Thursday, Dec 14, 2006
South San Francisco, Calif. -- December 14, 2006 --Genentech, Inc. (NYSE: DNA) today announced results from the second interim analysis of BCIRG 006, a Phase III study evaluating Herceptin® (Trastuzumab) plus chemotherapy in early-stage HER2-positive breast cancer, as well as a final analysis of TAnDEM, a Phase III trial studying Herceptin plus the hormone therapy anastrozole in hormone receptor-positive, HER2-positive metastatic breast cancer. In addition, data from 170 studies evaluating Herceptin-based treatment regimens in a variety of settings and disease stages, including preliminary Phase II data of Herceptin in combination with Avastin® (bevacizumab) in HER2-positive metastatic breast cancer, will be presented at the 29th San Antonio Breast Cancer Symposium.
"The studies being presented at this year's San Antonio meeting add to the growing body of knowledge on Herceptin across all stages of HER2-positive breast cancer,"said David Schenkein, M.D., vice president, Clinical Hematology and Oncology at Genentech. "Genentech is committed to understanding Herceptin's full potential in treating women with the earliest to the most advanced stages of this aggressive disease."
Phase III BCIRG 006 Study:
Dennis Slamon, M.D., of the UCLA Jonsson Comprehensive Cancer Center, presented updated interim results from a randomized multicenter three-arm Phase III study, which compared doxorubicin and cyclophosphamide followed by Taxotere (AC-T) versus doxorubicin and cyclophosphamide followed by Taxotere and Herceptin (AC-TH) versus Taxotere, carboplatin and Herceptin (TCH), in more than 3,000 patients with early-stage HER2-positive breast cancer.
This study demonstrated that adding Herceptin to Taxotere following AC chemotherapy, or adding Herceptin to Taxotere and carboplatin chemotherapies, resulted in improved disease-free survival compared to chemotherapy alone. In addition, an analysis of overall survival in patients followed for a median of 36 months showed, in the AC-TH arm, a 41 percent reduction in the risk of death (based on a hazard ratio of 0.59, which is equivalent to a 69 percent improvement in overall survival), compared to the AC-T arm. The TCH arm showed a 34 percent reduction in the risk of death (based on a hazard ratio of 0.66, which is equivalent to a 52 percent improvement in overall survival), compared to the AC-T arm.
The BCIRG 006 trial is the fourth Herceptin adjuvant study to show that the addition of Herceptin to chemotherapy improved disease-free survival in patients with HER2-positive breast cancer. The study also explored these important areas of research for Herceptin:
The rate of clinically significant congestive heart failure (weakening of the heart muscle) in the non-anthracycline TCH arm was similar to the control arm of AC-T (0.4 percent in both arms). Congestive heart failure occurred at a rate of 1.9 percent in the AC-TH arm.
The international study was supported by Sanofi-aventis and Genentech, and conducted by the Breast Cancer International Research Group (BCIRG).
Phase III TAnDEM Study:
John R. Mackey, M.D., of the University of Alberta, presented data from TAnDEM, a randomized Phase III clinical trial that evaluated patients whose tumors were both hormone receptor-positive and HER2-positive. HER2-positive breast cancer occurs in approximately 25 percent of women with breast cancer, and about half of these patients with HER2-positive breast cancer also have tumors that are hormone receptor-positive.
This study is the first to suggest Herceptin plus an aromatase inhibitor improved progression-free survival (PFS) in patients with hormone receptor-positive, HER2-positive metastatic breast cancer, compared to those patients who received an aromatase inhibitor alone. Median PFS, the primary endpoint of the trial, in the Herceptin plus anastrozole arm (n=103) was 4.8 months compared to 2.4 months in the anastrozole alone arm (n=104), a 100 percent improvement.
Side effects in both the anastrozole alone and Herceptin plus anastrozole arms of the TAnDEM trial were consistent with those seen in previous individual clinical trials of Herceptin and anastrozole. The most commonly observed adverse events in patients receiving Herceptin plus anastrozole were fatigue, diarrhea, vomiting, fever, nausea, and nasopharyngitis. Thirteen of 103 patients in the Herceptin plus anastrozole arm experienced cardiac dysfunction (i.e., asymptomatic CHF, symptomatic CHF, myocardial infarction or heart attack, ischemia or restricted blood flow to the heart and dysrhythmia or irregular heart contractions), compared to two of 104 patients in the anastrozole alone arm.
