Abstract P5-10-05: A Phase III Adjuvant Randomized Trial of 6 Cycles of 5-Fluorouracil - Epirubicine-Cyclophosphamide (FEC100) Versus 4 FEC 100 Followed by 4 Taxol (FEC-T) in Node Positive Breast Cancer Patients (Trial B2000)

The risk of relapse after local therapy remains unacceptable for the majority of patients with early stage breast cancer. Adjuvant chemotherapy has been shown to prolong both disease-free survival (DFS) and overall survival. Several large phase III trials addressing the benefit of adding a taxane to conventional anthracycline-based regimen in early breast cancer showed a significant improves DFS in node-positive breast cancer patients. Taxane-based regimen seems to be more toxic in terms of myelosuppression. There seem to be fewer cardiac events after the taxane-based regimen attributable to the lower anthracycline cumulative dose. Therefore, the optimal adjuvant treatment in node positive breast cancer is still debated and several attempts are made to identify the patients, who will benefit most of taxane. The primary end point of this phase III randomized trial was to compare chemotherapy with 6 cycles of FEC 100 versus 4 cycles of FEC 100 followed by 4 cycles of Taxol, in patients with non-metastatic breast cancer with lymph node invasion (N+), in terms of DFS assessed by Kaplan-Meier analysis. The secondary end-points were overall survival (OS), local recurrence free interval, metastases free interval and tolerance. Material and Methods Between 10.3.2000 and 31.12.2002, 837 patients with invasive non-metastatic N+ breast cancer were randomized between (arm A) epirubicine 100 mg/m 2 plus 5FU 500 mg/m 2 plus cyclophosphamide 500 mg/m 2 every 3 weeks (w) (FEC) for 6 cycles (417 patients) or (arm B) FEC every 3 w for 4 cycles then taxol 175 mg/m 2 every 3 w for 4 cycles (FEC-T) (420 patients). Hormone-receptor-positive patients received either tamoxifen or anti-aromatize depending of their menopausal status, for 5 years after chemotherapy. Results The patients’ characteristics were well balanced between the 2 arms. The mean number of N+ was 4.5. Seventy-three % of the patients had oestrogen receptor positive (RO+) and 62 % progesterone receptor positive (RP+). The hazard ratio for DFS was 0.986 (95% confidence limits 0.773 — 1.257, P = 0.91). Five-year DFS rates were 78.5% with FEC and 78.4% with FEC-T. Nine-year DFS rates were 62.9% with FEC and 62.5% with FEC-T. The hazard ratio for OS was 0.848 (95% confidence limits 0.622 — 1.155, P = 0.29). The 5-y-OS was 86.1 % with FEC and 88.6 % with FEC-T) and the 9-y-OS was 73.9 % and 77 % respectively. The incidence of grade 3 to 4 neutropenia, infection, and nausea were higher with FEC without reaching significativity, neurotoxicity and hypersensitivity reactions were more frequent with FEC-T. There was no statistical difference in cardiac toxicity and febrile neutropenia between the 2 arms. Conclusion The final results of this trial suggest that adding taxol (every 3 weeks regimen) to an anthracycline-based regimen in patients with non-metastatic breast cancer with lymph node invasion (N+), confers little advantage in terms of DFS and OS. However, the present trial was powered to detect a 30% reduction in the risk of recurrence or death. A meta-analysis of all similar trials is needed to rule out smaller differences that could still be clinically worthwhile. This trial was supported by BMS Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-05.