer Oncology

Pfizer Oncology is committed to pursuing innovative treatments that have
a meaningful impact on those living with cancer. As a leader in oncology
speeding cures and accessible breakthrough medicines to patients, Pfizer
Oncology is helping to redefine life with cancer. Our strong pipeline of
biologics, small molecules and immunotherapies, one of the most robust
in the industry, is studied with precise focus on identifying and
translating the best scientific breakthroughs into clinical application
for patients across a wide range of cancers. By working collaboratively
with academic institutions, individual researchers, cooperative research
groups, governments and licensing partners, Pfizer Oncology strives to
cure or control cancer with its breakthrough medicines. Because Pfizer
Oncology knows that success in oncology is not measured solely by the
medicines you manufacture, but rather by the meaningful partnerships you
make to have a more positive impact on people’s lives.

Working together for a healthier world®

At Pfizer, we apply science and our global resources to bring therapies
to people that extend and significantly improve their lives. We strive
to set the standard for quality, safety and value in the discovery,
development and manufacture of health care products. Our global
portfolio includes medicines and vaccines as well as many of the world’s
best-known consumer health care products. Every day, Pfizer colleagues
work across developed and emerging markets to advance wellness,
prevention, treatments and cures that challenge the most feared diseases
of our time. Consistent with our responsibility as one of the world’s
premier innovative biopharmaceutical companies, we collaborate with
health care providers, governments and local communities to support and
expand access to reliable, affordable health care around the world. For
more than 150 years, we have worked to make a difference for all who
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In addition, to learn more, please visit us on www.pfizer.com
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DISCLOSURE NOTICE: The information contained in this release is as of
November 10, 2016. 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 IBRANCE
(palbociclib) and an approval in the EU for the treatment of women with
HR+/HER2- locally advanced or metastatic breast 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 IBRANCE; the uncertainties inherent in research and
development, including further investigation of the clinical benefit of
IBRANCE, the ability to meet anticipated clinical trial commencement and
completion dates and regulatory submission dates, as well as the
possibility of unfavorable clinical trial results, including unfavorable
new clinical data and additional analyses of existing clinical data;
whether regulatory authorities will be satisfied with the design of and
results from our clinical studies; whether and when the accelerated
approval for IBRANCE will be converted to regular approval in the U.S.;
whether and when drug applications may be filed in any additional
jurisdictions for IBRANCE for potential HR+/HER2- metastatic breast
cancer indications or in any jurisdictions for any other potential
indications for IBRANCE; whether and when any such applications may be
approved by regulatory authorities, which will depend on the assessment
by such regulatory authorities of the benefit-risk profile suggested by
the totality of the efficacy and safety information submitted; decisions
by regulatory authorities regarding labeling and other matters that
could affect the availability or commercial potential of IBRANCE; 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, 2015 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.

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