Extended benefit from sequential administration of docetaxel after standard fluorouracil, epirubicin, and cyclophosphamide regimen for node-positive breast cancer: the 8-year follow-up results of the UNICANCER-PACS01 trial

Abstract

Purpose: The initial report from the Programme Action Concertée Sein (PACS) PACS01 trial demonstrated a benefit at 5 years for disease-free survival (DFS) and overall survival (OS) rates with the sequential administration of docetaxel after FEC100 (fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), and cyclophosphamide 500 mg/m(2)) for patients with node-positive, operable breast cancer. We evaluate here the impact of this regimen at 8 years.

Patients and methods: Between June 1997 and March 2000, a total of 1,999 patients (age <65) with localized, resectable, non-pretreated, unilateral breast cancer were randomly assigned to receive either standard FEC100 for 6 cycles or 3 cycles of FEC100 followed by 3 cycles of 100 mg/m(2) docetaxel (FEC-D), both given every 21 days. Radiotherapy was mandatory after conservative surgery and tamoxifen was given for 5 years to hormone receptor (HR)-positive patients. Five-year DFS was the trial's main endpoint. Updated 8-year survival data are presented.

Results: With a median follow-up of 92.8 months, 639 patients experienced at least one event. A total number of 383 deaths were registered. Eight-year DFS rates were 65.8% with FEC alone and 70.2% with FEC-D. OS rates at 8 years were 78% with FEC alone and 83.2% with FEC-D. Cox regression analysis adjusted for age and number of positive nodes showed a 15% reduction in the relative risk of relapse and a 25% reduction in the relative risk of death in favor of FEC-D. Significant relative risk reductions were observed in the HR-positive, HER2-positive, and Ki67 ≥20% subpopulations.

Conclusion: Benefits for DFS and OS rates with the sequential FEC-D regimen are fully confirmed at 8 years.

Figure 1.

Kaplan-Meier 8-year estimates in the intent-to-treat population. (A): Disease-free survival rates were 65.8% with fluorouracil-epirubicin-cyclophosphamide (FEC) and 70.2% with fluorouracil-epirubicin-cyclophosphamide with docetaxel (FEC-D). (B): Overall survival rates were 78% with FEC and 83.2% with FEC-D. Abbreviations: D, docetaxel; DFS, disease-free survival; FEC, fluorouracil, epirubicin, and cyclophosphamide; HR, hazard ratio; ITT, intent-to-treat; OS, overall survival.

Figure 2.

Analysis of treatment effect by subgroups in the intent-to-treat population. Hazard ratios and 95% confidence intervals are reported in different subgroups (Forest plot analysis) for overall survival rates. Abbreviations: CI, confidence interval; D, docetaxel; ER, estrogen receptor; FEC, fluorouracil, epirubicin, and cyclophosphamide; HER2, human epidermal growth factor receptor 2; PR, progesterone receptor.

Figure 3.

Kaplan-Meier survival curves for overall survival rates are shown for the patient subgroups of (A) HER2-negative, (B) HER2-positive, (C) Ki67-negative, (D) Ki67-positive, (E) hormone receptor (HR)-positive with tamoxifen, and (F) HR-positive without tamoxifen. Abbreviations: D, docetaxel; FEC, fluorouracil, epirubicin, and cyclophosphamide; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; OS, overall survival.