Landmark Taxotere® Study in Early Stage Breast Cancer Published in the New England Journal of Medicine
Bridgewater, NJ
June 02, 2005
Earlier use of TAXOTERE®-based therapy shows improved long-term survival and
reduced chance of recurrence

The sanofi-aventis Group announced today that the New England Journal of Medicine has published the results of a landmark phase III study that demonstrates that an adjuvant (after surgery) TAXOTERE® (docetaxel) Injection Concentrate-based regimen showed a significant 28 percent reduction in risk of relapse (p=0.001) and a significant 30 percent reduction in the risk of death (p=0.008) after 55 months of follow-up in women with operable, node-positive breast cancer. The results were observed regardless of the nodal, hormone-receptor, menopausal and HER-2/neu status.

Conducted by the Breast Cancer International Research Group (BCIRG), this large, multi-center trial (BCIRG 001/ TAX 316) involved nearly 1,500 patients from around the world.  The study analysis included all the women (intent-to-treat group) who were treated with either TAC (TAXOTERE® with doxorubicin and cyclophosphamide) after surgery or with a standard adjuvant regimen known as FAC (5-fluorouracil, doxorubicin and cyclophosphamide). 

“What is particularly important about the TAXOTERE® findings is that the risk of relapse is reduced in both hormone receptor positive and hormone receptor negative patients and is irrespective of the number of positive lymph nodes, which means that all women with operable, node-positive breast cancer may potentially benefit from the TAC therapy,” said Dr. Miguel Martin, Hospital Clínico San Carlos, Madrid- Spain, President of the GEICAM (Grupo Español de Investigación en Cáncer de Mama), and member of the BCIRG steering committee. 

TAXOTERE® is the only FDA approved drug in the taxane class with an established disease-free survival benefit in both hormone receptor positive and negative disease.

This is the first time these results have been published; however, these findings were presented at the 26th San Antonio Breast Cancer Symposium (SABCS) in 2003.  

“In this study, 87 percent of women treated in the TAXOTERE® arm were alive at five years versus 81 percent in the arm without TAXOTERE®.  The data from the study suggest that by substituting TAXOTERE® for 5-fluorouracil after surgery, we now have a treatment that may be able to benefit more women with early stage breast cancer,” said John R. Mackey, MD, FRCP(C), Co-Chair of the study, Department of Oncology, University of Alberta, and Cross Cancer Institute, Edmonton, Canada.

“These results provide hope for women with node positive early breast cancer,” said Dr. Jean-Paul Guastala, anti cancer centre Léon Berard, Lyon-France, and co-chair of the study. “With TAXOTERE®, nearly nine out of ten women in this study are alive at five years compared to eight out of ten with the standard FAC regimen.”

TAXOTERE® in combination with doxorubicin and cyclophosphamide has received FDA and EMEA approval for the adjuvant treatment of patients with operable node-positive breast cancer.

About the BCIRG 001 / TAX 316 Study
The primary endpoint of this multi-center study was to compare the disease-free survival after treatment with TAXOTERE® in combination with doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan), (TAC), to a standard regimen of 5-fluorouracil, doxorubicin and cyclophosphamide, (FAC). 

The study enrolled 1,491 pre- and post-menopausal women with operable, node-positive breast cancer from 112 sites in 20 countries between June 1997 and June 1999. Women were randomized to receive either TAC or FAC in the adjuvant setting. 

Follow-up data (55 months) of women on the study did not identify unexpected side effects and confirmed the results already presented at the time of the first interim analysis (33 months).  Specifically, the TAC regimen was associated with a higher rate of febrile neutropenia (low white blood cell count that can lead to infections) compared with FAC (24.7 percent versus 2.5 percent).  However, incidence of severe infection was similar (3.9 percent versus 2.2 percent) and there were no treatment-related deaths due to infection in the study. Patients in the study were not treated with primary prophylactic G-CSF (granulocyte colony-stimulating factor), but G-CSF was required for subsequent cycles following the first episode of febrile neutropenia and/or infection. An antibiotic prophylaxis was systematically administered to all women treated with TAC.

Other severe adverse events occurring in 5 percent or more of patients treated with TAC included neutropenia, nausea, stomatitis and asthenia, and with FAC included neutropenia, nausea, vomiting and asthenia. 

More than 90 percent of patients in both treatment groups received all six cycles of treatment. 

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 cancer mortality reason in women of 40 to 59 years old.

More than one million new cases of breast cancer are reported worldwide annually and more than 400,000 women die each year from the disease. 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.  In the United States, breast cancer will represents this year more than 215,000 new cases and 40,000 will die. With earlier screening and diagnosis, early management of patients may offer better chances of survival.

Indications and Usage 
Breast Cancer

TAXOTERE® is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy.

TAXOTERE® in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer.

IMPORTANT SAFETY INFORMATION

WARNING: TAXOTERE® 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® should not be given to patients with low white–blood-cell counts, abnormal liver function, or a history of allergic reactions to TAXOTERE® or any of the ingredients in TAXOTERE®. 

Before each TAXOTERE® treatment, all patients treated with TAXOTERE® must receive another medicine called dexamethasone.  This drug can help reduce the risk of fluid retention (edema) and allergic reactions.
 
TAXOTERE® 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® 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® 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®. Women of childbearing potential should avoid becoming pregnant during treatment with TAXOTERE®.

Before receiving TAXOTERE®, tell your doctor if

  • You have any allergies
  • You are taking any other medicines — including nonprescription (over-the-counter) drugs, vitamins, and dietary or herbal supplements

When taking TAXOTERE®, contact your doctor if

  • You have symptoms of an allergic reaction (warm sensation, tightness in your chest, itching/hives, or shortness of breath)
  • You experience any other side effects

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®, visit www.taxotere.com or see full prescribing information including boxed WARNING.  For more information about ongoing clinical trials, please call 1-800-RxTrial or visit www.aventisoncology.com.

 

About sanofi-aventis

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 (NYSE: SNY)

Forward Looking Statements
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The sanofi-aventis Group conducts its business in the United States through its subsidiaries Sanofi-Synthélabo Inc., Aventis Pharmaceuticals Inc. and Sanofi Pasteur Inc.

 

U.S. Contact
Marisol Peron, 908-243-7592, marisol.peron@sanofi-aventis.com