|[February 03, 2014]
Pfizer Announces Positive Top-Line Results From PALOMA-1 Evaluating Palbociclib Plus Letrozole in Women with Advanced Breast Cancer
NEW YORK --(Business Wire)--
Pfizer Inc. (NYSE:PFE) today announced that the randomized Phase 2 trial
[PALOMA-1] of palbociclib achieved its primary endpoint by demonstrating
a statistically significant and clinically meaningful improvement in
progression-free survival (PFS) for the combination of palbociclib and
letrozole compared with letrozole alone in post-menopausal women with
estrogen receptor positive (ER+), human epidermal growth factor receptor
2 negative (HER2-) locally advanced or newly diagnosed metastatic breast
"We are delighted with the final data, which suggest the potential for
palbociclib to transform the standard of care for post-menopausal women
with ER+ and HER2- advanced breast cancer. This is encouraging
information for these women, who represent approximately 60 percent of
the advanced breast cancer population," said Dr. Mace Rothenberg, senior
vice president of Clinical Development and Medical Affairs and chief
medical officer for Pfizer Oncology. "We will discuss these results with
the FDA and other regulatory authorities to determine next steps, with
the goal of bringing a much-needed new medicine to patients."
Adverse events observed for the palbociclib arm were consistent with the
known adverse event profile for this combination. Detailed efficacy and
safety data from PALOMA-1 will be submitted for presentation at the
American Association for Cancer Research (AACR) Annual Meeting 2014
scheduled for April 5-9th in San Diego.
Palbociclib received Breakthrough Therapy designation by the United
States Food and Drug Administration (FDA) in April 2013, for the initial
treatment of women with advanced or metastatic ER+, HER2- breast cancer.
This designation was based on interim data from the PALOMA-1 trial. A
randomized, global Phase 3 trial (PALOMA-2) in this patient population
is currently enrolling patients.
PALOMA-1 (also known as Study 1003) is a Phase 2 trial designed to
assess the PFS of palbociclib (125 mg once daily for three out of four
weeks in repeated cycles) in combination with letrozole versus letrozole
alone (2.5 mg once daily on a continuous regimen) in post-menopausal
women with ER+, HER2- advanced breast cancer. PFS is comprised of time
from randomization to time of disease progression or death from any
cause. PALOMA-1 was conducted in collaboration with the Jonsson Cancer
Center's Revlon/UCLA Women's Cancer Research Program. PALOMA-1 is a
multi-center trial with 101 global sites participating.
Palbociclib Development Program in ER+, HER2- Breast Cancer
Pfizer has worked closely with investigators and international breast
cancer experts to establish a robust development program for palbociclib
in ER+, HER2- breast cancer across stages and treatment settings.
Pfizer has initiated two Phase 3 studies of palbociclib in
advanced/metastatic breast cancer. PALOMA-2 (also known as Study 1008)
is a randomized (2:1), multi-center, double blind Phase 3 study that
evaluates palbociclib in combination with letrozole versus letrozole
plus placebo as first-line treatment for post-menopausal patients with
ER+, HER2- advanced breast cancer.1 PALOMA-3 (also known as
Study 1023) is a randomized (2:1), multi-center, double blind Phase 3
study that evaluates palbociclib in combination with fulvestrant versus
fulvestrant plus placebo in women with hormone receptor-positive (HR+),
HER2- metastatic breast cancer whose disease has progressed after prior
Additional, investigator-led studies of palbociclib in
advanced/metastatic breast cancer and in early breast cancer are open
and enrolling patients, including PENELOPE-B, a randomized (1:1), double
blind, placebo-controlled Phase 3 study comparing palbociclib plus
standard endocrine therapy to placebo plus standard endocrine therapy in
patients with HR+, HER2-normal (also known as HER2-) early-stage breast
cancer with certain features that suggest an increased risk for
recurrence after completing pre-operaive chemotherapy followed by
surgery.3 This international study is sponsored by the German
Breast Group (GBG).
For more information on these and other ongoing clinical trials of
palbociclib, please visit www.clinicaltrials.gov.
Palbociclib is an investigational oral targeted agent that selectively
inhibits cyclin-dependent kinases (CDKs) 4 and 6 to regain cell cycle
control and block tumor cell proliferation.4
Loss of cell cycle control is a hallmark of cancer and CDK 4/6 are
overactivated in numerous cancers, leading to loss of proliferative
control.5,6 CDK 4/6 are key regulators of the cell cycle that
trigger cellular progression from growth phase (G1) into phases
associated with DNA replication (S).7,8 CDK 4/6, whose
increased activity is frequent in estrogen receptor-positive (ER+)
breast cancer (BC), are key downstream targets of ER signaling in ER+ BC.9,10
Preclinical data suggest that dual inhibition of CDK 4/6 and ER
signaling is synergistic and has been shown to stop growth of ER+ BC
cell lines in the G1 phase.
Palbociclib is not approved for any indication in any markets.
About Pfizer Oncology
Pfizer Oncology is committed to the discovery, investigation and
development of innovative treatment options to improve the outlook for
cancer patients worldwide. Our strong pipeline of biologics and small
molecules, 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 breakthrough medicines, to deliver the right drug for each patient
at the right time. For more information, please visit www.Pfizer.com.
DISCLOSURE NOTICE: The information contained in this release is as of
February 3. 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 that involves
substantial risks and uncertainties about palbociclib, an
investigational therapy, including potential indications and potential
commercialization. Such risks and uncertainties include, among
other things, 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
PALOMA-2 will demonstrate a statistically significant improvement in
progression-free survival; 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 jurisdictions for
any potential indications for palbociclib; whether and when any such
applications may be approved by regulatory authorities, as well as their
decisions regarding labeling and other matters that could affect the
availability or commercial potential of any such indications; and
A further description of risks and uncertainties can be found under
the heading "Risk Factors" in Pfizer's Annual Report on Form 10-K/A for
the fiscal year ended December 31, 2012 and in its subsequent reports on
Form 10-Q and Form 8-K.
# # # # #
1 Clinicaltrials.gov. A Study of PD-0332991 + Letrozole vs.
Letrozole For 1st Line Treatment Of Postmenopausal Women With ER+/HER2-
Advanced Breast Cancer. Available at: http://clinicaltrials.gov/ct2/show/NCT01740427?term=0332991+and+pfizer&rank=2.
Accessed April 22, 2013.
2 Clinicaltrials.gov. Palbociclib Combined With Fulvestrant
In Hormone Receptor+ HER2-Negative Metastatic Breast Cancer After
Endocrine Failure (PALOMA-3). Available at: http://clinicaltrials.gov/show/NCT01942135.
Accessed November 25, 2013
3 Clinicaltrials.gov. A Study of Palbociclib in Addition to
Standard Endocrine Treatment in Hormone Receptor Positive Her2 Normal
Patients With Residual Disease After Neoadjuvant Chemotherapy and
Surgery (PENELOPE-B). Available at: http://clinicaltrials.gov/show/NCT01864746.
Accessed November 26, 2013
4 Clinicaltrials.gov. Study of Letrozole with or without PD
0332991 for the first-line treatment of hormone-receptor positive
advanced breast cancer. Available here: http://www.clinicaltrials.gov/ct2/show/NCT00721409?term=PD+0332991&rank=10.
Accessed March 28, 2013.
5 Shapiro GI. Cyclin-dependent kinase pathways as targets for
cancer treatment. J Clin Oncol. 2006;24(11):1770-1783.
6 Weinberg RA. The Biology of Cancer. New York, NY. Garland
7 Hirama T and H. Phillip Koeffler. Role of the
Cyclin-Dependent Kinase Inhibitors in the Development of Cancer. Blood.
1995; 86: 841-854.
8 Fry D et al. Specific Inhibition of cyclin-dependent kinase
4/6 by PD 0332991 and associated antitumor activity in human tumor
xenografts. Molecular Cancer Therapeutics. 2004; 3: 1427-1437.
9 Finn RS et al. PD 0332991, a selective cyclin D kinase 4/6
inhibitor, preferentially inhibits proliferation of luminal estrogen
receptor-positive human breast cancer cell lines in vitro. Breast
Cancer Res. 2009;11(5):R77.
10 Lamb R, Lehn S, Rogerson L, Clarke RB, Landberg G. Cell
cycle regulators cyclin D1 and CDK4/6 have estrogen receptor-dependent
divergent functions in breast cancer migration and stem cell-like
activity. Cell Cycle. 2013;12(15):2384-2394.
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