First-in-class IBRANCE in Combination with Letrozole Exceeded 2
Years in Median PFS
NEW YORK–(BUSINESS WIRE)– Pfizer Inc. (NYSE:PFE) today announced that detailed results from the
Phase 3 PALOMA-2 trial were published in The New England
Journal of Medicine. These data, presented at the 52nd
American Society of Clinical Oncology (ASCO) Annual Meeting in June,
further demonstrate the clinical benefit of IBRANCE®
(palbociclib) as initial therapy for postmenopausal women with estrogen
receptor-positive, human epidermal growth factor receptor 2-negative
(ER+, HER2-) metastatic breast cancer. The PALOMA-2 study showed the
combination of IBRANCE and letrozole extended progression-free survival
(PFS), or the amount of time before tumor growth, by more than 10 months
compared with letrozole plus placebo. Further, the study demonstrated
that the median PFS of the IBRANCE and letrozole combination exceeded
two years – making it the first and only treatment for this population
of women to do so in a randomized Phase 3 study.1
“The median PFS of more than two years observed in this study is
unprecedented for this patient population,” said Veronique Dieras, M.D.,
medical oncologist and head of clinical research, Clinical
Investigational Unit Chef de Service Recherche Clinique, Unité
d’Investigation Clinique Department of Medical Oncology, Institut Curie,
Paris, France. “Building on the Phase 2 PALOMA-1 data, the results of
PALOMA-2 provide additional evidence that the combination of IBRANCE and
letrozole is a meaningful advancement for these women.”
“Since its accelerated approval in 2015, IBRANCE in combination with
letrozole has become a standard of care for the treatment of
post-menopausal women with ER+, HER2- advanced or metastatic breast
cancer,” said Hope Rugo, M.D., professor of medicine and director of
breast oncology and clinical trials education at the University of
California San Francisco Helen Diller Family Comprehensive Cancer
Center. “We now have seen consistent results across three randomized
trials in which the addition of IBRANCE to an endocrine therapy
significantly prolonged PFS compared to the endocrine therapy alone.”
In the trial, median PFS for women treated with IBRANCE plus letrozole
was 24.8 months (95% CI, 22.1-not estimable) compared with 14.5 months
(95% CI, 12.9-17.1) for women treated with letrozole plus placebo
(HR=0.58 [95% CI, 0.46-0.72], p<0.001), a 42% reduction in the risk of
disease progression.
“IBRANCE has raised the bar for new treatments in hormone-receptor
positive advanced breast cancer. The results of this Phase 3 trial add
to the growing body of clinical data in support of IBRANCE and
translates into hope for patients,” said Mace Rothenberg, M.D., chief
development officer, Oncology, Pfizer Global Product Development. “We
look forward to sharing the full PALOMA-2 data with global regulatory
authorities with the goal of making IBRANCE available to more women
around the world. Pfizer is proud of being a leader in the development
of innovative therapies like IBRANCE that make a meaningful difference
in patients’ lives.”
Safety results were consistent with PALOMA-1 and no major unexpected
safety findings were observed. The most common grade 3/4 adverse events
with IBRANCE plus letrozole versus placebo plus letrozole were
neutropenia (66.4% vs 1.4%), leukopenia (24.8% vs 0%), infections (6.5%
vs 3.2%) and anemia (5.4% vs 1.8%). Febrile neutropenia was reported in
1.8% of patients in the IBRANCE plus letrozole group and none of the
patients in the placebo plus letrozole group. For more information,
please see Important Safety Information for IBRANCE below.2
IBRANCE first was approved by the U.S. Food and Drug Administration
(FDA) in February 2015 and is indicated for the treatment of hormone
receptor positive (HR+), HER2- advanced or metastatic breast cancer in
combination with letrozole as initial endocrine-based therapy in
postmenopausal women.2 The indication in combination with
letrozole was approved under accelerated approval based on PFS results
from the Phase 2 PALOMA-1 study. As stated at the time of the approval,
continued approval for this indication may be contingent upon
verification and description of clinical benefit in a confirmatory
trial, the double-blind, Phase 3 PALOMA-2 study.2 A
supplemental New Drug Application to support the conversion of the
accelerated approval to regular approval based on the results of
PALOMA-2 has been submitted to the FDA.
IBRANCE also is approved in the U.S. for the treatment of 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.2
Since the initial approval in February 2015, more than 40,000 women have
been prescribed IBRANCE by more than 8,500 prescribers in the U.S.
As previously disclosed, the European Commission has approved IBRANCE
for the treatment of women with 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. In total, IBRANCE is approved in more
than 50 countries.
About PALOMA-2
PALOMA-2 is a randomized (2:1), multicenter, multinational, double-blind
Phase 3 study designed to assess the PFS of 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 for postmenopausal women with ER+,
HER2- metastatic breast cancer. PALOMA-2 evaluated a total of 666 women
from 186 global sites in 17 countries.
The full prescribing information for IBRANCE can be found at www.pfizer.com.
About IBRANCE® (palbociclib) 125 mg capsules
IBRANCE is the first and only FDA approved oral inhibitor of CDKs 4 and
6,2 which are key regulators of the cell cycle that trigger
cellular progression.3,4 In the U.S., 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.2 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, PALOMA-2.2
Important IBRANCE (palbociclib) Safety Information from the U.S.
Prescribing Information
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.
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
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In addition, to learn more, follow us on Twitter at @Pfizer
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DISCLOSURE NOTICE: The information contained in this release is as of
November 16, 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 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 Based on a MEDLINE® literature review for Phase 3 trials in
HR+/HER2- MBC treatment as of August 2016.
2 IBRANCE®
(palbociclib) Prescribing Information. New York. NY: Pfizer Inc: 2016.
3
Weinberg RA. pRb and Control of the Cell Cycle Clock. In: Weinberg RA,
ed. The Biology of Cancer. 2nd ed. New York, NY: Garland Science;
2014:275-329.
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.
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Contacts
Pfizer Inc.
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or
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Source: Pfizer Inc.
Cet article PALOMA-2 Phase 3 Study Published In The New England Journal Of
Medicine Demonstrates Clinical Benefit Of Pfizer’s IBRANCE®
(palbociclib) In First-Line ER+, HER2- Metastatic Breast Cancer est apparu en premier sur EEI-BIOTECHFINANCES.