Wednesday, Mar 14, 2001

Study Published in New England Journal of Medicine Demonstrates Herceptin with Chemotherapy Increases Median Survival in Women with Metastatic Breast Cancer

24 Percent Increase in Median Overall Survival Experienced by Women with HER2 Positive Disease when Herceptin and Chemotherapy Used First-line

South San Francisco, Calif. -- March 14, 2001 --

Genentech, Inc. (NYSE: DNA) today announced that women with one of the most aggressive forms of metastatic breast cancer experienced a significant survival benefit when treated initially with Herceptin® (Trastuzumab) and chemotherapy, compared to women treated with chemotherapy alone.

The findings, published in today's New England Journal of Medicine, are based on the final results of a pivotal trial in women with HER2 (human epidermal growth factor receptor2) positive metastatic breast cancer -- a fast-growing and deadly form of the disease with approximately half the life expectancy of women with HER2 negative breast cancer.

A supplemental Biological License Application (sBLA) has been submitted to the U.S. Food and Drug Administration (FDA) to add the median overall survival data to the Herceptin package insert.

"Herceptin represents a turning point in the treatment of breast cancer. The study results demonstrate that this targeted biologic approach is an important new treatment modality for metastatic breast cancer," said Dennis J. Slamon, M.D., Ph.D., the study's lead author and chief of the Division of Hematology and Oncology at UCLA's Jonsson Comprehensive Cancer Center. "These results confirm that Herceptin with chemotherapy used as a first-line therapy offers women with HER2 positive metastatic breast cancer their best chance at increasing survival."

In an accompanying editorial Elizabeth A. Eisenhauer, M.D., of Queen's University, Kingston, Ontario, called the Herceptin study by Dr. Slamon and his colleagues a "landmark trial," and she concluded, "This is the beginning of an important new era in cancer treatment since many more targeted therapies are now undergoing clinical evaluation."

Larry Norton, M.D., the study's senior author and head, Division of Solid Tumor Oncology at Memorial Sloan-Kettering Cancer Center commented: "The exciting results of this prospective, randomized study demonstrate the value of clinical trials in translating important laboratory observations into actual therapies that extend and save lives."

Study Results

Final results from this pivotal Phase III trial of 469 women showed that those treated weekly with Herceptin and standard cycles of chemotherapy (anthracycline and cyclophosphamide (AC) or paclitaxel) as a first-line therapy had a 24 percent increase in median overall survival -- almost five months (median 25.1 months compared to 20.3 months) -- as compared to women treated with chemotherapy alone.

In this pivotal trial the increased efficacy with Herceptin was observed in both Herceptin plus chemotherapy subgroups. The combination of Herceptin and chemotherapy compared to chemotherapy alone improved the overall response rate from 32 percent to 50 percent, prolonged the time to disease progression (TTP) from 4.6 to 7.4 months and increased median duration of response from 6.1 to 9.1 months.

"Publication of the final results of the pivotal trial in a peer-reviewed journal is an important milestone for Herceptin," said Susan D. Hellmann, M.D., M.P.H., Genentech's executive vice president, Development and Product Operations and chief medical officer. "Herceptin is one of only a few therapies to demonstrate this type of survival benefit for metastatic breast cancer. These results further underscore the importance for women with breast cancer and their physicians of understanding the aggressive nature of HER2 driven disease."

Herceptin generally was well tolerated by the women in the study. Overall, the most common adverse events were fever, hematologic toxicity and cardiac dysfunction. Infusion-associated signs and symptoms were observed but did not require antibody discontinuation. In the post-marketing setting, rare serious and fatal infusion-related events have occurred. Most patients who experienced the more serious and fatal infusion-related events had pre-existing pulmonary compromise and advanced malignancy.

The most serious adverse event was cardiac dysfunction (NYHA Grade I-IV), which occurred more frequently when Herceptin was administered with AC (27 percent) compared with AC alone (8 percent), or with Herceptin plus paclitaxel (13 percent) compared to paclitaxel alone (1 percent). Although the NYHA Grade III/IV toxicity, which occurred in a smaller percentage of patients, was potentially severe and/or life threatening, signs and symptoms improved in 75 percent of patients and none of the patients receiving paclitaxel had persistent Grade III/IV cardiac dysfunction with medical management. Continued use of Herceptin was not associated with further cardiac deterioration in most patients. The only significant risk factor associated with this adverse event was advanced age.

Herceptin is approved by the FDA for the treatment of women with HER2 positive metastatic breast cancer both as first-line therapy in combination with paclitaxel and as a single agent in second-and third-line therapy. Herceptin is not approved for use with AC.

"Cardiac safety is important when considering the use of Herceptin," said Dr. Slamon. "However, given the extremely poor clinical prognosis of women with HER2 positive disease and the fact that it is essentially incurable with current regimens, the risk of cardiac dysfunction must be weighed against the potential significant clinical benefit of Herceptin therapy when used within indication."

New Herceptin Studies

Four Phase III randomized clinical trials evaluating Herceptin as adjuvant therapy in early-stage breast cancer currently are enrolling or planning to enroll more than 10,000 patients at 800 sites worldwide.

Three of these trials are being conducted by leading cooperative groups, including the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Breast Cancer International Research Group (BCIRG), and the North Central Cancer Treatment Group (NCCTG). The latter is an InterGroup study open to institutions from the Southwest Oncology Group (SWOG), Eastern Cooperative Oncology Group (ECOG) and the Cancer and Leukemia Group B (CALGB). The fourth trial will be conducted outside the United States by F. Hoffmann-La Roche.

Women with breast cancer or caregivers interested in learning more about the Herceptin adjuvant trials should speak to their physicians and/or call the National Cancer Institute's (NCI) Cancer Information Service (CIS) at 1-800-4-CANCER, or they can visit NCI's clinical trials website at http://www.cancer.gov/clinicaltrials. Additionally, women interested in the BCIRG trial can call 514-748-3940 or email contact@BCIRG.com.

"The next step is to see if the beneficial effects of Herceptin are seen in patients newly diagnosed with breast cancer with abnormal amounts of HER2," said Dr. Norton.

"This is a critical focus of ongoing and planned clinical trials."

About Breast Cancer

Approximately 1.6 million women have been diagnosed with breast cancer in the United States. According to the American Cancer Society, 180,000 new cases are diagnosed in any given year. Genentech estimates there are approximately 164,000 women with metastatic breast cancer.

About Herceptin

Herceptin received FDA approval in September 1998 for use in women with HER2 positive metastatic breast cancer. The genetic alteration in the HER2 gene produces an increased amount of the growth factor receptor protein on the tumor cell surface that can be inhibited with the administration of Herceptin in patients with HER2 positive disease. Routine tumor marker testing in women with breast cancer is critical for identification of patients who are HER2 positive and who potentially could benefit from treatment with Herceptin. Herceptin is marketed in the United States by Genentech and internationally by Roche.

Genentech, Inc., is a leading biotechnology company that discovers, develops, manufactures and markets human pharmaceuticals for significant unmet medical needs. Fourteen of the currently marketed biotechnology products stem from Genentech science, nine 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 under the symbol DNA.

For full prescribing information please call (650) 225-8681. For more information, please visit http://www.gene.com.

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