Meta-Analysis Confirms Adjuvant Sequential AC-T Best for Early Breast Cancer

US researchers find sequential anthracycline–cyclophosphamide and taxane has the best balance of efficacy and toxicity in early-stage breast cancer patients

medwireNews: Sequential anthracycline–cyclophosphamide and taxane (AC-T) should remain the “first choice” among adjuvant chemotherapy options for patients with early-stage breast cancer on the basis of efficacy and risk of adverse events (AEs), recommend researchers who conducted a network meta-analysis.

But based on the analysis of adverse events, they add that the combination of docetaxel and cyclophosphamide could be “useful for patients with a high risk of cardiotoxicity”.

Using data from 21 randomised controlled trials comparing two or more adjuvant treatment options in this patient population, the team found no significant differences in overall survival (OS) between patients treated with sequential AC-T and those given concurrent ACT, platinum-containing regimens or docetaxel and cyclophosphamide.

Event-free survival (EFS), assessed using data from 22 trials, was also comparable between the sequential AC-T group and the concurrent ACT, platinum-containing or docetaxel and cyclophosphamide groups.

But compared with patients receiving sequential AC-T, those given anthracycline–cyclophosphamide without taxane, cyclophosphamide, methotrexate and fluorouracil (CMF), or no adjuvant therapy had significantly worse OS, with hazard ratios (HRs) of 1.22, 1.56 and 1.76, respectively. EFS was also significantly poorer, with corresponding HRs of 1.26, 1.47 and 1.78.

The results of a meta-regression analysis to adjust for the effect of hormone receptor status on OS and EFS were similar to those of the overall analysis, report the study authors in JAMA Oncology.

They also used data from 17 trials to compare the treatment regimens with respect to the occurrence of unacceptable adverse events, defined as those of grade 3 or higher. Compared with sequential AC-T, platinum-containing regimens tended to be associated with more overall (HR=3.55) and significantly more nonhaematological unacceptable AEs (HR=5.17), while CMF caused significantly fewer overall (HR=0.18), haematological (HR=0.29) and nonhaematological (HR=0.32) unacceptable AEs.

There was no significant difference between sequential AC-T and docetaxel and cyclophosphamide in terms of overall, haematological and nonhaematological unacceptable AEs.

Researcher Naoto Ueno, from the University of Texas MD Anderson Cancer Center in Houston, USA, and fellow investigators recommend that sequential AC-T remain the “first choice” in the general population, but highlight the potential of docetaxel and cyclophosphamide in patients with a high risk of cardiotoxic effects.

They also recommend against prescribing platinum-containing regimens for the general population of breast cancer patients as “they are not superior to sequential AC-T in terms of OS and tend to be more toxic.”

The team adds: “Further clinical studies may be required to investigate target markers that will predict patients with a higher likelihood of response to platinum-containing regimens.”


Fujii T, Le Du F, Xiao L, et al. Effectiveness of an Adjuvant Chemotherapy Regimen for Early-Stage Breast Cancer. A Systematic Review and Network Meta-analysis. JAMA Oncol 2015; Advance online publication 24 September. doi:10.1001/jamaoncol.2015.3062

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