Results Presented at the ESMO 2018 Congress
(European Society for Medical Oncology) and Simultaneously
Published in The New England Journal of Medicine
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 cancer.”
“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 of patients.”
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 analysis.
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 therapy.
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 hemodialysis.
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 of cancer.
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
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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 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 IBRANCE® (palbociclib) Prescribing
Information. New York. NY: Pfizer Inc: 2018.
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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version on businesswire.com: https://www.businesswire.com/news/home/20181020005011/en/
Pfizer U.S. Media Contact:Jessica Smith,
212-733-6213Jessica.M.Smith@pfizer.comorPfizer Investor
Contact:Ryan Crowe, 212-733-8160Ryan.Crowe@pfizer.com
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