CONTACT: TOM MOORE
8798 John Pappajohn Pavilion
Iowa City IA 52242
Release: Nov. 2, 2000
Women with early stage breast cancer sought to evaluate the benefit of
IOWA CITY, Iowa -- University of Iowa Health Care is partnering with the
National Surgical Adjuvant Breast and Bowel Project (NSABP), a network of
medical professionals funded by the National Cancer Institute (NCI), to launch
a new phase III clinical trial that will evaluate Herceptin (Trastuzumab)
in the adjuvant setting. Conducted at more than 100 sites across the United
States and Canada, Protocol B-31 will assess the safety and efficacy of the
combination of Herceptin and chemotherapy in the treatment of 2700 node-positive
breast cancer patients whose tumors over-express the HER2 (human epidermal
growth factor receptor-2) protein or demonstrate evidence of HER2 gene-amplification.
The HER2 gene (also referred to as erbB-2 or HER2/neu) produces a protein
that stimulates normal cell growth; however, it also seems to play a significant
role in the biology of breast cancer. Over-expression, or an abundance, of
the HER2 protein is found in about 25-30 percent of malignant breast tumors
and is associated with more aggressive cancer growth and shortened patient
survival. Based on this knowledge, researchers are now testing therapies that
are aimed at tumors with HER2 over-expression.
"Herceptin is on the forefront of biologic warfare against breast cancer,
and University of Iowa Health Care is excited to be on the front line bringing
these potential advancements to the women of Iowa," says Peter Jochimsen,
M.D., a surgical oncologist in the Holden Cancer Center at the UI. "The
results of this study may improve treatment for women with early stage breast
cancer tumors that over-express HER2, and we look towards the future with
Herceptin, a humanized monoclonal antibody, was approved by the U.S. Food
and Drug Administration (FDA) to treat women with metastatic breast cancer
whose tumors are known to have an over-expression of HER2. Previous research
has proven Herceptin's ability to target the HER2 receptor in metastatic breast
cancer, which tends to decrease the spread of the disease and prolongs patient
survival. In a pivotal clinical trial, women with HER2 positive metastatic
breast cancer who received Herceptin in combination with chemotherapy achieved
a 50 percent response rate compared to 32 percent for women receiving chemotherapy
alone. Women who received Herceptin in addition to chemotherapy lived longer
than those who received chemotherapy alone. Few therapies have demonstrated
this type of survival benefit in this patient population. In the NSABP B-31
trial, the role of Herceptin will be tested in women with breast cancers having
HER2 over-expression and whose tumors have spread to the axillary (underarm)
lymph nodes but not to other organs. They will be given either chemotherapy
alone or chemotherapy plus Herceptin.
"This trial is the first NSABP adjuvant phase III study to evaluate
a biologic agent like Herceptin in patients with operable breast cancer,"
says Elizabeth Tan-Chiu, M.D., NSABP associate director of medical oversight
and B-31's protocol officer. "We hope to learn whether the use of Herceptin
in this group of breast cancer patients can provide a major advancement when
added to the standard therapy of surgery, chemotherapy, and radiation therapy."
"Herceptin has demonstrated a survival advantage in women with HER2
positive metastatic breast cancer, a particularly aggressive form of the disease,
when combined with chemotherapy considered the standard of care," said
Gwen Fyfe, M.D., senior director of oncology at Genentech. "We believe
that the response seen with Herceptin in metastatic disease warrants further
study in the adjuvant breast cancer setting. We are pleased to be working
with the NSABP and University of Iowa Health Care on protocol
B-31 to evaluate the potential safety and efficacy of adding Herceptin to
chemotherapy for women with HER2 positive early stage breast cancer."
The side effects most commonly associated with Herceptin include fever and
chills, which are "infusion-related" reactions. They are generally
mild to moderate and treatable. These side effects usually occur shortly after
the drug's first administration and tend to disappear as therapy continues.
In some patients, previous research has shown that Herceptin alone, or in
combination with standard chemotherapy, can increase a patient's risk for
developing serious heart problems. As a result, B-31 was designed to closely
monitor patients for serious heart problems.
NSABP Protocol B-31 will be conducted in two stages. Stage 1 will evaluate
1,000 patients for cardiac safety and compare the toxicities of adding weekly
Herceptin to adjuvant Taxol following Adriamycin and cyclophosphamide (AC).
If researchers determine that the potential benefits of Herceptin therapy
are greater than the drug-related side effects, the study will proceed to
Stage 2. This second stage will accrue an additional 1,700 patients to study
the efficacy of adding Herceptin to the standard chemotherapy regimen (AC
followed by Taxol) in prolonging patient survival and disease-free survival.
In women with metastatic breast cancer, Herceptin may also be associated
with increased shortness of breath or reactions that are pulmonary in nature.
Rarely, these reactions can be severe or life threatening. Patients with pre-existing
lung disease or breast cancer that had spread to their lungs may be more susceptible
to these reactions. Since B-31 is designed to evaluate the potential safety
and efficacy of Herceptin in women with early stage breast cancer, these pulmonary
reactions are rarely expected to occur.
In B-31, patients will be randomly divided into two therapy groups after
balancing for the number of positive nodes, type of surgery (lumpectomy, mastectomy),
tamoxifen administration, and choice of radiotherapy. Both groups will receive
a total of eight cycles (1 cycle -- 1 treatment every 3 weeks) of therapy.
Group 1, the control group, will receive four cycles of 60 mg Adriamycin (doxorubicin)
and 600 mg of cyclophosphamide (AC) followed by four cycles of 175 mg Taxol
(paclitaxel). Group 2 will receive the same AC and Taxol therapy schedule
plus a weekly dose of Herceptin. Women in both groups whose tumors are estrogen-receptor-positive
(ER+) or progesterone-receptor-positive (PgR+) will also receive tamoxifen
(20 mg/day) for five years. Tamoxifen is optional for women whose tumors are
ER-negative or PgR-negative.
B-31 will enroll a total of 2,700 women over the next five years. UI Health
Care is currently enrolling women who have: 1) operable breast cancer treated
either with lumpectomy plus irradiation or mastectomy; 2) histologically positive
axillary nodes; 3) breast cancer with strong HER2 protein over-expression
determined either by immunohistochemistry (IHC) or Her2 gene amplification
in situ hybridization (FISH); and 4) no evidence of metastatic disease. Women
with existing heart disease are not eligible to participate.
Herceptin was discovered and developed and is manufactured and marketed
in the U.S. by Genentech. It is currently indicated as a first-line therapy
in combination with Taxol and alone as a second- and third-line therapy for
women with metastatic breast cancer who have tumors that over-express the
For more information on protocol B-31, please call UI Health Access at 800-777-8442
or call the U.S. National Cancer Institute's Cancer Information Service (CIS)
at 800-4-CANCER (800-422-6273) to locate a participating site near you. Additional
information can be obtained by visiting the NSABP's Web site at http://www.nsabp.pitt.edu
or NCI's clinical trials Web site at http://cancertrials.nci.nih.gov.
University of Iowa Health Care describes the partnership between
the UI College of Medicine and the UI Hospitals and Clinics and the patient
care, medical education and research programs and services they provide.