|New Study of Targeted Therapies for Breast Cancer Establishes Model for Global Clinical Trials
Two targeted medications designed to treat an aggressive form
of breast cancer are being tested in a new study involving 8,000
participants in 50 countries across six continents — a clinical
trial that investigators hope will provide a new model for global
cancer research. This trial, dubbed ALTTO (Adjuvant Lapatinib and/or
Trastuzumab Treatment Optimization study), will be one of the first
global initiatives in which two large, academic breast cancer research
networks covering different parts of the world have jointly developed
a study in which all care and data collection are standardized,
regardless of where patients are treated. The networks are The
Breast Cancer Intergroup of North America (TBCI), based in the
United States, and the Breast International Group (BIG) in Brussels,
Belgium. TBCI consists of six National Cancer Institute (NCI)-funded
clinical trials cooperative groups. NCI is part of the National
Institutes of Health.
ALTTO is designed to answer the most pressing questions regarding
use of two widely used cancer agents: whether one agent is more
effective, which agent is safer for patients, and what benefit
will be derived by taking the drugs separately, in tandem order,
or together? The trial is a randomized, Phase III study,
which is considered a gold standard method for proving drug effectiveness.
two agents tested in ALTTO are drugs designed to treat HER2-positive
tumors, which is a particularly aggressive form of cancer that
affects approximately 20 percent to 25 percent of breast cancer
patients. Both agents, trastuzumab (Herceptin) and lapatinib (Tykerb),
have already been approved by the U.S. Food and Drug Administration
for use for treatment of HER2-positive breast cancer. ALTTO
will provide the first head-to-head comparison of trastuzumab and
lapatinib in the earliest, most treatable stages of cancer. It
will also be one of the first large-scale studies to evaluate lapatinib's
effectiveness in treating early breast cancer.
HER2-positive breast cancer is caused by an excess of HER2 genes
or by over-production of its protein, the HER2 cell surface receptor.
Trastuzumab consists of large antibodies that once injected into
patients, latch on to the portion of the HER2 protein that sits
on the outer surface of the cancer cell whereas lapatinib acts
by entering a cancer cell and binding to the part of the HER2 protein
that lies beneath the surface of the cell.
trial is unusual in that it has two different designs depending
on whether patients with stage I or stage II breast cancer have
already been treated with chemotherapy. The study thus will
compare four different regimens of targeted therapy administered
over a 52-week period. Patients will be randomized to receive either
trastuzumab or lapatinib alone, or trastuzumab followed by lapatinib,
or the two treatments in combination.
"There have been major improvements in the management of
patients with early breast cancer in the last few years, so this
new study builds on this knowledge and sets an example of the new
era: good science, good worldwide collaboration," said Edith
Perez, M.D., an oncologist in the North Central Cancer Treatment
Group (NCCTG) at Mayo Clinic in Jacksonville, Fla., who will lead
the study for TBCI. "It may be that using two treatments
that work in different ways against HER2-positive breast cancer
offers a complementary strategy that is more powerful than either
will be one of the first trials of its scope in which translational
research — taking science from bench to bedside — plays a critical
role, investigators say. In ALTTO, biological material will be
collected from thousands of patients in order to determine a tumor
profile that responds best to the drugs — information that
could lead to individualized patient care and, possibly, to development
of next generation agents.
difference between this study and many that came before it is that
the collection of biological materials occurs as the trial is being
conducted, not as an afterthought. While there are exceptions,
not many companies or organizations have been willing to invest
in that kind of research before," said Martine J. Piccart,
M.D., Ph.D., professor of oncology at the Université Libre
de Bruxelles, Belgium, and lead investigator for BIG, which she
founded in 1996. "Now we have the chance to optimize
therapy with powerful drugs in order to provide the best treatment
possible for each of our patients."
and Piccart led the development team of the ALTTO trial and will
act as the study's co-principal investigators. On behalf
of BIG and TBCI, these two lead investigators have been working
toward collaborative clinical studies for a number of years. The
ALTTO study, they say, represents a new paradigm that blends the
high standards of both systems in order to test the latest breast
cancer treatments as efficiently as possible in thousands of women
NCI greatly appreciates the work that Mayo Clinic, TBCI and BIG
are doing to help advance our understanding of the complex mechanisms
that underlie different types of breast cancer," said Jo
Anne Zujewski, M.D., a senior investigator in the clinical investigations
branch at NCI. "We hope that this model of international
collaboration is one which we can build upon in the future."
in combination with the chemotherapy drug capecitabine, was approved
by the U.S. Food and Drug Administration in March 2007 for the
treatment of advanced or metastatic HER2-positive breast cancer
in patients who had received prior therapy with three agents —
an anthracycline, a taxane and Herceptin. GlaxoSmithKline is providing
the study drug, as well as additional financial support for the
ALTTO trial. All drugs carry potential side effects, and more information
of side effects for lapatinib and trastuzumab can be found in the
Q&A at http://www.cancer.gov/newscenter/pressreleases/ALTTOQandA.
NCI and GSK also provided comment and input on the design of the
will act as the treatment base for ALTTO in North America. BIG
is a network of 41 non-U.S. research groups from around the world. Its
Brussels-based BrEAST Data Center is providing centralized data
management for the global study (including the United States). The
other members of TBCI include the Eastern Cooperative Oncology
Group (ECOG), the Cancer and Leukemia Group B (CALGB), the Southwest
Oncology Group (SWOG), the
American College of Surgeons Oncology Group (ACOSOG),
and the National Cancer Institute of Canada Clinical Trials Group
date, more than 300 centers around the world have enrolled patients
into ALTTO. Full enrollment is expected to involve about 500 centers
in the United States and more than 800 centers in Europe and the
rest of the world. A complete listing of ALTTO participating
sites can be found by searching for ALTTO at http://clinicaltrials.gov.
A Science Writer's seminar on International Breast Cancer
Trials and ALTTO will take place on Friday, February 29, 2008 in
New York City. To register for the seminar, please call (301)
496-6641 or go to www.videocast.nih.gov to
view a Webcast of the event.
For Broadcasters: Video soundbites from the lead investigators
are available through Pathfire's Digital Media Gateway (DMG)
or on the Web at www.TheNewsMarket.com. On
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For a Q&A on this trial, please go to http://www.cancer.gov/newscenter/pressreleases/ALTTOQandA.
For Spanish translations of the press release and Q&A, please
go to http://cancer.gov/espanol/noticias/ALTTOSpanishRelease.
For more info on BIG, please go to http://www.breastinternationalgroup.org.
For more info on Mayo, please go to http://clinicaltrials.mayo.edu or
contact the Mayo Clinic Cancer Center Clinical Trials Referral
Office at 507-538-7623.
For more information about cancer, visit http://www.cancer.gov,
or call NCI's Cancer Information Service at 1-800-4 CANCER.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.