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Comparison of Adjuvant Regimens in Early-Stage Breast Cancer

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Key Points

  • On the basis of overall survival benefit and toxicity severity profile, sequential anthracycline-cyclophosphamide and taxane was considered the most effective adjuvant regimen.
  • Docetaxel and cyclophosphamide was associated with a similar survival benefit and toxicity severity profile.

In a systematic review and network meta-analysis reported in JAMA Oncology, Fujii et al found that sequential anthracycline-cyclophosphamide and taxane (AC-T) appears to be the most effective adjuvant regimen in early-stage breast cancer in terms of association with overall survival and toxicity.

Study Details

The analysis included randomized clinical trials of adjuvant therapy that compared at least two of the following regimens: no adjuvant chemotherapy; sequential AC-T; concurrent anthracycline-cyclophosphamide and taxane (ACT); anthracycline-cyclophosphamide without taxane (AC); docetaxel and cyclophosphamide (TC); cyclophosphamide, methotrexate, and fluorouracil (CMF); and platinum-containing regimens. The literature search included MEDLINE, Embase, and Cochrane Library articles published before June 2015, ASCO Annual Meeting abstracts through December 2014, and American Association for Cancer Research Annual Meeting abstracts through December 2014.

Overall Survival

Overall, 24 trials were identified. Compared with sequential AC-T, TC (hazard ratio [HR] = 0.93, 95% confidence interval [CI] = 0.62–1.40), platinum-containing regimens (HR = 0.93, 95% CI = 0.66–1.31), and concurrent ACT (HR = 1.03, 95% CI = 0.90–1.18) had a similar overall survival benefit, whereas overall survival was worse with CMF (HR = 1.56, 95% CI = 1.32–1.85), anthracycline alone (HR = 1.22, 95% CI = 1.10–1.37), and no adjuvant therapy (HR = 1.76, 95% CI = 1.40–2.21).

On meta-regression analysis adjusting for hormone receptor status, there were no significant differences in overall survival for sequential AC-T vs concurrent ACT, anthracycline alone, platinum-containing regimens, or TC, with CMF being associated with significantly poorer survival.

Toxicity

Analysis of toxicity consisted of comparing the frequency of unacceptable adverse events, defined as those of grade ≥ 3 that may require dose reduction or schedule delay. Compared with sequential AC-T, risk appeared to be increased with concurrent ACT (odds ratio [OR] = 1.95, 95% CI = 0.97–3.93) and platinum-containing regimens (OR = 3.55, 95% CI = 0.80–15.71) and similar or reduced with anthracycline alone (OR = 0.73, 95% CI = 0.41–1.32), TC (OR = 0.56, 95% CI = 0.13–2.35), and CMF (OR = 0.18, 95% CI = 0.07–0.48).

The investigators concluded: “Sequential AC-T is likely to be the most effective adjuvant therapy regimen for early-stage breast cancer regardless of hormone receptor status.” They noted: “TC was similar to sequential AC-T in terms of treatment effect and unacceptable [adverse events] and might be considered as a first choice treatment for patients with high risk of cardiotoxic effects.”

Naoto T. Ueno, MD, PhD, of The University of Texas MD Anderson Cancer Center, is the corresponding author of the JAMA Oncology article.

Funding was provided by the Morgan Welch Inflammatory Breast Cancer Research Program, the State of Texas Rare and Aggressive Breast Cancer Research Program, and the National Cancer Institute.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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