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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

Paul Ellis  1 , Peter Barrett-Lee, Lindsay Johnson, David Cameron, Andrew Wardley, Susan O'Reilly, Mark Verrill, Ian Smith, John Yarnold, Robert Coleman, Helena Earl, Peter Canney, Chris Twelves, Christopher Poole, David Bloomfield, Penelope Hopwood, Stephen Johnston, Mitchell Dowsett, John M S Bartlett, Ian Ellis, Clare Peckitt, Emma Hall, Judith M Bliss; TACT Trial Management Group; TACT Trialists
Collaborators, Affiliations
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. .

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.

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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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Comment in

References

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