Results from the BCIRG 006 study also show that a novel non-anthracycline-based regimen ("TCH") with TAXOTERE(R) (docetaxel), the platinum salt carboplatin and HERCEPTIN(R) (trastuzumab) reduces the risk of recurrence without increasing cardiotoxicity in patients with early stage HER2-positive breast cancer
SAN ANTONIO, Dec. 8 /PRNewswire-FirstCall/ -- The Breast Cancer International Research Group (BCIRG) and the sanofi-aventis Group today announced the results from the first interim efficacy and updated safety analyses from the BCIRG 006 Phase III breast cancer study, which show that HERCEPTIN(R) combined with TAXOTERE(R)-based regimens significantly improved disease free survival for women with early HER2-positive breast cancer. This data was presented at the 28th annual San Antonio Breast Cancer Symposium (SABCS) in San Antonio, TX - USA.
Cardiac and global safety data together with the interim efficacy analysis based on 322 events were reviewed by an Independent Data Monitoring Committee (IDMC). The relative reduction in the risk of relapse were: 51% [95% CI: 35%-63%], p-value of < 0.001 and 39% [95% CI: 21%-53%], p-value of <0.001 for the AC-TH and TCH arms, respectively, when compared to the control arm of AC- T. There was no statistically significant difference between the 2 HERCEPTIN(R) -containing experimental arms. Overall survival data is not yet mature.
"These results confirm, that in this trial, a disease-free survival benefit was seen in the adjuvant setting with the addition of HERCEPTIN(R) to either of two TAXOTERE(R)- containing chemotherapy regimens, with or without doxorubicin, in this poor prognosis population of women with HER2 positive breast cancer," said Dennis Slamon, PhD, MD, Co-Chair of the BCIRG 006 study and Director of Clinical and Translational Research at UCLA's Jonsson Comprehensive Cancer Center. "Moreover, additional molecular studies in patients from the BCIRG 006 study identified a subgroup (approximately 35%) of HER2-positive patients receiving Herceptin which may have a superior response to doxorubicin-based versus non-doxorubicin-based therapies."
The BCIRG 006 study was designed to evaluate how to potentially maximize efficacy of HERCEPTIN(R)-based therapy in the adjuvant treatment of HER2- positive breast cancer, while minimizing toxicity. The novel concept of using a non-anthracycline containing regimen in the early breast cancer setting derives from preclinical research.
The study enrolled a total of 3,222 women with early-stage HER2 positive breast cancer between March 2001 and February 2004 and is now closed to accrual. BCIRG continues to closely monitor patients for long-term efficacy and safety analyses.
Women eligible for study participation were randomized to receive one of the following three treatment arms after primary surgery and lymph node sampling:
Doxorubicin has been considered a standard agent in early breast cancer therapy for over 25 years. Women whose tumors contain the HER2 alteration, as first described by Slamon (UCLA) in 1987, have a much more aggressive form of the disease. In the original FDA registration trial for the HER2-targeted biologic agent HERCEPTIN(R) (in first-line metastatic breast cancer), a significant increase in heart failure occurred, particularly when it was administered in combination with doxorubicin. Consistent with the objective of maximizing efficacy while minimizing toxicity, the purpose of the adjuvant BCIRG trial is twofold; to determine if the introduction of HERCEPTIN(R) in early stage HER2-positive breast cancer significantly improves clinical outcomes for patients, and to determine if the increased cardiotoxicity seen with the combination of HERCEPTIN(R) and doxorubicin could be avoided by using a novel, non-anthracycline-containing regimen, namely "TCH", which had previously demonstrated activity in preclinical models.
Protocol-defined cardiac events unique to the BCIRG 006 study included grade 3 or 4 arrhythmias and ischemia/myocardial infarction. Common to all of the HERCEPTIN(R) adjuvant trials was the incidence of congestive heart failure and sudden death. BCIRG 006 protocol-defined events occurred at the following rates: 0.9% in the AC-T arm, 2.6% in the AC-TH arm, and 1.0% for the TCH arm. The incidence of clinical heart failure occurred at a rate of 0.19% (2 pts), 1.8% (10 pts) and 0.09% (1 pt) in the AC-T, AC-TH and TCH arms, respectively.
A total of 306 patients experienced a > 10% relative asymptomatic decrease in left ventricular ejection fraction (LVEF), as follows: 91 pts (9%) in the AC-T arm, 180 pts (17.3%) in the AC-TH arm and 82 pts (8%) in the TCH arm. Contrary to what was previously thought, the majority of patients treated with a doxorubicin-based therapy experienced a sustained loss in LVEF over time (> 550 days at the date of this analysis). In addition, a mixed model analysis of ejection fraction showed a statistically significant (p<0.001) decline in LVEF for both doxorubicin-containing arms AC-T and AC-TH, but not for TCH. The BCIRG 006 study data demonstrated that the vast majority of the TCH declines recovered fully.