Phase II Herceptin + Avastin Study:
Research suggests that the overexpression of both the HER2 protein and vascular endothelial growth factor (VEGF) is associated with poor clinical outcomes in breast cancer patients. On Friday, December 15, Mark Pegram, M.D., of the UCLA Jonsson Comprehensive Cancer Center, will present interim safety and efficacy data from a Phase II study evaluating the combination of Herceptin, which targets the HER2 protein, and bevacizumab, which targets VEGF, as first-line treatment in patients with HER2-positive breast cancer.
Herceptin is a targeted therapeutic antibody treatment for women who have tumors that overexpress the human epidermal growth factor receptor 2 (HER2) protein. HER2-positive breast cancer is an especially aggressive form of the disease that affects approximately one-fourth of women with breast cancer. Research has shown that women with HER2-positive breast cancer have a greater likelihood of recurrence, poorer prognosis and decreased survival compared to women with HER2-negative breast cancer. Special testing is required to identify women who have HER2-positive breast cancer and who may be candidates for treatment with Herceptin.
Herceptin is the only targeted biologic therapy approved for treatment of HER2-positive breast cancer in the adjuvant and metastatic settings. Herceptin first received FDA approval in September 1998 for use in women with metastatic breast cancer. In this setting, it is indicated for treatment of patients both as a first-line therapy in combination with paclitaxel and as a single agent in second- and third-line therapy. In November 2006, Herceptin was FDA-approved as part of a treatment regimen containing doxorubicin, cyclophosphamide, and paclitaxel for the adjuvant treatment of HER2-positive node-positive breast cancer based on results that showed Herceptin reduced the risk of cancer recurrence by 52 percent. Adjuvant therapy is given to women with early-stage (localized) breast cancer who have had initial treatment — surgery with or without radiation therapy — with the goal of reducing the risk of cancer recurrence and/or the occurrence of metastatic disease.
In clinical trials of HER2-positive metastatic breast cancer patients, Herceptin in combination with chemotherapy (paclitaxel) was the first anti-HER2 agent to demonstrate an improvement in survival in a Phase III trial. In December 2001, Genentech received FDA approval to include, in the product label, data that showed an improved median overall survival for women with HER2-positive metastatic breast cancer treated initially with Herceptin and chemotherapy, compared to chemotherapy alone (median 25.1 months compared to 20.3 months).
Herceptin Safety Profile
Herceptin administration can result in left ventricular dysfunction and congestive heart failure (CHF). The incidence and severity of left ventricular cardiac dysfunction/CHF were highest in patients who received Herceptin concurrently with anthracycline-containing chemotherapy regimens.
Herceptin should be discontinued in patients receiving adjuvant therapy for breast cancer who develop a clinically significant decrease in left ventricular function. In patients with metastatic breast cancer who develop a clinically significant decrease in left ventricular function, discontinuation of Herceptin should strongly be considered.
Serious infusion reactions and pulmonary toxicity have occurred; rarely these have been fatal. Discontinuation of Herceptin should be strongly considered for infusion reactions manifesting as anaphylaxis, angioedema, pneumonitis, or acute respiratory distress syndrome.
Exacerbation of chemotherapy-induced neutropenia has also occurred.
The most common adverse reactions associated with Herceptin use were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea (shortness of breath), rash, neutropenia (decrease in the number of neutrophils, a type of white blood cell), anemia, and myalgia (muscle pain).
Founded 30 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes biotherapeutics for significant unmet medical needs. A considerable number of the currently approved biotechnology products originated from or are based on Genentech science. Genentech manufactures and commercializes multiple biotechnology products and licenses several additional products to other companies. The company has headquarters in South San Francisco, Calif., and is listed on the New York Stock Exchange under the symbol DNA. For additional information about the company, please visit http://www.gene.com.
For full prescribing information, including Boxed WARNINGS for Herceptin, please call 800-821-8590 or visit http://www.gene.com.