Pfizer Inc. (NYSE:PFE) today announced overall survival (OS)
results from the Phase 3 PALOMA-2 trial, which evaluated IBRANCE®
(palbociclib) in combination with letrozole compared to placebo
plus letrozole for the first-line treatment of postmenopausal women
with estrogen receptor-positive (ER+), human epidermal growth
factor receptor 2-negative (HER2-) metastatic breast cancer (mBC).
With a median follow-up of 90 months, patients receiving IBRANCE in
combination with letrozole had numerically longer OS compared to
placebo plus letrozole (median (95% CI) 53.9 months (49.8–60.8) vs
median 51.2 months (43.7–58.9)); the results were not statistically
significant (Hazard Ratio (HR)=0.956 [95% CI, 0.777–1.177]). The
PALOMA-2 trial was designed for a primary endpoint of
progression-free survival (PFS) with OS as one of the secondary
endpoints. The results will be presented today as an oral
presentation at the American Society of Clinical Oncology (ASCO)
2022 Annual Meeting (LBA 1003).
“IBRANCE continues to provide substantial benefit as a
first-line treatment for adults with HR+, HER2- mBC based on strong
progression-free survival data, which formed the basis of its
worldwide approvals,” said Chris Boshoff, M.D., Ph.D., Chief
Development Officer, Oncology, Pfizer Global Product Development.
“Interpretation of OS in PALOMA-2 is limited by the large and
disproportionate censoring of patients with missing survival data
between treatment arms. We remain confident in the compelling
benefits that IBRANCE plus endocrine therapy offers to this patient
population, which is underscored by data from PALOMA-2 showing
delayed time to chemotherapy, maintenance of quality of life and a
consistent safety profile. Pfizer continues to invest in expanding
the treatment options for people living with metastatic breast
cancer.”
“IBRANCE transformed the treatment landscape for patients with
HR+, HER2- MBC when it was approved in 2015, representing the first
new treatment in this patient population in over a decade,” said
Richard Finn, M.D., Professor of Medicine at the UCLA David Geffen
School of Medicine and Jonsson Comprehensive Cancer Center.
“PALOMA-2 enrolled a diverse patient population including patients
whose disease was first diagnosed in the metastatic stage as well
as those with Disease Free Interval (DFI) less than 12 months from
adjuvant treatment and those with greater than 12 months following
adjuvant treatment. The median survival of over 50 months in this
population represents a significant improvement in the natural
history of HR+ breast cancer.”
PALOMA-2 met its primary endpoint of PFS in 2016 and was
published in The New England Journal of Medicine in November 2016.
The results demonstrated IBRANCE plus letrozole resulted in an
improved median PFS of 24.8 months when compared to 14.5 months
with placebo plus letrozole (HR=0.580). The PALOMA-2 trial showed
that in addition to substantially delaying progressive disease,
IBRANCE as first-line treatment, in combination with letrozole,
delayed time to chemotherapy (38.1 months vs 29.8 months; HR,
0.73), while maintaining quality of life with no new identified
safety issues.
The OS analysis being presented at ASCO included a large
proportion of patients with missing survival data (i.e. patients
who withdrew consent or were lost to follow-up) and were censored
(assumed to be alive) at the time of the analysis: 13% in the
treatment arm versus 21% in the control arm. Also of note, 10% of
IBRANCE plus letrozole and 2% of placebo plus letrozole patients
were still on study treatment at the time of the final analysis.
The most common adverse reactions in PALOMA-2 included neutropenia,
leukopenia, infections, fatigue and nausea.
IBRANCE continues to be a leader in the CDK4/6 inhibitor class,
prescribed to over 450,000 patients across more than 100 countries,
and seven out of 10 patients in the U.S. who are prescribed a
CDK4/6 inhibitor receiving an IBRANCE prescription.i
About the PALOMA-2 Study
PALOMA-2 is a randomized (2:1), multicenter, multinational,
double-blind Phase 3 study designed to assess the efficacy (defined
by PFS) and safety 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. Patients were to be
stratified by site of disease (visceral, non-visceral), by
disease-free interval since completion of prior (neo)adjuvant
therapy (de novo metastatic, ≤12 months, >12 months), and by the
nature of prior (neo)adjuvant anti-cancer treatment received (prior
hormonal therapy, no prior hormonal therapy). The primary endpoint
was progression-free survival, as assessed by the investigators;
secondary endpoints were overall survival, objective response,
clinical benefit response, patient-reported outcomes,
pharmacokinetic effects, and safety.
