Multicenter, randomized phase III study of adjuvant chemotherapy for high-risk, node-negative breast cancer comparing tac with fac: 5-year efficacy analysis of the GEICAM 9805 trial

Abstract

542 Background: Adjuvant docetaxel improves disease-free survival (DFS) and overall survival (OS) in node-positive breast cancer (BC) patients (pts). However, most BC pts at diagnosis are node-negative, and the role of taxanes in such pts is not established. Methods: Pts aged 18–70, with T1-T3, N0, M0 operable BC and at least one high-risk St Gallen 1998 criterion (grade II/III, size >2 cm, age <35 years, hormone-receptor [HR] negative) were eligible. Pts were stratified by institution and menopausal status and randomized to either TAC (docetaxel 75 mg/m², doxorubicin 50 mg/m², cyclophosphamide 500 mg/m²) or FAC (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 pts with tumors > 5 cm. Tamoxifen was given for 5 years to all pts with HR-positive tumors. The primary endpoint was DFS defined as BC recurrence, second primary malignancy including contralateral BC, or death from any cause, whichever occurred first. Primary analysis is planned with 5-yr minimum follow-up (f/u). Results: Between July 1999 and December 2001, 1,059 pts were randomized (TAC 539, FAC 520) with 1,047 (98.9%) evaluable. Median age was 50 (TAC) vs 49 years (FAC), with 55% premenopausal in both arms; other characteristics were balanced between arms. Treatment compliance and toxicity have been reported (Martin et al, Ann Oncol 17: 1205). TAC produced significantly more hematologic toxicity than FAC, although primary prophylaxis with G-CSF reduced the rate of neutropenic fever. No toxic deaths were reported. As of June 7, 2007 (median f/u 6 years), 128 pts experienced a DFS event (TAC: 52 pts, FAC 76 pts) with estimated 5-year DFS of 91% for TAC and 86% for FAC (HR 0.66, 95% CI 0.46–0.94, p=0.0202). With 45 deaths (TAC: 19 pts, FAC: 26 pts), the estimated 5-year OS is 97% for TAC and 95% for FAC (HR 0.72, 95% CI 0.40–1.30, p=0.2677). Conclusions: For pts with high-risk node-negative BC, adjuvant TAC was associated with a significant improvement in DFS compared with FAC, with manageable toxicity. Updated results will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis