Partnership with Pfizer, BIG, GBG, NSABP and PrECOG to facilitate
further investigation of IBRANCE
The Alliance Foundation Trials, LLC (AFT), the Austrian Breast
& Colorectal Cancer Study Group (ABCSG) and Pfizer Inc.
today announced the launch of the Palbociclib Collaborative
Adjuvant Study, or PALLAS. This global Phase 3
clinical trial for patients with early-stage breast cancer is being
conducted in conjunction with Breast International Group (BIG), German
Breast Group (GBG), National Surgical Adjuvant Breast and Bowel Project
(NSABP) and PrECOG, LLC (PrECOG). The PALLAS trial will evaluate whether
the addition of IBRANCE® (palbociclib), developed by Pfizer,
to standard therapy will improve disease-free survival and prevent the
disease from recurring. Patients treated in this study will have cancers
that are hormone receptor-positive (HR+), meaning their growth is fueled
by the hormone estrogen, but are negative for human epidermal growth
factor receptor 2 (HER2-), a different tumor-associated protein. About
60 to 65 percent of breast cancers in the United States fall into this
category.i
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“We are delighted that Alliance was chosen to co-lead the PALLAS trial
along with our partners at ABCSG,” said Monica M. Bertagnolli, MD,
president and chief executive officer of AFT, and group chair and
principal investigator of the Alliance for Clinical Trials in Oncology.
“This exciting study examines a new CDK 4/6 inhibitor that has already
demonstrated an impact for breast cancer patients with metastatic
disease. The goal is to determine whether IBRANCE can also improve the
disease-free survival rate in patients with surgically resectable
disease.”
“After intensively working together among trial leadership on the
scientific conception, operational preparation and seamless
transatlantic cooperation for this clinical trial, we are excited that
this study, with the potential to revolutionize adjuvant therapy for the
most common type of breast cancer, is now ready to start,” said
Professor Michael Gnant, MD, FACS, president of the ABCSG, and head of
the Breast Health Center Vienna. “We are convinced that this global
venture has potential to bring great benefit to our breast cancer
patients."
A hallmark of cancer cell growth is loss of control of the cell cycle,
leading to unregulated growth and spread of cancer. A promising strategy
to overcome this process involves inhibition of enzymes called
cyclin-dependent kinases (CDKs), which allows re-establishment of
control of cell growth. iii,iv Recent research has shown that
two related enzymes – CDK 4 and CDK 6 – are among the primary proteins
that accelerate cancer cell growth, and may be particularly important in
HR+ breast tumors. iii,iv Research also indicates that
combining CDK 4/6 inhibitors with endocrine therapy is beneficial in
patients with advanced breast cancer.iii,iv The new oral,
anti-cancer drug IBRANCE blocks CDK 4/6.ii
IBRANCE was approved in February 2015 by the U.S. Food and Drug
Administration (FDA) for the treatment of postmenopausal women with
estrogen receptor-positive (ER+)/HER2- advanced breast cancer as initial
endocrine-based therapy for their metastatic disease. This indication is
approved under accelerated approval based on progression-free survival,
the length of time during or after treatment a patient lives with a
disease but does not get worse.ii Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in a confirmatory trial. The confirmatory Phase 3
trial, PALOMA-2, is fully enrolled.
“We have seen exciting news about IBRANCE in 2015, not only from the
accelerated approval based on PALOMA-1, but also from the results of the
PALOMA-3 study, a Phase 3 trial showing the addition of IBRANCE to the
hormone medicine fulvestrant in pre-treated patients with metastatic
HR+/HER2- breast cancer improved clinical outcomes,” said Erica L.
Mayer, MD, MPH, co-principal investigator of the trial for AFT,
Assistant Professor of Medicine at the Harvard Medical School and Senior
Physician at the Susan F. Smith Center for Women's Cancers and at the
Dana-Farber Cancer Institute.
“The primary endpoint of the PALLAS trial is to look at the time to
disease recurrence in patients who have stage 2 or stage 3 breast
cancer,” Dr. Mayer said. “The study is also enriched with an expansive
correlative science program that includes analyses of patient tissue and
blood samples, as well as an in depth analysis of patient adherence to
oral medication and patients’ quality of life while on study.”
The PALLAS trial is a prospective, two-arm, international, multicenter,
randomized, open-label Phase 3 study. The trial is open to premenopausal
and postmenopausal women or men with stage 2 or stage 3 HR+/HER2- early
breast cancer. Participants will be randomized (selected by chance) to
one of two treatment arms. One study arm will treat patients with
IBRANCE (at a dose of 125 mg orally once daily, day 1 to day 21 followed
by seven days off treatment in a 28-day cycle) for two years and
standard endocrine adjuvant therapy for at least five years. The other
study arm will treat patients with standard endocrine adjuvant therapy
alone for at least five years. Participants will be recruited worldwide.
Approximately 4,600 people are expected to enroll in the trial.
“We’re looking for ways that we can prevent recurrence of breast cancer
in every patient. IBRANCE appears to be very promising in that regard
because it boosted the effect of anti-estrogen treatments in women who
already have recurrent, metastatic breast cancer,” said Angela
DeMichele, MD, MSCE, co-principal investigator for PrECOG, Miller
Associate Professor of Breast Cancer Excellence in the Rowan Breast
Center and Associate Professor of Medicine and Epidemiology at the
Abramson Cancer Center of the University of Pennsylvania.
The scope of the PALLAS trial is global. AFT and the ABCSG have brought
together a collaborative group of breast cancer specialists from around
the world to team up with Pfizer to form a unique public-private cancer
research partnership aimed at bringing more innovative therapies to
patients in more efficient ways.
“Collaborations of this kind are crucial to advance the science and
general understanding of how we can best treat breast cancer,” said
Maria Koehler, MD, PhD, vice president of Strategy, Innovation and
Collaborations for Pfizer Oncology. “Working together, we will be able
to efficiently answer important clinical questions in order to
potentially bring IBRANCE to patients with early-stage breast cancer who
need the treatment most.”
“Pfizer is honored to partner with prominent breast cancer research
groups to explore the use of IBRANCE for women and men with
HR+/HER2- early-stage breast cancer, which affects millions of patients
each year globally. This collaboration allows Pfizer to tap into many of
the most respected scientific minds and well-established large global
research networks to conduct a large, international Phase 3 trial,” said
Dr. Mace Rothenberg, senior vice president of Clinical Development and
Medical Affairs and chief medical officer for Pfizer Oncology.
Availability
Currently, the new study is open to physicians and medical facilities
throughout the U.S. if they are associated with Alliance, NSABP or
PrECOG. The study will be available to non-U.S. sites beginning in
October through an extended academic core network, including the ABCSG
and BIG.
Funding and Sponsorship
Pfizer, the manufacturer of IBRANCE, is providing AFT and ABCSG with
funding support for this trial. AFT is sponsoring the trial in the U.S.
and ABCSG for all non-U.S. sites.
For questions about this trial, please contact PALLAS_AFT@alliancefoundationtrials.org.
Global Partners
About Alliance Foundation Trials, LLC
Alliance Foundation Trials, LLC (AFT) is a research organization that
develops and conducts cancer clinical trials, working closely with
pharmaceutical partners, research collaborators and the Alliance for
Clinical Trials in Oncology member network. AFT seeks to fulfill the
vision of the Alliance for Clinical Trials in Oncology to reduce the
impact of cancer on people by uniting a broad community of scientists
and clinicians from many disciplines, committed to discovering,
validating and disseminating effective strategies for the prevention and
treatment of cancer. AFT is funded wholly by private entities and does
not use any public funding resources.
About ABCSG
The Austrian Breast & Colorectal Cancer Study Group (ABCSG) is Austria’s
biggest and best-established academic research organization that
internationally successfully performs clinical trials focusing on the
subject of breast and colorectal cancer, and more recently also on
pancreatic cancer and liver metastasis. ABCSG has over time and
dedication achieved a very high public reputation and patient
commitment. In some indications, more than 35 percent of all breast
cancer patients with a given diagnosis are recruited into ABCSG trials.
Since 1984, more than 25,000 patients have participated in ABCSG
studies, and over 900 physicians are part of the extensive ABCSG’s
network. For further information, visit www.abcsg.com
About BIG
The Breast International Group (BIG) is an international non-profit
organization for academic breast cancer research groups from around the
world. BIG facilitates and accelerates breast cancer research at the
international level by stimulating cooperation between its 56 member
groups and other academic networks, and collaborating with, but working
independently from, the pharmaceutical industry. Linked to more than
3,000 hospitals, BIG is the largest international network dedicated
solely to breast cancer. Working together towards one goal: to cure
breast cancer! For more information, visit www.bigagainstbreastcancer.org.
About NSABP Foundation, Inc.
The NSABP Foundation is a not-for-profit academic research organization,
which continues to build upon its nearly 60-year history of conducting
with its member institutions ground-breaking research studies and
educational activities in breast and colorectal cancers, which are
designed to improve the outcome for cancer patients via improved
therapeutic and prevention modalities. Over the last fifteen years, the
Foundation has established full service capabilities to conduct
independently-funded international research with the private sector to
evaluate promising new agents. More recently, the Foundation continues
to maintain a close working relationship with NCI initiatives as a
founding member of NRG Oncology. Also, it has expanded its service
offerings to the private sector across a wide range of capabilities from
pre-clinical research through Phase 3 clinical trials focused on
biomarker driven studies. For more information visit www.nsabp.org.
About PrECOG
PrECOG is a not-for-profit limited liability company formed in 2006 by
the ECOG Research and Education Foundation, Inc. Through this
relationship, key opinion leaders and the entire network of ECOG
investigators and institutions underpin PrECOG. Funded entirely outside
of the public health system, PrECOG uses an operational structure
separate from ECOG for all facets of clinical trial management. PrECOG
typically functions as the sponsor and holds the IND, or works under
company owned INDs with transfer of obligations. For more information,
visit www.precogllc.org.
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, visit www.Pfizer.com.
About IBRANCE®
IBRANCE (palbociclib) is an oral inhibitor of CDKs 4 and 6.ii
CDKs 4 and 6 are key regulators of the cell cycle that trigger cellular
progression.iii,iv IBRANCE is indicated in the U.S. for use
in combination with letrozole for the treatment of postmenopausal women
with estrogen receptor-positive, human epidermal growth factor receptor
2-negative (ER+/HER2-) advanced breast cancer as initial endocrine-based
therapy for their metastatic disease.ii IBRANCE is not
approved for the use being investigated in the PALLAS trial.
The effectiveness of IBRANCE in these patients is based on a study that
measured progression-free survival.ii Continued approval for
this indication may be contingent upon verification and description of
clinical benefit in a confirmatory trial.
IMPORTANT IBRANCE (palbociclib) SAFETY INFORMATION
Neutropenia: Neutropenia is frequently reported with IBRANCE
therapy. In the randomized phase II study, Grade 3 (57%) or 4 (5%)
decreased neutrophil counts were reported in patients receiving IBRANCE
plus letrozole. Febrile neutropenia can occur.
Monitor complete blood count prior to starting IBRANCE and at the
beginning of each cycle, as well as Day 14 of the first two cycles, and
as clinically indicated. For patients who experience Grade 3
neutropenia, consider repeating the complete blood count monitoring 1
week later. Dose interruption, dose reduction, or delay in starting
treatment cycles is recommended for patients who develop Grade 3 or 4
neutropenia.
Infections: Infections have been reported at a higher rate in
patients treated with IBRANCE plus letrozole (55%) compared with
letrozole alone (34%). Grade 3 or 4 infections occurred in 5% of
patients treated with IBRANCE plus letrozole vs no patients treated with
letrozole alone. Monitor patients for signs and symptoms of infection
and treat as medically appropriate.
Pulmonary embolism (PE): PE has been reported at a higher
rate in patients treated with IBRANCE plus letrozole (5%) compared with
no cases in patients treated with letrozole alone. Monitor patients for
signs and symptoms of PE and treat as medically appropriate.