About the IBRANCE Real-World Evidence Program
The IBRANCE Real-World Evidence (RWE) program is generating data
from multiple studies involving more than 8,000 patients around the
world. These studies include diverse patient populations treated in
everyday clinical practice and are collecting data related to
clinical outcomes, translational data and quality of life
endpoints, which complement the data generated from the PALOMA
randomized clinical trials. Most recently, Pfizer reported results
from a retrospective comparative effectiveness study of 2,888 men
and postmenopausal women with HR+, HER2- mBC evaluating IBRANCE in
the real-world, first-line setting in combination with aromatase
inhibitors (AI) compared to AI alone. Pfizer will continue to share
new data from these studies with the scientific community as
results become available.
About IBRANCE® (palbociclib) 125 mg tablets and
capsules
IBRANCE is an oral inhibitor of CDKs 4 and 6,ii which are key
regulators of the cell cycle that trigger cellular
progression.iii,iv In the U.S., IBRANCE is indicated for the
treatment of adult patients with HR+, HER2- advanced or metastatic
breast cancer in combination with an aromatase inhibitor as initial
endocrine-based therapy in postmenopausal women or in men; or with
fulvestrant in patients with disease progression following
endocrine therapy.
The full U.S. Prescribing Information for the IBRANCE tablets
and the IBRANCE capsules can be found here and here.
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.
Severe, life-threatening, or fatal interstitial lung disease
(ILD) and/or pneumonitis can occur in patients treated with
CDK4/6 inhibitors, including IBRANCE when taken in combination with
endocrine therapy. Across clinical trials (PALOMA-1, PALOMA-2,
PALOMA-3), 1.0% of IBRANCE-treated patients had ILD/pneumonitis of
any grade, 0.1% had Grade 3 or 4, and no fatal cases were reported.
Additional cases of ILD/pneumonitis have been observed in the
post-marketing setting, with fatalities reported.
Monitor patients for pulmonary symptoms indicative of
ILD/pneumonitis (e.g. hypoxia, cough, dyspnea). In patients who
have new or worsening respiratory symptoms and are suspected to
have developed pneumonitis, interrupt IBRANCE immediately and
evaluate the patient. Permanently discontinue IBRANCE in patients
with severe ILD or pneumonitis.
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
to consider sperm preservation before taking IBRANCE. 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 in the
lives of people living with cancer. Today, we have an
industry-leading portfolio of 24 approved innovative cancer
medicines and biosimilars across more than 30 indications,
including breast, genitourinary, colorectal, blood and lung
cancers, as well as melanoma.
About Pfizer: Breakthroughs That Change Patients’
Lives
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, including innovative medicines and vaccines. 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 170 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, YouTube and like us
on Facebook at Facebook.com/Pfizer.
DISCLOSURE NOTICE: The information contained in this
release is as of June 4, 2022. 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;
uncertainties regarding the commercial impact of the overall
survival results of the PALOMA-2 trial; the uncertainties inherent
in research and development, including the ability to meet
anticipated clinical endpoints, commencement and/or completion
dates for our clinical trials, regulatory submission dates,
regulatory approval dates and/or launch dates, as well as the
possibility of unfavorable new clinical data and further analyses
of existing clinical data; the risk that clinical trial data are
subject to differing interpretations and assessments by regulatory
authorities; whether regulatory authorities will be satisfied with
the design of and results from our clinical studies; whether and
when biologic license applications may be filed in any
jurisdictions for IBRANCE for any additional indications for
IBRANCE; whether and when any such applications may be approved by
regulatory authorities, which will depend on myriad factors,
including making a determination as to whether the product's
benefits outweigh its known risks and determination of the
product's efficacy and, if approved, whether IBRANCE will be
commercially successful; decisions by regulatory authorities
impacting labeling, manufacturing processes, safety and/or other
matters that could affect the availability or commercial potential
of IBRANCE; uncertainties regarding the ability to obtain
recommendations from advisory or technical committees and other
public health authorities regarding IBRANCE and uncertainties
regarding the commercial impact of any such recommendations; the
impact of COVID-19 on our business, operations and financial
results; 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, 2021 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.
____________________________ i Pfizer Data on File – IQVIA
February 2021. ii IBRANCE® (palbociclib) Prescribing Information.
New York. NY: Pfizer Inc: 2019. iii 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. iv
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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