Herceptin® Combined With Chemotherapy Improves Disease–Free Survival for Patients With Early–Stage Breast Cancer
Results from two large randomized clinical trials for patients
with HER-2 positive invasive breast cancer show that those patients
with early-stage breast cancer who received Herceptin® (trastuzumab)
in combination with chemotherapy had a significant decrease in
risk for breast cancer recurrence compared with patients who received
the same chemotherapy without trastuzumab. Patients are considered “HER-2
positive” if their cancer cells "overexpress," or
make too much of, a protein called HER–2, which is found
on the surface of cancer cells. Trastuzumab slows or stops the
growth of these cells, and it is only used to treat cancers that
overexpress the HER–2 protein. Approximately 20 percent to
30 percent of breast cancers overexpress HER-2. These tumors tend
to grow faster and are generally more likely to recur than tumors
that do not overproduce HER-2.
The clinical trials were sponsored by the National Cancer Institute
(NCI), part of the National Institutes of Health, and conducted
by a network of researchers led by the National Surgical Adjuvant
Breast and Bowel Project (NSABP) and the North Central Cancer Treatment
Group (NCCTG), in collaboration with the Cancer and Leukemia Group
B, the Eastern Cooperative Oncology Group, and the Southwest Oncology
Group. Genentech, Inc., South San Francisco, Calif., which manufactures
trastuzumab, provided the drug for the trials under the Cooperative
Research and Development Agreement (CRADA) with NCI for the clinical
development of trastuzumab.
The Data Monitoring Committees overseeing the combined analysis
of these trials (known as NSABP-B-31 and NCCTG-N9831)* recommended
that the results of a recent combined interim analysis be made
public because the studies had met their primary endpoints of increasing
disease-free survival (the amount of time patients live without
return of the cancer) in patients receiving trastuzumab in combination
with chemotherapy. The improvement in overall survival also was
statistically significant for women receiving a combination of
chemotherapy and trastuzumab.
Patients in the clinical trials who received trastuzumab in combination
with standard combination chemotherapy had a 52 percent decrease
in disease recurrence compared to patients treated with chemotherapy
alone. This difference is highly statistically significant. “This
is a major advance for many thousands of women with breast cancer,” said
NCI Director Andrew C. von Eschenbach, M.D. “These results
are one more example that we are at a major turning point in the
use of targeted therapies to eliminate suffering and death from
cancer,” he added.
The leaders of the studies underscored the significance of these
results and cited the collaborative efforts involved. “These
findings confirm that we now have a very potent weapon against
the recurrence of cancer cells that overexpress HER-2,” said
Edith A. Perez, M.D., who chaired the NCCTG trial and is a medical
oncologist at the Mayo Clinic in Jacksonville, Fla. “We gratefully
acknowledge the contribution of our co-investigators and, most
importantly, our courageous patients in helping to achieve these
unprecedented results.”
Edward Romond, M.D., study chair for the NSABP and professor of
oncology at the University of Kentucky, in Lexington, Ky., noted, “For
women with this type of aggressive breast cancer, the addition
of trastuzumab to chemotherapy appears to virtually reverse prognosis
from unfavorable to good.”
“These are truly life-saving results in a major disease,” said
JoAnne Zujewski, M.D., who oversees breast cancer trials for NCI’s
Cancer Therapy Evaluation Program. More detailed results from these
studies will be presented at the American Society of Clinical Oncology
(ASCO) annual meeting on May 16, 2005, in Orlando, Fla.
Information from over 3,300 patients enrolled in these studies
was used for analysis. Patients with operable breast cancer whose
tumors over-expressed HER-2 were enrolled in these studies between
February 2000 and April 2005. Patients were randomized to receive
chemotherapy with doxorubicin and cyclophosphamide followed by
paclitaxel, or doxorubicin and cyclophosphamide followed by paclitaxel
and trastuzumab. Most patients had lymph node-positive breast cancer,
or breast cancer that had spread to the lymph nodes, with only
a minority having lymph node-negative disease. The limited information
in the node-negative group did not allow for a separate analysis
of this group.
Chemotherapy of the type given in these studies has a risk of congestive
heart failure (weakening of the heart muscle) of less than 1 percent.
In these studies, the likelihood of congestive heart failure in
women receiving the combination of chemotherapy and trastuzumab
was increased by 3 percent to 4 percent. Patients in these studies
will continue to be followed for any additional side effects. Additional
safety data will be presented at ASCO.
Trastuzumab is an example of a “targeted” therapy
an agent that is directed against a specific change in the cancer
cell. Trastuzumab was approved for the treatment of advanced breast
cancer in 1998.
An estimated 211,240 women will be diagnosed with breast cancer
in the United States in 2005. Of these, about 30 percent have lymph
node-positive breast cancer, and about 20 percent to 30 percent
of these tumors overexpress the HER-2 protein, the target for trastuzumab.
Breast cancer is the most commonly diagnosed cancer in women and
the second leading cause of cancer-related death in women in this
country. An estimated 40,110 deaths from female breast cancer will
occur in 2005 in the United States, accounting for about 15 percent
of all cancer-related deaths in women in the nation.
For more information about cancer, please visit the NCI Web site
at http://www.cancer.gov or call NCI's Cancer Information Service
at 1-800-4 CANCER (1-800-422-6237).
* NSABP-B-31: Phase III Randomized Study of
Doxorubicin and Cyclophosphamide Followed By Paclitaxel With or Without
Trastuzumab (Herceptin®) in Women With Node-Positive Breast Cancer That Overexpresses
HER2
NCCTG-N9831: Phase III Randomized Study of Doxorubicin Plus Cyclophosphamide
Followed By Paclitaxel With or Without Trastuzumab (Herceptin® ) in Women
With HER-2-Overexpressing Node-Positive or High-Risk Node-Negative Breast
Cancer |