-
Results show a positive trend in the secondary endpoint of overall
survival, though not reaching statistical significance
-
IBRANCE is approved worldwide in combination with fulvestrant based
on compelling results from the primary endpoint of progression-free
survival
NEW YORK--(BUSINESS WIRE)--
Pfizer today announced overall survival (OS) results from the Phase 3
PALOMA-3 trial, which evaluated IBRANCE® (palbociclib) in
combination with fulvestrant compared to placebo plus fulvestrant in
women with hormone receptor-positive (HR+), human epidermal growth
factor receptor 2-negative (HER2-) metastatic breast cancer whose
disease has progressed after prior endocrine therapy. The results
demonstrated a positive trend in the hazard ratio favoring the IBRANCE
combination, although this trend did not reach statistical significance.
Overall survival is a secondary endpoint of the PALOMA-3 trial and, as
such, the trial design was not optimized to detect a statistically
significant difference in OS.
“While the difference in overall survival narrowly missed the threshold
for statistical significance – a high bar for any trial in this patient
population – it is similar, in absolute terms, to the improvement in
median progression-free survival previously demonstrated in this trial.1
We are encouraged by these results, which build on the compelling
clinical benefit delivered by IBRANCE,” said Mace Rothenberg, M.D.,
chief development officer, Oncology, Pfizer Global Product Development.
“IBRANCE in combination with endocrine therapy has transformed the
treatment landscape for patients with HR+, HER2- metastatic breast
cancer.”
PALOMA-3 met its primary endpoint of progression-free survival (PFS) at
interim analysis and results were published in The New England
Journal of Medicine in June 2015; updated PFS data were later
presented at the 2016 San Antonio Breast Cancer Symposium. The trial
demonstrated a statistically significant and clinically meaningful
improvement in PFS for IBRANCE plus fulvestrant compared to placebo plus
fulvestrant. PFS is a well-established measure of clinical benefit in
metastatic breast cancer trials.2 IBRANCE in combination with
fulvestrant has been approved in more than 80 countries around the world
based on the PFS demonstrated in PALOMA-3.
“The duration of the survival in hormone receptor-positive metastatic
breast cancer patients, and the potential for subsequent therapies to
confound overall survival outcomes, make demonstrating statistically
significant improvement in overall survival extremely difficult,” said
Nicholas Turner, M.D., Ph.D., professor of molecular oncology 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. “The results from this overall
survival analysis support the strong progression-free survival results
from PALOMA-3 and, while not statistically significant, are encouraging
for physicians and patients. We look forward to presenting the detailed
data at an upcoming medical meeting.”
The most common adverse reactions in PALOMA-3 included neutropenia,
leukopenia, infections, fatigue and nausea; no new safety signals were
identified as part of this final OS analysis.
IBRANCE in combination with endocrine therapy is a standard of care for
HR+, HER2- metastatic breast cancer. IBRANCE has been prescribed to more
than 120,000 patients globally to date.
The full prescribing information for IBRANCE can be found at www.pfizer.com.
About IBRANCE
®
(palbociclib) 125 mg capsules
IBRANCE is an oral inhibitor of CDKs 4 and 6,3 which are key
regulators of the cell cycle that trigger cellular progression.4,5
In the U.S., IBRANCE is indicated for the treatment of HR+, HER2-
advanced or metastatic breast cancer in combination with an aromatase
inhibitor as initial endocrine based therapy in postmenopausal women, or
fulvestrant in women with disease progression following endocrine
therapy.
IMPORTANT IBRANCE
®
(palbociclib) SAFETY
INFORMATION FROM THE U.S. PRESCRIBING INFORMATION
Neutropenia was the most frequently reported adverse reaction in
PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%)
decreased neutrophil counts were reported in patients receiving IBRANCE
plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased
neutrophil counts were reported in patients receiving IBRANCE plus
fulvestrant. Febrile neutropenia has been reported in 1.8% of patients
exposed to IBRANCE across PALOMA-2 and PALOMA-3. 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 15 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.
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-2 for IBRANCE plus letrozole vs placebo plus
letrozole were neutropenia (80% vs 6%), infections (60% vs 42%),
leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%),
alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%),
anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%),
thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite
(15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia
(10% vs 5%).
The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2
for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia
(66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia
(5% vs 2%).
Lab abnormalities of any grade occurring in PALOMA-2 for
IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97%
vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%),
decreased platelets (63% vs 14%), increased aspartate aminotransferase
(52% vs 34%), and increased alanine aminotransferase (43% vs 30%).
The most common adverse reactions (≥10%) of any grade reported in PALOMA-3
for IBRANCE plus fulvestrant vs placebo plus fulvestrant were
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%), diarrhea (24% vs 19%), thrombocytopenia (23% vs
0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%),
decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).
The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3
for IBRANCE plus fulvestrant vs placebo plus fulvestrant were
neutropenia (66% vs 1%) and leukopenia (31% vs 2%).
Lab abnormalities of any grade occurring in PALOMA-3 for
IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC
(99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%),
decreased platelets (62% vs 10%), increased aspartate aminotransferase
(43% vs 48%), and increased alanine aminotransferase (36% vs 34%).
Avoid concurrent use of strong CYP3A inhibitors. If patients must
be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75
mg. 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.
For patients with severe hepatic impairment (Child-Pugh class C),
the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of
IBRANCE have not been studied in patients requiring
hemodialysis.
About Pfizer Oncology
Pfizer Oncology is committed to pursuing innovative treatments that have
a meaningful impact on people living with cancer. Our growing pipeline
of biologics, small molecules and immunotherapies is focused on
identifying and translating the best scientific breakthroughs into
clinical application for patients across a diverse array of solid tumors
and hematologic cancers. Today, we have 10 approved oncology medicines
and 14 assets currently in clinical development. By maximizing our
internal scientific resources and collaborating with other companies,
government and academic institutions, as well as patients and non-profit
and professional organizations, we are bringing together the brightest
and most enterprising minds to take on the toughest cancers. Together we
can accelerate breakthrough treatments to patients around the world and
work to redefine life with cancer.
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 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
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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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DISCLOSURE NOTICE: The information contained in this release is as of
June 25, 2018. 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 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; the risk that clinical trial data
are subject to differing interpretations, and, even when we view data as
sufficient to support the safety and/or effectiveness of a product
candidate, regulatory authorities may not share our views and may
require additional data or may deny approval altogether; whether
regulatory authorities will be satisfied with the design of and results
from our clinical studies; 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
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, 2017 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 Turner NC, André F, Cristofanilli M, et al. Treatment
postprogression in women with endocrine-resistant HR+/HER2- advanced
breast cancer who received palbociclib plus fulvestrant in PALOMA-3. In:
Proceedings of the 2016 San Antonio Breast Cancer Symposium; Dec 6-10,
2016; San Antonio, TX. Abstract P4-22-06.
2 Song SY, Seo H, Kim G, Kim AR, Kim EY. Trends in endpoint
selection in clinical trials of advanced breast cancer. Cancer Res
Clin Oncol. 2016;142(11):2403–2413.
3 IBRANCE® (palbociclib) Prescribing Information. New York.
NY: Pfizer Inc: 2018.
4 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.
5 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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Source: Pfizer Inc.