First Phase III study performed solely in high risk node-negative population to show significant improvement in Disease Free Survival (DFS)

BRIDGEWATER, N.J., May 27 /PRNewswire-FirstCall/ -- Sanofi-aventis and GEICAM (Grupo Espanol de Investigacion en Cancer de Mama) announced today that for women with high-risk node-negative early stage breast cancer adjuvant treatment (post surgery) with Taxotere(R) (docetaxel) Injection Concentrate as part of the TAC regimen (Taxotere(R), doxorubicin, cyclophosphamide) was associated with a significant improvement in Disease Free Survival (DFS) compared to a standard FAC regimen (5-Fluorouracil, doxorubicin, cyclophosphamide) in the GEICAM 9805/Target-0 study.

The results will be presented at the 2008 annual meeting of the American Society of Clinical Oncology, ASCO, in Chicago (Monday June 2, 2008, 2-6 pm, poster number 1D, abstract 542).

In Europe and North America, most breast cancer patients are diagnosed at an early stage, before the tumor has spread to the lymph nodes. However, few clinical trials in the past were dedicated exclusively to this population of patients. GEICAM 9805/Target-0 is the first taxane-based study to exclusively enroll women with node-negative early stage breast cancer considered to be at high risk for recurrence. High risk patients were defined as having at least one of the following St Gallen 1998 criteria: patient's age <35 years, tumor histological grade II/III, tumor size >2 cm, or hormone-receptor (estrogen and/or progesterone receptor) negative tumor.

The 1059 women enrolled in this multicenter, phase III study were randomized to receive either TAC (n=539) or FAC (n=520) after surgical resection of their tumor. Therapy was given every three weeks for a total of 6 cycles. The primary end point was Disease Free Survival (DFS) and secondary end points included overall survival (OS), safety, and quality of life.

Analysis of efficacy, determined by DFS, was performed after a minimum of 5-years of follow up. The study showed a significant improvement in 5-year DFS that was demonstrated in the TAC arm over the FAC arm, with 91% and 86% patients, respectively, alive and disease free (HR 0.66, 95% CI 0.46-0.94, p=0.0202). The OS data are immature; estimated 5-year OS is 97% for TAC and 95% for FAC (HR 0.72, 95% CI 0.40-1.30, p=0.2677). The safety results have been already published (Martin et al (2006), Ann Oncol 17: 1205-12) TAC produced significantly more hematological adverse reactions than FAC. Primary prophylaxis with G-CSF reduced the rate of neutropenic fever. No toxic deaths were reported.

"First of all, I would like to congratulate the patients and my fellow investigators for having the courage to participate in this innovative trial in a purely node-negative patient population. This study showed that the TAC regimen improves Disease Free Survival in women with high risk node-negative breast cancer," said GEICAM Chair and principal investigator of the 9805 study, Prof. Miguel Martin.
 

About the Study

The GEICAM 9805/Target-0 trial was initiated as a complementary study to BCIRG 001/TAX 316, a study that enrolled women with node-positive early stage breast cancer.

From December 2001 to March 2003, 1059 patients aged 18-71, with T1-T3, N0, M0 operable breast cancer and at least one high-risk St Gallen 1998 criterion (patient age <35 years, tumor grade II/III, tumor size >2 cm, or hormone-receptor negative tumor) were enrolled in the study; 1047 patients were eligible. Patients from Spain as well as Germany and Poland were stratified by institution and menopausal status and randomized after surgery to receive either TAC (docetaxel 75 mg/m2, doxoru bicin 50 mg/m2, cyclophosphamide 500 mg/m2) or FAC (5-fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2) every 3 weeks for 6 cycles. Radiotherapy was mandatory after conservative surgery and recommended for patients with tumors > 5 cm; tamoxifen was given for 5 years to all patients with endocrine responsive tumors. A study amendment initiated during enrollment mandated the use of G-CSF with the first cycle of TAC, in order to reduce the incidence and severity of hematological toxicities and febrile neutropenia.

The primary end-point was DFS with analysis planned after a minimum follow-up of 5 years.
The full safety analysis has previously been published (Martin et al (2006), Ann Oncol 17: 1205-12). The analysis demonstrated that febrile neutropenia (grade 4) was the most common and clinically severe event
(24.6%) reported with the TAC regimen. The incidence of febrile neutropenia decreased to 6.5% with the use of G-CSF from the first cycle of TAC. The incidence of febrile neutropenia among patients treated with FAC was 2.3%. Grade 2-4 anemia was higher in the TAC regimen (47.4%) vs FAC (7.5%). The incidence of anemia TAC decreased (27.5%) with the use of G-CSF. No toxic deaths were reported.

About Breast Cancer
 

According to the American Cancer Society, worldwide, breast cancer is the most common cancer in women and the second most common after lung cancer in both genders. 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.

In Europe, breast cancer is responsible for 27.3% of all new cancer cases among women and 20.22% of cancer deaths. The International Agency for Research in Cancer estimates that in 2004 there were 360,749 new breast cancer cases diagnosed while the number of deaths was 129,013.

According to the American Cancer Society, in general, breast cancer rates have risen about 30% in the past 25 years in western countries. In addition, the incidence is highest in western countries. This appears to be due to increased screening which detects breast cancer in earlier stages.

About GEICAM

GEICAM (Grupo Espanol de Investigacion en Cancer de Mama) is a Spanish non-profit scientific cooperative group fully devoted to breast cancer. GEICAM is comprised of oncologists who belong to the Spanish Society of Medical Oncology (SEOM) and of other health professionals related to breast cancer research and treatment. The main GEICAM objectives are to promote basic, epidemiological and clinical research, and to provide education to
doctors and patients and dissemination of information in the field of breast cancer to the Spanish general population.

About sanofi-aventis

Sanofi-aventis, a leading global pharmaceutical company, discovers, develops and distributes therapeutic solutions to improve the lives of everyone. Sanofi-aventis is listed in Paris (EURONEXT PARIS: SAN) and in New York (NYSE: SNY).

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