Pfizer’s Novel CDK 4/6 Inhibitor Palbociclib plus Letrozole Significantly Prolonged Progression-Free Survival in Patients with

  Pfizer’s Novel CDK 4/6 Inhibitor Palbociclib plus Letrozole Significantly
  Prolonged Progression-Free Survival in Patients with Advanced Breast Cancer

Final Phase 2 PALOMA-1 Data to Be Presented Today for Potential First-in-Class

 Webcast of Conference Call with Securities Analysts to Review Data Scheduled
                            for Today at 1:30 PDT

AACR Annual Meeting 2014

Business Wire

NEW YORK -- April 6, 2014

Pfizer Inc. today announced detailed results from the PALOMA-1 study, a
randomized Phase 2 study of palbociclib (PD-0332991) in combination with
letrozole. PALOMA-1 achieved its primary endpoint by significantly prolonging
progression-free survival (PFS) compared with letrozole alone in
post-menopausal women with estrogen receptor positive (ER+), human epidermal
growth factor receptor 2 negative (HER2-) locally advanced or metastatic
breast cancer. For women treated with the combination of palbociclib plus
letrozole, the median PFS was 20.2 months, a statistically significant
improvement compared to the 10.2 months of PFS in women who received letrozole
alone (HR=0.488 [95% CI: 0.319, 0.748]; p=0.0004). These data will be
presented today by Dr. Richard S. Finn, associate professor of medicine at
University of California, Los Angeles (UCLA) at the American Association of
Cancer Research (AACR) Annual Meeting 2014 in San Diego (Abstract #CT101).

"These data demonstrate the potential of palbociclib to be a major advance in
the treatment of women with this type of advanced breast cancer," said Dr.
Mace Rothenberg, senior vice president of Clinical Development and Medical
Affairs and chief medical officer for Pfizer Oncology. "We are proud to be at
the forefront of research and development with respect to this promising new
class of investigational anticancer agents and have initiated a broad clinical
development program for palbociclib that includes breast and non-breast

Final results for the secondary efficacy endpoints of duration of treatment
and clinical benefit rate demonstrated superiority in the palbociclib plus
letrozole arm compared to the letrozole-only arm. Per the PALOMA-1 trial
protocol, an initial assessment of overall survival (OS), a secondary
endpoint, was also performed. Based on the events at the time of the
assessment, a median OS of 37.5 months was observed in the combination arm
versus 33.3 months for those who received letrozole alone, a difference of 4.2
months (HR = 0.813, 95% CI: 0.492, 1.345). This OS observation at the time of
final PFS analysis was not statistically significant. A follow-up OS analysis
will be conducted following the accrual of additional events.

The combination of palbociclib and letrozole was generally well-tolerated and
the safety profile of the combination was consistent with previously reported
data. The most common adverse events in the palbociclib plus letrozole arm
were neutropenia (a decrease of the neutrophil count), leukopenia (a decrease
in the total white blood cell count), fatigue and anemia. The neutropenia
observed with the combination in this study was non-cumulative and clinically
manageable. No cases of febrile neutropenia were reported in either arm of the
study. Neutropenia is an on-target, anti-proliferative side effect of
palbociclib and signifies inhibition of CDK4 and its effect on bone marrow.

Palbociclib received Breakthrough Therapy designation from 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. Pfizer continues to work
with the FDA and other regulatory authorities to define the appropriate
regulatory path forward for palbociclib.

Pfizer invites investors and the general public to view and listen to a
webcast of a presentation by Pfizer’s Oncology leadership today at 1:30 p.m.
Pacific Daylight Time, in connection with the presentation of the final
results of PALOMA-1. To view and listen to the webcast, visit our website at and click on the “Review of Palbociclib Phase 2  PALOMA-1
Results at AACR Annual Meeting 2014” webcast link in the For Investors section
located on the lower right-hand corner of that page.

About PALOMA-1

PALOMA-1 (also known as Study 1003 and TRIO-18) is a Phase 2 trial designed to
assess PFS in post-menopausal women with ER+, HER2- advanced breast cancer
receiving 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). This trial consisted of two parts. Part 1
enrolled 66 patients with ER+, HER2- advanced breast cancer. Part 2 enrolled
99 additional patients whose tumors were selected for presence of biomarkers:
cyclin D1 amplification and/or p16 loss. Final results from PALOMA-1 showed
that statistically significant improvement in PFS was achieved for the study
arm (palbociclib + letrozole) in both Parts 1 and 2. PFS is comprised of time
from randomization to time of disease progression or death from any cause.

PALOMA-1 is conducted in collaboration with the Jonsson Cancer Center’s
Revlon/UCLA Women’s Cancer Research Program, led by Dr. Dennis Slamon.
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 a first-line
treatment for post-menopausal patients with ER+, HER2- advanced breast cancer.
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 endocrine therapy.

Additional, investigator-led studies of palbociclib in advanced/metastatic
breast cancer and in early breast cancer are open and enrolling patients,
including the PEARL and PENELOPE-B studies. PEARL, sponsored by Grupo Español
de Investigación en Cáncer de Mama (GEICAM, Spanish Breast Cancer Research
Group), with participation from the Central European Cooperative Oncology
Group (CECOG), is a randomized (1:1), multi-center, open-label Phase 3 study
evaluating palbociclib in combination with exemestane versus capecitabine in
post-menopausal women with ER+, HER2- metastatic breast cancer whose disease
was refractory to previous non-steroidal aromatase inhibitors (letrozole or
anastrozole). PENELOPE-B is 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-operative chemotherapy followed by surgery. This international study is
sponsored by the German Breast Group (GBG).

For more information on these and other ongoing clinical trials of palbociclib
in breast cancer and other tumor types, please visit

About Palbociclib

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.^1

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.^2,3 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).^4,5 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.^6,7 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

DISCLOSURE NOTICE: The information contained in this release is as of April 6,
2014. Pfizer assumes no obligation to update forward-looking statements
contained in this release as the result of new information or future events or

This release contains forward-looking information that involves substantial
risks and uncertainties about palbociclib, an investigational therapy,
including with regard to potential indications. 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 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 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, 2013 and in
its subsequent reports on Form 10-Q and Form 8-K.

^1 Study of Letrozole with or without PD 0332991 for the
first-line treatment of hormone-receptor positive advanced breast cancer.
Available here:
Accessed April 6, 2014.
^2 Shapiro GI. Cyclin-dependent kinase pathways as targets for cancer
treatment. J Clin Oncol. 2006;24(11):1770-1783.
^3 Weinberg RA. The Biology of Cancer. New York, NY. Garland Science; 2013.
^4 Hirama T and H. Phillip Koeffler. Role of the Cyclin-Dependent Kinase
Inhibitors in the Development of Cancer. Blood. 1995; 86: 841-854.
^5 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.
^6 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.
^7 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.


Pfizer Inc.
Sally Beatty, 212-733-6566
Ryan Crowe, 212-733-8160
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