Monday, May 18, 1998
-- First Monoclonal Antibody to Fight Metastatic Breast Cancer Slows the Progression of Cancer and Causes Tumor Shrinkage --
LOS ANGELES -- May 18, 1998 -- Genentech, Inc. (NYSE:GNE) today announced at the annual meeting of the American Society of Clinical Oncology (ASCO) Phase III investigational clinical trial results for Herceptin (Trastuzumab), a humanized anti-HER2 monoclonal antibody intended for the treatment of women with metastatic breast cancer who have tumors that overexpress the growth factor receptor HER2. Results showed Herceptin when used in combination with chemotherapeutic agents slows the progression of cancer and increases tumor shrinkage in HER2-overexpressing patients compared to HER2-overexpressing patients receiving only chemotherapy.
If Herceptin, designated as a Fast Track Product by the U.S. Food and Drug Administration (FDA), is approved by the FDA, it will be the first potential treatment for HER2-overexpressing metastatic breast cancer, an aggressive form of the disease that is associated with more rapid cancer progression and shortened survival. It is the first therapy that was developed by Genentech to target a specific protein defect that contributes to the malignant progression of cancer. HER2 overexpression occurs in 25 to 30 percent of patients with breast cancer.
"The final Phase III trial results of Herceptin are exciting because the data show that women who overexpress HER2 may be helped with this potential new monoclonal antibody for the treatment of metastatic breast cancer, an aggressive disease," said Dennis Slamon, M.D., University of California, Los Angeles School of Medicine and a principal investigator of Herceptin.
"Genentech submitted its Biologics License Application to the FDA for Herceptin on May 4, and we are continuing to work as rapidly as possible in coordination with the FDA to seek approval and to make Herceptin available to women who could benefit from this novel therapy," said Arthur Levinson, Ph.D., Genentech's president and chief executive officer.
The Phase III investigational comparison trial evaluated time to disease progression and safety as the primary endpoints. Patients were treated either with Herceptin in combination with chemotherapy -- paclitaxel alone or anthracycline plus cyclophosphamide -- or treated with chemotherapy alone. The study included 469 women who had tumors that overexpressed HER2 who had not been previously treated with chemotherapy for their metastatic disease.
Trial results showed that patients treated with Herceptin and chemotherapy experienced tumor progression later than patients treated with chemotherapy alone. The median time to disease progression was increased by 65 percent (from 4.6 to 7.6 months). Approximately 28 percent of women treated with Herceptin plus chemotherapy did not show evidence of tumor progression at one year compared to 14 percent of the women treated with chemotherapy alone.
Adding Herceptin to chemotherapy also increased the number of women who had a complete or partial response (or tumor shrinkage of 50 percent or greater) from 32 percent (74 of 234 patients) to 49 percent (114 of 235), a 53 percent increase. Clinical benefits were observed in patients who received Herceptin in combination with both anthracyclines and paclitaxel, but were greater with paclitaxel. In the Herceptin-plus-anthracycline group, 52 percent (75 of 143) of women had a response, compared to 43 percent (59 of 138) in patients receiving anthracyclines alone. In the Herceptin-plus-paclitaxel group, 42 percent (39 of 92) of women had a response, compared to 16 percent (15 of 96) in patients receiving paclitaxel alone. Finally, the median duration of response in responders, measured from the time the cancer responds to treatment to the time when the cancer begins to enlarge or spread again, was over 9 months in the Herceptin group compared to less than 6 months in the chemotherapy group alone.
Herceptin Alone Trial
The second large investigational clinical trial evaluated the overall response rate and safety as primary endpoints when using Herceptin as a single agent (without chemotherapy). The study included 222 women with HER2-overexpressing metastatic breast cancer who had relapsed disease following treatment with one or two prior chemotherapy regimens for metastatic disease. Ninety-four percent (202 of 214) of patients had prior anthracycline therapy and 26 percent (53 of 205) received bone marrow transplants.
The overall response rate assessed by the Response Evaluation Committee (REC) was 16 percent (34 of 213) with eight patients experiencing a complete response (4 percent) and 26 experiencing a partial response (12 percent). The median duration of response was 9 months.
"Since therapy is rarely curative for end stage breast cancer and life expectancy is limited, today's treatments are primarily palliative," said Melody Cobleigh, M.D., Rush-Presbyterian-St. Luke's Medical Center, and a principal investigator of Herceptin. "A 16 percent response rate and 9 month duration of response is particularly interesting given the seriousness and aggressive
nature of metastatic breast cancer. Patients could potentially have another option that is active as a single agent and maintain the women's quality of life while on therapy. The lack of toxicity is impressive."
Herceptin generally was well tolerated among the more than 450 patients treated with Herceptin in both trials. Overall, the most common adverse events related to Herceptin were chills and fever in approximately 40 percent of patients, primarily with the first infusion. Side effects -- including hair loss, mouth sores, and low blood cell count levels, which occur often in women receiving chemotherapy -- were not seen commonly among women taking Herceptin alone.
An increased risk of cardiac dysfunction was observed in women receiving Herceptin and anthracyclines at the same time compared to women receiving anthracyclines alone. In the Herceptin-plus-anthracycline group, 27 percent (38 of 143) of women experienced cardiac dysfunction, compared to 6 percent (8 of 135) in patients receiving anthracyclines alone. The incidence of cardiac dysfunction was 12 percent (11 of 91) for Herceptin and paclitaxel compared to 2 percent (2 of 95) in patients receiving paclitaxel alone. In patients treated with Herceptin alone the incidence was 4.7 percent (10 of 213). This side effect can be potentially severe or life-threatening, but in most cases can be managed with medication. Most of these patients (87 percent) had symptomatic improvement with initial treatment for their cardiac dysfunction. Of the 38 patients with cardiac dysfunction receiving Herceptin plus anthracyclines 14 continued, and of the 11 patients receiving Herceptin plus paclitaxel 6 continued without further cardiac events.
Overall, death or severe disability due to cardiac dysfunction occurred in about 1 percent of the more than 900 patients treated with Herceptin in all clinical trials.
The Importance of HER2 Testing
In 1985, the HER2 growth factor receptor was identified and researchers began to understand the role HER2 overexpression plays in the progression of breast cancer. This increased understanding led to the development of Herceptin as a possible means of combating this devastating form of the disease.
Nearly a third of women with breast cancer have tumors that overexpress HER2. Women with breast cancer have not been routinely screened for HER2 overexpression because currently there is not a treatment that targets this condition directly.
"HER2 overexpressing breast cancers are different and need to be treated differently than less aggressive cancers," said Dr. Slamon. "Because HER2 is a known marker for faster growing, more serious disease, it will be critical that effective HER2 testing be integrated into diagnostic and treatment guidelines."
The Prevalence of Breast Cancer
Approximately 1.6 million women have been diagnosed with breast cancer in the United States. 180,000 new cases are diagnosed in any given year, according to the American Cancer Society. Genentech estimates there are approximately 164,000 women with metastatic breast cancer. Of these women, 25-30 percent have tumors that overexpress HER2 and may be candidates for this potential therapy.
Genentech, Inc. is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Eleven of the currently marketed biotechnology products stem from Genentech science, six of which Genentech markets directly in the United States. The company has headquarters in South San Francisco, California and is traded on the New York Stock Exchange and the Pacific Exchange under the symbol GNE.
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