Phase III Trail Comparing TAC (docetaxel, dosorubicin, cyclophosphamide) with FAC (5-fluorouracil, doxorubicin, cyclophosphamide) in the adjuvant treatment of node positive breast cancer (BC) patients: interim analysis of the BCIRG 001 Study

Reviewer: Mary Kara Bucci, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: May 19, 2002

Presenter: J-M Nabholtz
Presenter's Affiliation: Breast Cancer International Research Group (BCIRG)
Type of Session: Scientific


    Doxorubin and cyclophosphamide, with or without 5-fluorouracil, are standard chemotherapy agents in the adjuvant treatment of node positive breast cancer. Taxanes are a novel class of chemotherapeutic agents with both in vivo and clinical activity in a variety of cancers. Docetaxel, one of the taxanes, has been shown to be safe and effective for breast cancer in the metastatic setting. This trial directly compares a combination regimen including docetaxel to the standard treatment in a randomized fashion. This report is the planned 3-year interim analysis, with the primary end-point of disease-free survival, and secondary end-points of overall survival, toxicity, quality of life, and prognostic significance of pathologic/molecular markers.

Materials and Methods

  • Following standard surgical therapy, including either breast-conservation therapy (BCT) with lumpectomy and radiation, or mastectomy (with or without post-mastectomy radiation depending on the institutional policy), patients with positive lymph nodes were randomized to adjuvant therapy of either TAC or FAC.
  • Eligible patients had axillary lymph node dissections with at least 6 nodes dissected.
  • TAC was 75 mg/m2 docetaxel, 50 mg/m2 doxorubin, and 500 mg/m2 cyclophosphamide, given every three weeks for 6 cycles.
  • FAC was 500/50/500 mg/m2, respectively, on an identical schedule.
  • 745 patients were randomized to the TAC arm and 746 to the FAC arm.
  • Patient groups were well balanced with respect to number of positive lymph nodes, tumor size, type of surgery (BCT or mastectomy), addition of radiation, number of lymph nodes dissected, hormone receptor positivity, Her2 positivity, patient age and menopausal status.


  • 91% of patients on the TAC arm and 96% of patients of the FAC arm completed all 6 cycles of chemotherapy.
  • 100% of patients are evaluable with a median follow-up of 33 months.
  • Disease-free survival (DFS)is significantly higher in the TAC arm (84%) than the FAC arm (74%). This is statistically significant, with a p-value of 0.0011.
  • Overall survival (OS) was significantly improved 92% v. 87%, p=0.049.
  • DFS, when adjusted for hormonal status, was sigficantly improved in both ER/PR postive patients [relative risk (RR)of 0.66, p=0.005] and ER/PR negative patients (RR of 0.68, p=0.02).
  • When adjusted for Her2 status, DFS was again significantly improved in the TAC arm for both groups, RR 0.076, p=0.06 for Her2 negative, RR 0.59, p=0.02 for Her2 positive patients.
  • DFS adjusted for nodal status was as follows: for patients with 1-3 positive nodes, 96% v. 89%, RR 0.05, p=0.006; for patients with 4 or more positive nodes, 86% v. 84% DFS, RR 1.08, p=0.75.
  • Myelosuppression was significantly higher in the TAC arm, 65% v. 49% in the FAC arm.
  • Febrile neutropenia was also higher in the TAC arm, 24% v. 2%.
  • Infection rates were 3.1% in the TAC arm vs. 1.5% in the FAC arm. No septic deaths occurred on either arm.
  • Congestive heart failure was 1.2% on the TAC arm and 0.1% on the FAC arm.

Author's Conclusions

  • TAC conferred a statistically significant benefit in disease-free survival, with a 32% overall risk reduction (p=0.0011). Patients with 1-3 positive lymph nodes had a risk reduction of 54% (p=0.02).
  • The next planned analysis of this trial will be at 5 years. This additional follow-up will provide additional information on the role of TAC as adjuvant therapy for node positive breat cancer.

Clinical/Scientific Implications

    The benefit in disease-free survival, a primary end-point of this analysis, was statistically and clinically significant. This benefit was most pronounced in patients with 1-3 positive lymph nodes, and did not appear to depend on either hormone receptor or Her2 status. TAC may become an acceptable standard therapy for patients with node positive breast cancer if these data hold up over time. The efficacy of docetaxel in combination with doxorubicin and cyclophosphamide, as compared to paclitaxel, another taxane, in combination with these two agents, continues to be evaluated in an on-going Phase III trial.

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