Results Presented at the ESMO 2018 Congress (European Society for
Medical Oncology) and Simultaneously Published in The New England
Journal of Medicine
NEW YORK–(BUSINESS WIRE)–Pfizer Inc.(NYSE:PFE) today announced detailed overall survival (OS)
data from the 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 progressed on or after prior endocrine therapy. In the study,
there was a numerical improvement in OS of nearly seven months with
IBRANCE plus fulvestrant compared to placebo plus fulvestrant, although
this difference did not reach the prespecified threshold for statistical
significance (median OS: 34.9 months [95% CI: 28.8, 40.0] versus 28.0
months [95% CI: 23.6, 34.6]; HR=0.81 [95% CI: 0.64, 1.03], 1-sided
p=0.0429). These data will be presented as a late-breaking oral abstract
during the Presidential Symposium at the ESMO 2018 Congress (European
Society for Medical Oncology) in Munich, Germany, and simultaneously
published in The New England Journal of Medicine.
The difference in median OS demonstrated in this analysis (6.9 months)
is consistent with the improvement previously demonstrated for the
primary endpoint of median progression-free survival (mPFS). In the
updated PFS analysis for this study (non-prespecified), the combination
of IBRANCE plus fulvestrant showed a statistically significant and
clinically meaningful 6.6-month mPFS improvement compared to placebo
plus fulvestrant (11.2 vs. 4.6 months; HR=0.50 [95% CI: 0.40-0.62],
p<0.000001).1 Overall survival is a secondary endpoint of
PALOMA-3, and the trial design was not optimized to detect a
statistically significant difference in OS.
“It’s noteworthy that the magnitude of progression-free survival benefit
observed in PALOMA-3 has translated to a similar difference of nearly
seven months in overall survival, which is clinically meaningful. This
is particularly significant given the challenges of demonstrating
overall survival in this disease setting, where post-progression therapy
is often substantially longer than time on study,” said Massimo
Cristofanilli, M.D., associate director for Translational Research at
the Robert H. Lurie Comprehensive Cancer Center of Northwestern
University, as well as senior investigator of the PALOMA-3 trial. “The
overall survival data, coupled with the previously demonstrated
progression-free survival benefit, are encouraging for patients.”
At the time of this analysis, follow-up was 44.8 months and
approximately 60 percent (n=310) of events had occurred in the 521
patients enrolled. Patients on both arms received up to 10 lines (range
1-10) of post-progression treatment.
The trend toward OS favoring the IBRANCE plus fulvestrant arm was
observed across most subgroups, with hazard ratios consistent with the
overall population. In addition, for the overall population, the
difference in OS was associated with prolonged time from randomization
to first use of chemotherapy post-progression, an exploratory endpoint
(HR=0.58 [95% CI: 0.47, 0.73], 1-sided p<0.000001). Median time to
chemotherapy was 17.6 months (95% CI: 15.2, 19.7) for patients who
received IBRANCE plus fulvestrant, twice that observed in patients who
received placebo plus fulvestrant (8.8 months [95% CI: 7.3, 12.7]).
“Delaying the need for chemotherapy is a central goal of treatment for
women with this disease. These new data from PALOMA-3 show that adding
IBRANCE to fulvestrant led to a substantial improvement in this
important area,” 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 difference
in overall survival and prolonged time to chemotherapy demonstrated in
PALOMA-3 further support the role of IBRANCE in combination with
endocrine therapy as a standard of care in HR+, HER2- metastatic breast
“Looking at the data from the PALOMA-3 trial and across the PALOMA
program, IBRANCE has transformed the treatment landscape for this
disease,” said Mace Rothenberg, M.D., chief development officer,
Oncology, Pfizer Global Product Development. “We are proud of the
compelling body of evidence supporting the use of IBRANCE in this
setting, and the difference this medicine continues to make in the lives
The most common adverse reactions in PALOMA-3 included neutropenia,
leukopenia, infections, fatigue and nausea. No new safety signals
observed with longer follow-up were identified as part of this final OS
About IBRANCE® (palbociclib) 125 mg capsules
IBRANCE is an 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 an aromatase
inhibitor as initial endocrine based therapy in postmenopausal women, or
fulvestrant in women with disease progression following endocrine
IBRANCE currently is approved in more than 85 countries and has been
prescribed to more than 160,000 patients globally.
The full prescribing information for IBRANCE can be found at www.pfizer.com.
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
About Pfizer Oncology
At Pfizer Oncology, we are committed to advancing medicines wherever we
believe we can make a meaningful difference on the lives of patients.
Today, Pfizer Oncology has an industry-leading portfolio of 12 approved
cancer medicines across 20 indications, including breast, prostate,
kidney, lung and hematology. We also have one of the deepest oncology
biosimilars pipelines, with two medicines approved globally and several
assets in mid to late-stage development for the treatment of cancer or
as supportive care. Pfizer Oncology is striving to change the trajectory
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
rely on us. We routinely post information that may be important to
investors on our website at www.pfizer.com. In
addition, to learn more, please visit us on www.pfizer.com
and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn,
and like us on Facebook at Facebook.com/Pfizer.
DISCLOSURE NOTICE: The information contained in this release is as of
October 20, 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; 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
1 Turner NC, André F, Cristofanilli M, et al. Treatment
2 IBRANCE® (palbociclib) Prescribing Information. New
3 Weinberg RA. pRb and Control of the Cell Cycle Clock.
4 Sotillo E, Grana X. Escape from Cellular Quiescence.