Pregnancy and lactation: Based on the mechanism of action,
IBRANCE can cause fetal harm. Advise females with reproductive potential
to use effective contraception during therapy with IBRANCE and for at
least 2 weeks after the last dose. Advise females to contact their
healthcare provider if they become pregnant or if pregnancy is suspected
during treatment with IBRANCE. Advise women not to breastfeed while on
IBRANCE therapy because of the potential for serious adverse reactions
in nursing infants from IBRANCE.
Additional hematologic abnormalities: Decreases in hemoglobin
(83% vs 40%), leukocytes (95% vs 26%), lymphocytes (81% vs 35%), and
platelets (61% vs 16%) occurred at a higher rate in patients treated
with IBRANCE plus letrozole vs letrozole alone.
Adverse reactions: The most common all causality adverse
reactions (≥10%) of any grade reported in patients treated with IBRANCE
plus letrozole vs letrozole alone in the phase II study included
neutropenia (75% vs 5%), leukopenia (43% vs 3%), fatigue (41% vs 23%),
anemia (35% vs 7%), upper respiratory infection (31% vs 18%), nausea
(25% vs 13%), stomatitis (25% vs 7%), alopecia (22% vs 3%), diarrhea
(21% vs 10%), thrombocytopenia (17% vs 1%), decreased appetite (16% vs
7%), vomiting (15% vs 4%), asthenia (13% vs 4%), peripheral neuropathy
(13% vs 5%), and epistaxis (11% vs 1%).
Grade 3/4 adverse reactions reported (≥10%) occurring at a higher
incidence in the IBRANCE plus letrozole vs letrozole alone group include
neutropenia (54% vs 1%) and leukopenia (19% vs 0%). The most frequently
reported serious adverse events in patients receiving IBRANCE were
pulmonary embolism (4%) and diarrhea (2%).
General dosing information: The recommended dose of IBRANCE is
125 mg taken orally once daily for 21 days followed by 7 days off
treatment in 28-day cycles. IBRANCE should be taken with food and in
combination with letrozole 2.5 mg once daily continuously.
Patients should be encouraged to take their dose at approximately the
same time each day.
Capsules should be swallowed whole. No capsule should be ingested if it
is broken, cracked, or otherwise not intact. If a patient vomits or
misses a dose, an additional dose should not be taken that day. The next
prescribed dose should be taken at the usual time.
Management of some adverse reactions may require temporary dose
interruption/delay and/or dose reduction, or permanent discontinuation.
Dose modification of IBRANCE is recommended based on individual safety
and tolerability.
Drug interactions: Avoid concurrent use of strong CYP3A
inhibitors. If patients must be administered a strong CYP3A inhibitor,
reduce the IBRANCE dose to 75 mg/day. 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 and moderate CYP3A inducers. The dose of
the sensitive CYP3A substrates with a narrow therapeutic index may need
to be reduced as IBRANCE may increase their exposure.
Hepatic and renal impairment: IBRANCE has not been studied in
patients with moderate to severe hepatic impairment or in patients with
severe renal impairment (CrCl <30 mL/min).
PFIZER DISCLOSURE NOTICE: The information contained in this
release is as of August 26, 2015. 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 a potential additional indication for the
treatment of HR+/HER2- early breast cancer and 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 further
investigation of the clinical benefit of IBRANCE, 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 the PALOMA-2
Phase 3 trial of IBRANCE will demonstrate a statistically significant
improvement in progression-free survival and whether the other trials of
IBRANCE will meet their primary endpoints; whether regulatory
authorities will be satisfied with the design of and results from our
clinical studies; whether and when drug applications or supplemental
drug applications may be filed with the U.S. Food and Drug
Administration or any other jurisdictions for initial or additional
indications for IBRANCE, including the potential additional indication;
whether and when any such 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, 2014 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 SEC
and available at www.sec.gov
and www.pfizer.com.
i Decision Resources. Event Driven Pharmacor Report. 2012.
ii IBRANCE® (palbociclib) Prescribing Information.
New York. NY: Pfizer Inc: 2015.
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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