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Herceptin with Chemotherapy Improves Survival in
Early Stage Breast Cancer
Dec. 9, 2005 - Pairing the targeted therapy Herceptin with chemotherapy in patients with early stage breast cancer
significantly increases disease-free survival time in women who test
positive for a genetic mutation that results in a particularly
aggressive form of the disease, according to large, international study.
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The study also tested Herceptin with a chemotherapy
combination that eliminated Adriamycin, an anthracycline commonly used
to treat breast cancer but a drug that, when used with Herceptin, can
result in heart damage. That regimen also significantly improves
survival.
Conducted by the Breast Cancer International
Research Group (BCIRG), this study is the fourth large clinical trial to
show that Herceptin plus chemotherapy significantly reduces risk of
disease recurrence in early breast cancer.
Results were presented Thursday at the San Antonio
Breast Cancer Symposium by Dr. Dennis Slamon, co-chairman of BCIRG,
director of Clinical/Translational Research at UCLA's Jonsson Cancer
Center and the scientist whose laboratory and clinical research laid the
groundwork for the development of Herceptin.
"The chemotherapy combinations we tested with
Herceptin proved to be superior to the best available standard therapy
for early breast cancer," said Slamon, principal investigator for the
BCIRG study. "This further illustrates the promise of targeted therapies
and moves us closer to our goal of minimizing the toxicity of therapy
while maximizing efficacy."
Herceptin is effective in women with HER-2 positive
breast cancer, about one in four diagnosed with the disease every year.
HER-2 positive breast cancer patients have a particularly aggressive
form of the disease, a poorer prognosis and shorter survival times, said
Slamon, who discovered the link between HER-2 positivity and aggressive
breast cancer in 1987.
The study enrolled 3,222 women from all over the
world with early stage HER-2 positive breast cancer between March 2001
and February 2004. Patients received one of three regimens:
* The standard therapy of Adriamycin and Carboplatin followed by
Taxotere (ACT).
* An experimental regimen of Adriamycin and Carboplatin followed by
Taxotere and one year of Herceptin (ACTH).
* An experimental regimen of Taxotere and Carboplatin with one year of
Herceptin (TCH).
Reduction in risk of disease recurrence, the
study's primary endpoint, was 51 percent in the ACTH study arm and 39
percent in the TCH arm.
"This is very promising news for the 250,000 women
worldwide, including 50,000 in the United States, who will be diagnosed
every year with this aggressive breast cancer," Slamon said.
The BCIRG study also resulted in two other
important findings. Researchers knew that giving Herceptin with
Adriamycin resulted in heart damage in some patients, the most severe of
which was congestive heart failure. It was theorized, however, that this
damage was not long lasting. But the BCIRG study showed the cardiac
toxicity was significant and still persisted for more than 18 months at
the date of the last follow up, Slamon said. This is vital information
for doctors and patients to have when deciding which treatment regimen
to use.
Of the 3,222 patients in the study, 353 experienced
a greater than 10 percent loss of heart function. Of those, 91 patients
(9 percent) were enrolled in the ACT study arm; 82 patients (8 percent)
were in the TCH arm; and 180 patients (17.3 percent) were in the ACTH
arm, which paired Adriamycin with Herceptin.
"We've always known that the major safety problem
with Herceptin has been cardiac toxicity when it is used with
Adriamycin," Slamon said. "When breast cancer patients lose their hair,
it grows back. When we suppress their bone marrow, that comes back, too.
Heart failure, however, is a much larger problem, especially if it does
not improve over time."
The good news, Slamon said, is that Herceptin given
with the chemotherapy combination that eliminates Adriamycin is still
significantly superior to the best available chemotherapy alone,
reducing risk of relapse by 39 percent. That gives physicians and
patients worried about heart damage an additional option.
The study's other important finding is that a
subset of HER-2 positive patients - about 35 percent - also have
amplification of a gene called topo II, which makes them more likely to
respond to Adriamycin. As Herceptin targets HER-2, Adriamycin targets
topo II. Patients who test positive for amplification of both HER-2 and
topo II might opt for the drug regimen with Adriamycin, risking heart
damage in exchange for a better response to therapy.
Slamon said a test that indicates both HER-2 and
topo II amplification is being developed so doctors will better be able
to tell which patients should be on which drug regimen.
"Women will have the information they need to
decide if the risk is worth the benefit," Slamon said.
At UCLA's Jonsson Cancer Center, doctors are
testing Herceptin in combination with other targeted therapies such as
the angiogenesis inhibitor Avastin. That, Slamon said, may be the future
of breast cancer therapy - the elimination of chemotherapy.
"In the future, we're likely to come up with
therapies that are very much improved over what we have now and offer
maximum efficacy with little or no toxicity," Slamon said.
UCLA's Jonsson Comprehensive Cancer Center
comprises more than 240 researchers and clinicians engaged in research,
prevention, detection, control, treatment and education. One of the
nation's largest comprehensive cancer centers, the Jonsson center is
dedicated to promoting research and translating the results into
leading-edge clinical studies. In July 2005, the Jonsson Cancer Center
was named the best cancer center in the western United States by U.S.
News & World Report, a ranking it has held for six consecutive years.
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