First-in-class Therapy Now Approved for Use in a Broader Range of
New Indication Supported by Results of Phase 3 PALOMA-3 Trial of
IBRANCE in Combination with Fulvestrant
NEW YORK–(BUSINESS WIRE)–Pfizer Inc. (NYSE:PFE) today announced that the U.S. Food and Drug
Administration (FDA) has approved a new indication expanding the use of
IBRANCE® (palbociclib) 125mg capsules, Pfizer’s metastatic breast cancer
therapy. Now IBRANCE also is approved for the treatment of hormone
receptor-positive (HR+), human epidermal growth factor receptor
2-negative (HER2-) advanced or metastatic breast cancer in combination
with fulvestrant in women with disease progression following endocrine
therapy.1 Pfizer’s supplemental New Drug Application (sNDA)
for IBRANCE was reviewed and approved under the FDA’s Breakthrough
Therapy designation and Priority Review programs based on results from
the Phase 3 PALOMA-3 trial in pre-, peri- and post-menopausal women with
HR+, HER2- metastatic breast cancer whose disease progressed on or after
prior endocrine therapy in the adjuvant or metastatic setting.1
IBRANCE first was approved in February 2015 and also is indicated for
the treatment of HR+, HER2- advanced or metastatic breast cancer in
combination with letrozole as initial endocrine-based therapy in
postmenopausal women.1 The indication in combination with
letrozole is approved under accelerated approval based on
progression-free survival (PFS). Continued approval for this indication
may be contingent upon verification and description of clinical benefit
in a confirmatory trial.1 The confirmatory Phase 3 trial,
PALOMA-2, is fully enrolled.
IBRANCE is the first and only cyclin-dependent kinase 4/6 (CDK 4/6)
inhibitor approved by the FDA.
“Today’s news gives more women with metastatic breast cancer the
opportunity to benefit from this first-in-class medicine,” said Liz
Barrett, global president and general manager, Pfizer Oncology. “Since
IBRANCE was approved just over one year ago, physicians across the U.S.
have embraced it as a standard of care in the first-line setting. The
expanded approval of IBRANCE is supported by a robust body of evidence
and underscores Pfizer’s continued commitment to addressing the needs of
the metastatic breast cancer community. Pfizer is proud to bring forward
innovative therapies like IBRANCE that make a meaningful difference in
The Phase 3 PALOMA-3 trial enrolled 521 women, regardless of menopausal
status, randomized 2:1 to receive IBRANCE plus fulvestrant or placebo
plus fulvestrant. This trial demonstrated that IBRANCE in combination
with fulvestrant, a standard of care hormonal therapy, prolonged PFS
compared with placebo plus fulvestrant in women with HR+, HER2-
metastatic breast cancer whose disease progressed on or after prior
endocrine therapy.1 Women in the IBRANCE plus fulvestrant arm
had a median PFS of 9.5 months (95% CI: 9.2, 11.0), a substantial
improvement compared with 4.6 months (95% CI: 3.5, 5.6) in the group
treated with placebo plus fulvestrant [HR 0.461 (95% CI: 0.360, 0.591),
p <0.0001].1 Confirmed overall response rate in patients
with measurable disease as assessed by the investigator was 24.6% for
the IBRANCE plus fulvestrant arm compared to 10.9% for the placebo plus
fulvestrant arm.1 Duration of response was 9.3 months in the
IBRANCE plus fulvestrant arm compared with 7.6 months in the placebo
plus fulvestrant arm.1
The warnings and precautions of IBRANCE include neutropenia, pulmonary
embolism and embryo-fetal toxicity.1 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%). For more information, please see Important Safety Information
for IBRANCE below.1
“There currently is no cure for metastatic breast cancer, so ongoing
treatment is usually needed to control the spread of the disease,” said
Marisa Weiss, M.D., chief medical officer and founder, Breastcancer.org.
“That’s why the availability of a first-of-its-kind treatment option
like IBRANCE for women dealing with HR+, HER2- metastatic disease
represents a very important advance.”
Both palbociclib (IBRANCE) combination options are recommended by the
National Comprehensive Cancer Network.2 Palbociclib plus
letrozole is recommended (category 2A) as a first-line treatment for
postmenopausal women with HR+, HER2- metastatic breast cancer.2
Palbociclib plus fulvestrant is recommended (category 1) for
postmenopausal women with HR+, HER2- metastatic breast cancer who have
progressed on endocrine therapy or premenopausal women receiving a
luteinizing hormone-releasing hormone (LHRH) agonist.2
Pfizer believes patients should have access to the medications they
need, and is committed to ensuring that patients who are prescribed
IBRANCE have access to the company’s patient assistance programs.
Patients in the U.S. can visit www.PfizerRxPathways.com and
to learn more.
The full prescribing information for IBRANCE can be found at www.pfizer.com.
Important Safety Information
Neutropenia was the most frequently reported adverse reaction in
Study 1 (75%) and Study 2 (83%). In Study 1, Grade 3 (57%) or 4 (5%)
decreased neutrophil counts were reported in patients receiving IBRANCE
plus letrozole. In Study 2, 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 Study 2. 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 Study 1 (5%) and in
patients treated with IBRANCE plus fulvestrant in Study 2 (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 Study 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 Study 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
Lab abnormalities occurring in Study 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
The most common adverse reactions (≥10%) of any grade reported in Study
2 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 Study 2 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 Study 2 (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 IBRANCE® (palbociclib) 125mg capsules
IBRANCE is an oral inhibitor of CDKs 4 and 6,1 which are key
regulators of the cell cycle that trigger cellular progression.3,4
IBRANCE is indicated 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.1 The
indication in combination with letrozole is approved under accelerated
approval based on progression-free survival (PFS). Continued approval
for this indication may be contingent upon verification and description
of clinical benefit in a confirmatory trial.1
About Pfizer Oncology
Pfizer Oncology is committed to the discovery, investigation and
development of innovative treatment options to improve the outlook for
cancer patients worldwide. Our strong pipeline of biologics and small
molecules, 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 breakthrough medicines, to deliver the right drug for each patient
at the right time. For more information, please visit www.Pfizer.com.
Pfizer Inc.: 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 healthcare products. Our global portfolio
includes medicines and vaccines as well as many of the world’s
best-known consumer healthcare 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, Pfizer has worked to make a difference for all who
rely on us. For more information, please visit us at www.pfizer.com.
In addition, to learn more, follow us on Twitter at @Pfizer
and like us on Facebook at Facebook.com/Pfizer.
DISCLOSURE NOTICE: The information contained in this release is as of
February 19, 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), 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 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 the PALOMA-2 Phase 3 trial of IBRANCE
will demonstrate a statistically significant improvement in
progression-free survival and whether the other trials of IBRANCE will
meet their primary endpoints; whether and when drug applications may be
filed with other jurisdictions for potential HR+/HER2- metastatic breast
cancer indications for IBRANCE; whether and when any other applications
for IBRANCE may be approved by other 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, 2014 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.
1IBRANCE® (palbociclib) Prescribing Information.
New York. NY: Pfizer Inc: 2016.
2 National Comprehensive
Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN
Guidelines®): Breast Cancer. Version 1.2016.
RA. pRb and Control of the Cell Cycle Clock. In: Weinberg RA, ed. The
Biology of Cancer. 2nd ed. New York, NY: Garland Science;
4 Sotillo E, Grana X. Escape from Cellular
Quiescence. In: Enders GH, ed. Cell Cycle Deregulation in Cancer. New
York, NY: Humana Press; 2010:3-22.
Sally Beatty, 212-733-6566