Sanofi-aventis and GEICAM (Grupo Español de Investigacion en Cancer de Mama) announced that for women with high-risk node-negative early stage breast cancer adjuvant treatment (post surgery) with Taxotere (docetaxel) Injection Concentrate as part of the TAC regimen (Taxotere, 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), a sanofi-aventis press release stated.
In Europe and North America, most breast cancer patients are diagnosed at an early stage, before the tumour 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 enrol 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, tumour histological grade II/III, tumour size >2 cm, or hormone-receptor (estrogen and/or progesterone receptor) negative tumour.
The 1059 women enrolled in this multi-centre, phase III study were randomized to receive either TAC (n=539) or FAC (n=520) after surgical resection of their tumours. 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 5 years follow up. The study showed a significant improvement in DFS that was demonstrated in the TAC arm over the FAC arm, with 91% and 86% patients, respectively, alive and disease free at 5 years (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 published (Martin et al (2006), Ann Oncol 17: 1205-12). TAC produced significantly more haematological 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.
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, tumour grade II/III, tumour size >2 cm, or hormone-receptor negative tumour) 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, doxorubicin 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 tumours > 5 cm; tamoxifen was given for 5 years to all patients with endocrine responsive tumours. A study amendment initiated during enrolment mandated the use of G-CSF with the first cycle of TAC, in order to reduce the incidence and severity of haematological toxicities and febrile neutropenia. The primary end-point was DFS with analysis planned after a minimum follow-up of 5 years.