Wednesday, Dec 11, 2002
San Antonio -- December 11, 2002 --Genentech (NYSE: DNA) and Roche (SWX Zurich) today announced preliminary positive results from a clinical study evaluating Herceptin® (Trastuzumab), paclitaxel and carboplatin in first-line HER2 (human epidermal growth factor receptor2) positive metastatic breast cancer patients. The randomized Phase III trial demonstrated that the addition of carboplatin to Herceptin and paclitaxel resulted in a six-month improvement in time to progression in patients scored 3+ by IHC, compared to the standard Herceptin and paclitaxel regimen. Results of this trial were presented at the San Antonio Breast Cancer Symposium by lead investigator Nicholas Robert, M.D., of Inova Fairfax Hospital, Fairfax, Virginia.
"This study shows that the addition of carboplatin may provide clinical benefit and demonstrates improvement in response rate and time to disease progression in HER2-positive metastatic breast cancer patients," said Dr. Robert. "In addition, the preliminary analysis of survival is encouraging. Median survival in the Herceptin and paclitaxel arm was 33.5 months and has not been reached at 36 months of follow-up in the Herceptin, paclitaxel and carboplatin arm."
The study (abstract # 35) enrolled 194 women who had evidence of HER2 protein overexpression by immunohistochemistry (IHC); 191 patients were evaluable for the primary endpoint of time to progression. Results of the randomized study showed that women receiving Herceptin, paclitaxel and carboplatin had a median time to progression of 11.2 months, compared to 6.9 months for those receiving standard treatment of Herceptin and paclitaxel alone. In women with IHC scores of 3+, those treated with all three agents had a median time to progression of 13.5 months, compared to 7.2 months in the group receiving Herceptin and paclitaxel. Investigators are in the process of retrospectively testing tumor samples in this study by FISH (fluorescence in-situ hybridization), a gene-based HER2 diagnostic test.
Researchers reported that the patients receiving the three-drug regimen experienced an increase in grade 3 and 4 neutropenia (55 percent vs. 27 percent) and thrombocytopenia (9 percent vs. 1 percent) compared to the group receiving Herceptin and paclitaxel. There was one case of cardiac dysfunction in the Herceptin/paclitaxel arm.
"Genentech's pivotal study with Herceptin and chemotherapy demonstrated significant clinical benefit compared to chemotherapy alone when Herceptin was given weekly until disease progression. We're pleased that the Herceptin/paclitaxel/carboplatin combination showed additional benefit in women with HER2-driven disease," said Gwen Fyfe, M.D., Genentech's vice president of Oncology, Medical Affairs. "This is important because patients with HER2-positive breast cancer have an aggressive form of the disease that is associated with more rapid cancer progression and shortened survival."
The pivotal Phase III Herceptin trial enrolled 469 patients with HER2 positive metastatic breast cancer, and randomized patients to receive Herceptin in combination with chemotherapy or chemotherapy alone. Trial results showed that patients treated with Herceptin and paclitaxel had a median time to progression of 6.7 months, compared to 2.5 months in the group receiving paclitaxel alone.
Herceptin is a targeted therapeutic antibody treatment that received FDA approval in September 1998 for use in patients with metastatic breast cancer who have tumors that overexpress the HER2 protein. It is indicated for treatment of patients both as first-line therapy in combination with paclitaxel and as a single agent in second- and third-line therapy. In clinical trials, Herceptin has shown a survival benefit when used as a first-line therapy in combination with chemotherapy given weekly until disease progression. Herceptin is marketed in the United States by Genentech and internationally by F. Hoffmann-LaRoche.
Herceptin Safety Profile
Herceptin therapy does involve risks. Serious side effects have occurred in patients treated with Herceptin.
Severe hypersensitivity reactions (including anaphylaxis), infusion reactions, and pulmonary events have been infrequently reported. Rarely, these were fatal. Serious reactions were treated by discontinuing Herceptin and administering supportive therapy. In clinical trials, the incidence and severity of cardiac dysfunction was highest in patients receiving Herceptin with anthracyclines. Most patients responded to medical therapy, including discontinuation of Herceptin. However, some patients were successfully managed while continuing Herceptin therapy. Patients receiving Herceptin should be monitored for deteriorating cardiac function.
In clinical trials, approximately 40 percent of patients experienced symptoms such as chills and fever during the first infusion. These and other symptoms, including nausea, vomiting, and pain, occurred infrequently with subsequent infusions. There was an increased incidence of anemia leukopenia,diarrhea, and infection when Herceptin was used in combination with chemotherapy.
Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. Fifteen of the currently approved biotechnology products originated from or are based on Genentech science. Genentech manufactures and commercializes ten biotechnology products 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.
Headquartered in Basel, Switzerland, Roche is one of the world's leading research-oriented healthcare groups with its two high-tech pillars, pharmaceuticals and diagnostics. Roche's innovative products and services address prevention, diagnosis, and treatment of diseases, thus enhancing people's well-being and quality of life.
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