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Clinical Trial
. 2009 May 16;373(9676):1681-92.
doi: 10.1016/S0140-6736(09)60740-6.

Sequential Docetaxel as Adjuvant Chemotherapy for Early Breast Cancer (TACT): An Open-Label, Phase III, Randomised Controlled Trial

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Free PMC article
Clinical Trial

Sequential Docetaxel as Adjuvant Chemotherapy for Early Breast Cancer (TACT): An Open-Label, Phase III, Randomised Controlled Trial

Paul Ellis et al. Lancet. .
Free PMC article

Abstract

Background: Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment. The UK TACT study (CRUK01/001) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with standard chemotherapy of similar duration.

Methods: In this multicentre, open-label, phase III, randomised controlled trial, 4162 women (aged >18 years) with node-positive or high-risk node-negative operable early breast cancer were randomly assigned by computer-generated permuted block randomisation to receive FEC (fluorouracil 600 mg/m(2), epirubicin 60 mg/m(2), cyclophosphamide 600 mg/m(2) at 3-weekly intervals) for four cycles followed by docetaxel (100 mg/m(2) at 3-weekly intervals) for four cycles (n=2073) or control (n=2089). For the control regimen, centres chose either FEC for eight cycles (n=1265) or epirubicin (100 mg/m(2) at 3-weekly intervals) for four cycles followed by CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) at 4-weekly intervals) for four cycles (n=824). The primary endpoint was disease-free survival. Analysis was by intention to treat (ITT). This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN79718493.

Findings: All randomised patients were included in the ITT population. With a median follow-up of 62 months, disease-free survival events were seen in 517 of 2073 patients in the experimental group compared with 539 of 2089 controls (hazard ratio [HR] 0.95, 95% CI 0.85-1.08; p=0.44). 75.6% (95% CI 73.7-77.5) of patients in the experimental group and 74.3% (72.3-76.2) of controls were alive and disease-free at 5 years. The proportion of patients who reported any acute grade 3 or 4 adverse event was significantly greater in the experimental group than in the control group (p<0.0001); the most frequent events were neutropenia (937 events vs 797 events), leucopenia (507 vs 362), and lethargy (456 vs 272).

Interpretation: This study did not show any overall gain from the addition of docetaxel to standard anthracycline chemotherapy. Exploration of predictive biomarker-defined subgroups might have the potential to better target the use of taxane-based therapy.

Funding: Cancer Research UK (CRUK 01/001), Sanofi-Aventis, Pfizer, and Roche.

Figures

Figure 1
Figure 1
Trial profile CMF=cyclophosphamide, methotrexate, and fluorouracil. DCIS=ductal carcinoma in situ. E-CMF=epirubicin followed by CMF. FEC=fluorouracil, epirubicin, and cyclophosphamide. FEC-D=FEC followed by docetaxel. Numbers of patients screened and assessed for eligibility were not routinely collected.
Figure 2
Figure 2
Disease-free survival (A) and overall survival (B) by treatment group FEC-D=fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel. HR=hazard ratio. Number in parentheses indicates events occurring after year 5. Disease-free survival events were seen in 517 of 2073 patients in the FEC-D group and in 539 of 2089 patients in the control group.
Figure 3
Figure 3
Sensitivity analysis hazard ratios for disease-free survival for all patients receiving eight cycles of chemotherapy and all patients with relative dose intensity more than 85% FEC-D=fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel. ITT=intention to treat.
Figure 4
Figure 4
Hazard ratios for disease-free survival by centre's choice of control regimen, and patient and tumour characteristics E-CMF=epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil. ER=oestrogen receptor. FEC=fluorouracil, epirubicin, and cyclophosphamide. FEC-D=FEC followed by docetaxel. HER2=human epidermal growth factor receptor 2. HR=hazard ratio. *p=0·55 for heterogeneity.
Figure 5
Figure 5
Hazard ratios for disease-free survival by combined ER and HER2 status in (A) all patients and (B) node-positive patients ER=oestrogen receptor. FEC-D=fluorouracil, epirubicin, and cyclophosphamide followed by docetaxel. HER2=human epidermal growth factor receptor 2. HR=hazard ratio.
Figure 6
Figure 6
Meta-analysis of disease-free survival for trials of taxane-based versus anthracycline-based adjuvant chemotherapy A=doxorubicin. C=cyclophosphamide. D=docetaxel. dd=dose dense. F=fluorouracil. P=paclitaxel. E=epirubicin. M=methotrexate. HR=hazard ratio. *HR from Cochrane review.
Figure 7
Figure 7
Meta-analysis of disease-free survival for trials of taxane-based versus anthracycline-based adjuvant chemotherapy that reported combined ER/HER2 subgroup analyses ER=oestrogen receptor. HER2=human epidermal growth factor receptor 2. p=0·03 heterogeneity test for comparison of the HRs across the four subgroups of ER/HER2 status.

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References

    1. Early Breast Cancer Trialists' Collaborative Group Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet. 1998;352:930–942. - PubMed
    1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365:1687–1717. - PubMed
    1. Henderson IC, Berry DA, Demetri GD. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003;21:976–983. - PubMed
    1. Mamounas EP, Bryant J, Lembersky B. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005;23:3686–3696. - PubMed
    1. Dowsett M, Bartlett J, Ellis IO. Correlation between immunohistochemistry (HercepTest) and fluorescence in situ hybridization (FISH) for HER-2 in 426 breast carcinomas from 37 centres. J Pathol. 2003;199:418–423. - PubMed

Uncited reference

    1. Francis P, Crown J, Di Leo A. Adjuvant chemotherapy with sequential or concurrent anthracycline and docetaxel: Breast International Group 02-98 randomized trial. J Natl Cancer Inst. 2008;100:121–133. - PubMed
    1. Goldstein LJ, O'Neill A, Sparano JA. Concurrent doxorubicin plus docetaxel is not more effective than concurrent doxorubicin plus cyclophosphamide in operable breast cancer with 0 to 3 positive axillary nodes: North American Breast Cancer Intergroup Trial E 2197. J Clin Oncol. 2008;26:4092–4099. - PMC - PubMed
    1. Jones S, Holmes FA, O'Shaughnessy J. Docetaxel with cyclophosphamide is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J Clin Oncol. 2009;27:1177–1183. - PubMed
    1. Martin M, Pienkowski T, Mackey J. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005;352:2302–2313. - PubMed
    1. Martin M, Lluch A, Segui MA. TAC versus FAC as adjuvant chemotherapy for high-risk node-negative breast cancer: results of the GEICAM 9805 trial. Ann Oncol. 2008;19(suppl 8):viii77–viii88. abstract 1830.

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