"These findings show, when using Herceptin for the adjuvant treatment of women with HER2-positive, node-positive breast cancer, patients live longer," said Hal Barron, M.D., Genentech's senior vice president, Development and chief medical officer. "These data further reinforce the use of Herceptin and chemotherapy as the foundation of care for women with this aggressive form of the disease."
Edith Perez, M.D., director of Mayo Clinic's Multidisciplinary Breast Clinic in Jacksonville, Fla., presented these updated data from the joint analysis of NCCTG N9831 and NSABP B-31 (Abstract #512 -- Monday, June 4, 2007, 9 a.m. CDT) studying Herceptin in the adjuvant setting. 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.
These two randomized, controlled Phase III studies evaluated four cycles of doxorubicin and cyclophosphamide followed by paclitaxel, either every t hree weeks or weekly for 12 weeks, compared with the same regimens plus 52 weeks of Herceptin (beginning with the first dose of paclitaxel) in nearly 4,000 patients with HER2-positive breast cancer.
These results showed that the addition of Herceptin to standard adjuvant therapy continued to significantly reduce the risk of breast cancer recurrence, the primary endpoint of the studies, by 52 percent (based on a hazard ratio of 0.48) in women with HER2-positive, node-positive breast cancer, compared to patients who received standard adjuvant therapy alone. At four years of follow-up, 85.9 percent of women treated with Herceptin plus chemotherapy were disease free, compared to 73.1 percent of women treated with chemotherapy alone. The demonstrated treatment benefit of Herceptin plus chemotherapy was consistent across many important patient subgroups.
Notably, despite some patients crossing over to the Herceptin-containing arm, the additional follow-up data presented today showed an improvement in overall survival; 92.6 percent of women treated with Herceptin plus chemotherapy were still alive at four years of follow-up, compared with 89.4 percent of women treated with chemotherapy alone. This updated survival analysis showed a statistically significant 35 percent reduction in the risk of death (based on a hazard ratio of 0.65, p-value = 0.0007), which is equivalent to a 54 percent improvement in overall survival.
Each study had an independent external Data Monitoring Committee (DMC) that reviewed data from the studies, including cardiac safety data, on a regular basis. According to the investigators, serious or life-threatening (and in rare cases, fatal) cardiac events, most commonly congestive heart failure (weakening of the heart muscle), occurred approximately 3 to 4 percent more often in the Herceptin plus chemotherapy arms than in the chemotherapy alone arms. Other adverse events reported in both studies included dyspnea and interstitial pneu monitis, which occurred at a rate of less than 1 percent.
An update of cardiac function in patients enrolled in the NSABP B-31 trial presented by Priya Rastogi, M.D., of the University of Pittsburgh Cancer Institute (Abstract #513 -- Monday, June 4, 2007, 9:15 a.m. CDT), showed that the five-year cumulative incidence of cardiac events in the Herceptin-containing treatment arm was 3.8 percent, compared to 0.9 percent in the control arm. The cumulative incidence of cardiac dysfunction in the Herceptin arm remained stable, with no increase in cardiac events between year three and year five of follow-up, providing important insights into the long-term cardiac effects of Herceptin.
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 metastatic breast cancer, as a first-line therapy in combination with paclitaxel and as a single agent in second- and third-line therapy. In clinical trials of patients with HER2-positive metastatic breast cancer, Herceptin, in combination with chemotherapy (paclitaxel), was the first anti-HER2 agent to demonstrate an improvement in survival in a Phase III study. In December 2001, Genentech received FDA approval to inc lude, 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).
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.
There are now four studies in the adjuvant setting demonstrating that the addition of Herceptin to a chemotherapy regimen increased disease-free survival for women with early-stage HER2-positive breast cancer. Nearly 400,000 women have been treated with Herceptin worldwide since its first approval in 1998.
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. Physicians should discontinue Herceptin treatment in patients receiving adjuvant therapy for breast cancer and strongly consider discontinuation of Herceptin in patients with metastatic breast cancer who develop a clinically significant decrease in left ventricular function.
Patients receiving Herceptin should undergo frequent monitoring for deteriorating left ventricular function. More frequent monitoring should be employed in patients with preexisting cardiac dysfunction receiving Herceptin. Monitoring will not ident ify all patients who will develop cardiac dysfunction.
Serious infusion reactions and pulmonary toxicity have occurred; rarely these have been fatal. In most cases, symptoms occurred during or within 24 hours of administration of Herceptin. Herceptin infusion should be interrupted for patients experiencing dyspnea or clinically significant hypotension. Patients should be monitored until signs and symptoms completely resolve. 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 also has occurred.
The most common adverse reactions associated with Herceptin use were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia.
Please see full prescribing information for additional important safety information.
Founded more than 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.
Kimberly Ocampo, 650-467-0679 (Media)
Diane Schrick, 650-225-1599 (Investors)
Sara Chenault, 206-412-7593 (Advocacy)