Phase 3 Trial Provides Confirmatory Evidence
for IBRANCE in the First-Line Setting and Will Support Global
Regulatory Submissions
Pfizer Inc. (NYSE:PFE) today announced positive top-line results
from the Phase 3 PALOMA-2 trial for IBRANCE® (palbociclib), an
oral, first-in-class inhibitor of cyclin-dependent kinases (CDKs) 4
and 6.1 The study met its primary endpoint by demonstrating an
improvement in progression-free survival (PFS) for the combination
of IBRANCE plus letrozole compared with letrozole plus placebo in
post-menopausal women with estrogen receptor-positive, human
epidermal growth factor receptor 2-negative (ER+, HER2-) advanced
or metastatic breast cancer who had not received previous systemic
treatment for their advanced disease. The PALOMA-2 trial provides
confirmatory evidence for IBRANCE in combination with letrozole in
the first-line setting, which was first studied in the Phase 2
PALOMA-1 trial. These data will support additional planned global
regulatory submissions and a request for conversion of the
accelerated approval for IBRANCE to regular approval in the U.S.
Detailed efficacy and safety results from PALOMA-2 will be
submitted for presentation at the American Society of Clinical
Oncology (ASCO) 2016 Annual Meeting.
“PALOMA-2 represents the third randomized study to demonstrate
the benefit of IBRANCE when added to hormonal therapy in the
management of women with ER+, HER2- advanced breast cancer. IBRANCE
remains the only CDK 4/6 inhibitor with Phase 3 data in this
disease,” said Dr. Mace Rothenberg, MD, chief medical officer,
Pfizer Oncology & senior vice president, Global Product
Development, Oncology. “These results provide confirmatory evidence
for PALOMA-1 and will be used to support regulatory submissions
around the world, including a request for conversion of IBRANCE
from accelerated to full approval in the United States. We look
forward to sharing the detailed results of PALOMA-2 with the
oncology community and advancing our discussions with regulatory
authorities.”
The adverse events observed with IBRANCE in combination with
letrozole in PALOMA-2 were generally consistent with the known
safety profile for IBRANCE across the different patient populations
and lines of therapy in the clinical development program to date.
The warnings and precautions of IBRANCE include neutropenia,
pulmonary embolism and embryo-fetal toxicity.1 For more
information, please see Important Safety Information for IBRANCE
below.1
Since its introduction in February 2015, more than 25,000 women
have been prescribed IBRANCE by more than 6,000 prescribers in the
U.S.
Based on the results of PALOMA-1, IBRANCE first was approved by
the U.S. Food and Drug Administration (FDA) in February 2015 for
the treatment of postmenopausal women with ER+, HER2- advanced
breast cancer in combination with letrozole as initial
endocrine-based therapy for their metastatic disease.1 The
indication in combination with letrozole was approved under
accelerated approval based on PFS. As stated at the time of the
approval, continued approval for this indication may be contingent
upon verification and description of clinical benefit in PALOMA-2,
which the FDA identified as the confirmatory trial.1 Pfizer will
work with the FDA to submit the results of PALOMA-2 to support
conversion of the accelerated approval for IBRANCE to regular
approval in the U.S.
As previously announced in February 2016, IBRANCE also is
approved in the U.S. for the treatment of hormone receptor-positive
(HR+), HER2-advanced or metastatic breast cancer in combination
with fulvestrant in women with disease progression following
endocrine therapy based on results from the Phase 3 PALOMA-3
study.1
IBRANCE also is approved in eight countries outside of the U.S.,
and Pfizer will work with additional global regulatory authorities
to review the PALOMA-2 data. As previously disclosed in August
2015, Pfizer has filed a Marketing Authorization Application (MAA)
with the European Medicines Agency (EMA) for IBRANCE in combination
with endocrine therapy for the treatment of HR+, HER2- advanced or
metastatic breast cancer. The MAA was based on the results from the
PALOMA-1 and PALOMA-3 trials. Pfizer will work with the EMA to
submit the PALOMA-2 results as additional supporting data for the
ongoing review of the MAA.
About the PALOMA Trials
Pfizer has worked closely with investigators and international
breast cancer experts to establish a robust development program for
IBRANCE in HR+, HER2- breast cancer across stages and treatment
settings.
PALOMA-1
- PALOMA-1 is a randomized (1:1),
multi-center, multinational, open label Phase 2 trial designed to
assess PFS in postmenopausal women with ER+, HER2- advanced breast
cancer receiving IBRANCE (125 mg once daily for three out of four
weeks in repeated cycles) in combination with letrozole versus
letrozole alone (2.5 mg once daily on a continuous regimen) as a
first-line treatment. The results from PALOMA-1 were published
online by The Lancet Oncology in December 2014.
PALOMA-2
- PALOMA-2 is a randomized (2:1),
multicenter, multinational, double-blind Phase 3 study designed to
assess PFS in postmenopausal women with ER+, HER2- advanced breast
cancer receiving IBRANCE (125 mg orally once daily for three out of
four weeks in repeated cycles) in combination with letrozole (2.5
mg once daily continuously) versus letrozole plus placebo as a
first-line treatment. PALOMA-2 has more than 200 global sites
participating and 666 patients enrolled.
PALOMA-3
- PALOMA-3 is a randomized (2:1),
multicenter, multinational, double-blind Phase 3 study designed to
assess PFS with IBRANCE (125 mg once daily orally for three out of
four weeks in each cycle) in combination with fulvestrant (500 mg
intramuscularly on days 1 and 15 of cycle 1, and then on day 1 of
each subsequent 28 day cycle) versus fulvestrant plus placebo in
pre/perimenopausal and postmenopausal women with HR+, HER2-
metastatic breast cancer whose disease has progressed during or
after endocrine therapy. Based on the PALOMA-3 results, a
supplemental New Drug Application (sNDA) was reviewed and approved
in February 2016 under the FDA’s Breakthrough Therapy designation
and Priority Review programs to expand the use of IBRANCE to
include use in combination with fulvestrant in women with HR+,
HER2- advanced or metastatic breast cancer with disease progression
following endocrine therapy.1
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 (PALOMA-1) (75%) and Study 2 (PALOMA-3) (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 diarrhea (2%).
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 16%).
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 @Pfizer_News, LinkedIn, YouTube, and like
us on Facebook at Facebook.com/Pfizer.
DISCLOSURE NOTICE: The information contained in this release is
as of April 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 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 the MAA filed by Pfizer with the EMA for IBRANCE
in combination with endocrine therapy for the treatment of HR+,
HER2- advanced or metastatic breast cancer may be approved and
whether and when any such other 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.
1 IBRANCE® (palbociclib) Prescribing Information. New York. NY:
Pfizer Inc: 2016.
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