Sequential docetaxel as adjuvant chemotherapy for early breast cancer (TACT): an open-label, phase III, randomised controlled trial

Abstract

SummaryBackgroundIncorporation 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.MethodsIn 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/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2 at 3-weekly intervals) for four cycles followed by docetaxel (100 mg/m2 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/m2 at 3-weekly intervals) for four cycles followed by CMF (cyclophosphamide 600 mg/m2, methotrexate 40 mg/m2, and fluorouracil 600 mg/m2 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.FindingsAll 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).InterpretationThis 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.FundingCancer Research UK (CRUK 01/001), Sanofi-Aventis, Pfizer, and Roche.

In the Era of Genomics, Should Tumor Size Be Reconsidered as a Criterion for Neoadjuvant Chemotherapy?

“…However, it is also important to consider the risk and toxicity of neoadjuvant chemotherapy for patients: a substantial proportion of patients (20%) experienced serious adverse events in the present study. The toxicity profile and incidence of grade 3 alopecia, nausea, neuropathy, febrile neutropenia, and asthenia is consistent with large prospective randomized trials in which patients are treated with anthracycline-and taxane-containing regimens [19,20]. This study is the first prospectively designed analysis of patients with ER-positive, HER2-negative tumors who received neoadjuvant chemotherapy that includes the assessment of the RS by Oncotype DX assay.…”

The cell cycle and cancer

“…The disappointing intent-to-treat analyses of large, conventionally designed trials, such as TACT and tAnGo, suggests that further improvements in adjuvant treatment will require individualized therapeutic decisions [116,117]. Cell cycle phase analysis of breast and ovarian cancers has shown that it is tumours displaying the accelerated cell cycle phenotype that are most likely to show a clinically relevant response to S-or M-phase-directed agents (Table 1, Figure 3B) [3,74,110,111,118].…”

Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer

“…Later, anthracycline combinations were found to be slightly but significantly more effective than the CMF regimen [2]. More recently, several adjuvant phase III trials have shown that taxane regimens further reduce the likelihood of recurrence and death, compared to anthracycline-containing combinations [3][4][5][6][7][8][9][10], but the absolute benefit was again small, and some trials were unable to show any advantage for the taxane arm [11,12]. Taxanes and anthracyclines can induce some acute and chronic toxicities of considerable clinical concern.…”