"The BCIRG 006 trial is a testament to the courage of the 3,222 patients and hundreds of investigators who made these results possible. These data demonstrated the significant benefit of adding molecular targeted therapy, directed against the HER-2 oncoprotein to TAXOTERE(R) in the adjuvant treatment of breast cancer," said Dr. John Crown, head of Medical Oncology Research, St. Vincent's University Hospital, Dublin, Ireland.
The study was sponsored by sanofi-aventis, had financial support from Genentech, and was conducted by BCIRG.
About Breast Cancer
Breast cancer is the most frequently diagnosed cancer in women. It is the second-leading cause of cancer death in women after lung cancer, and since 1990 is increasing predominantly in women 50 and over. It is the first cause of cancer mortality in women of 40 to 59 years old. According to the American Cancer Society, an estimated 211,240 women will be diagnosed with breast cancer and approximately 40,000 women will die of the disease in the United States in 2005. A woman is diagnosed with breast cancer in the United States every three minutes. The risk of a woman developing breast cancer during her lifetime is approximately 13 percent (about one in seven of all women in the United States). In the European Union, more than 191,000 new cases are diagnosed each year and more than 60,000 women will die. Of women with breast cancer, 20 to 25% of these women will have HER2 positive breast cancers. With earlier screening and diagnosis, early management of patients may offer better chances of survival.
BCIRG is the breast cancer division of the Cancer International Research Group (CIRG). CIRG has performed a number of new and innovative clinical trials with new cancer therapies. Active participation by its network of dedicated leaders and investigators has made CIRG the success it is today. The organization is dedicated to bringing rational and innovative therapeutic concepts into the clinical trial setting through translational approaches based on the underlying biology of the disease. To further this objective, CIRG will be merging with Translational Oncology Research International (TORI), founded by Dr. Dennis Slamon. TORI is a smaller clinical trials group directly linked to several basic research laboratories in which new therapeutic molecules are evaluated.
CIRG has offices located in Paris (France) and Edmonton Alberta (Canada).
For information about CIRG/BCIRG, please visit their website: WWW.CIRG.ORG Contact:
TAXOTERE(R) is currently approved in the United States to treat patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy, and it is also approved in combination with doxorubicin and cyclophosphamide (TAC regimen) for the adjuvant (post surgery) treatment of patients with operable, node-positive breast cancer.
TAXOTERE(R) is approved for the treatment of patients with unresectable locally advanced or metastatic non-small cell lung cancer (NSCLC) in combination with cisplatin, who had not received prior chemotherapy, and it also is approved for patients with unresectable locally advanced or metastatic NSCLC after failure of prior platinum-based chemotherapy. In addition, the U.S. Food and Drug Administration has approved TAXOTERE(R) for use in combination with prednisone as a treatment for men with androgen-independent (hormone-refractory) metastatic prostate cancer.
Important safety information
WARNING: TAXOTERE(R) treatment can cause serious, physically limiting, and potentially life-threatening side effects, such as infection, low blood-cell counts, allergic reaction, and retention of excess fluid (edema).
TAXOTERE(R) should not be given to patients with low white-blood-cell counts, abnormal liver function, or a history of allergic reactions to TAXOTERE(R) or any of the ingredients in TAXOTERE(R).
Before each TAXOTERE(R) treatment, all patients treated with TAXOTERE(R) must receive another medicine called dexamethasone. This drug can help reduce the risk of fluid retention (edema) and allergic reactions.
TAXOTERE(R) should be administered only under the supervision of a qualified physician experienced in the use of anticancer treatments. Appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available.
Treatment-related acute myeloid leukemia (AML) has occurred in patients given anthracyclines and/or cyclophosphamide, including use with TAXOTERE(R) in adjuvant therapy for breast cancer.
The most common severe side effects are low white-blood-cell count, anemia, fatigue, diarrhea, and mouth and throat irritation. Low white-blood- cell count can lead to life-threatening infections. The earliest sign of infection may be fever, so tell your doctor right away if you have a fever.
Other common side effects from TAXOTERE(R) include nausea, vomiting, hair loss, rash, infusion-site reactions, odd sensations (such as numbness, tingling, or burning) or weakness in the hands and feet, nail changes, muscle and/or bone pain, or excessive tearing.
Patients 65 years of age or older may experience some side effects more frequently than younger patients.
Because of the potential risk of fetal harm, pregnant women should not receive TAXOTERE(R). Women of childbearing potential should avoid becoming pregnant during treatment with TAXOTERE(R).
Please see adjacent page for patient information leaflet for detailed information about these side effects, and talk to your doctor about any questions you may have.
For more information about TAXOTERE(R), visit http://www.taxotere.com/ or see accompanying full prescribing information including boxed WARNING. For more information about ongoing clinical trials, please call 1-800-RxTrial or visit http://www.aventisoncology.com/.
The sanofi-aventis Group is the world's third largest pharmaceutical company, ranking number one in Europe. Backed by a world-class R&D organization, sanofi-aventis is developing leading positions in seven major therapeutic areas: cardiovascular, thrombosis, oncology, metabolic diseases, central nervous system, internal medicine, and vaccines. The sanofi-aventis Group is listed in Paris (EURONEXT: SAN) and in New York
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