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Anthracycline and taxane-based chemotherapy versus docetaxel and cyclophosphamide in the adjuvant treatment of HER2-negative breast cancer patients: a systematic review and meta-analysis of randomized controlled trials

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Abstract

Purpose

Standard adjuvant chemotherapy for HER2-negative breast cancer consists generally in an anthracycline and taxane-based regimen (A+T). The TC (docetaxel and cyclophosphamide) regimen arises as a potential alternative, although individual randomized controlled trials (RCTs) could not demonstrate the non-inferiority of TC over A+T. This is a systematic review and meta-analysis of RCTs comparing 6 cycles of TC versus sequential A+T in the adjuvant treatment of HER2-negative breast cancer.

Methods

A systematic literature search was performed to identify RCTs comparing TC versus A+T. Disease-free survival (DFS) and overall survival (OS) were assessed. Subgroup analyses of DFS according to hormone receptor status, lymph node involvement, and menopausal status were performed. Hazard ratios (HRs) and 95% confidence intervals (CI) for DFS and OS were extracted from each trial, and a pooled analysis was conducted using the random-effect model. The Higgins’ I-Squared Test was used to quantify heterogeneity.

Results

Seven RCTs were included (12,741 patients). Overall, no difference was observed between TC and A+T in DFS (HR 1.08, 95% CI 0.96–1.20) and OS (HR 1.05; 95% CI 0.90–1.22). A trend favoring A+T was observed in hormone receptor-negative (HR 1.12, 95% CI 0.93–1.34) and N2 patients (HR 1.25; 95% CI 0.82–1.90). Emesis/vomiting, mucositis, thrombocytopenia and sensory neuropathy were significantly more frequent with A+T.

Conclusion

As adjuvant treatment of HER2-negative breast cancer, sequential A+T regimen was associated with increased risk of toxicities and no clear survival benefit as compared to 6 cycles of TC. Higher-risk patients may benefit the most from A+T, whilst TC may be an efficacious and less toxic alternative for lower-risk patients.

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Acknowledgements

Matteo Lambertini acknowledges the support from the European Society for Medical Oncology (ESMO) for a Translational Research Fellowship at the Institut Jules Bordet (Brussels, Belgium).

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Authors and Affiliations

  1. Department of Medical Oncology, Institut Jules Bordet and Université Libre de Bruxelles (ULB), Boulevard de Waterloo 121, 1000, Brussels, Belgium

    Rafael Caparica, Evandro de Azambuja & Matteo Lambertini

  2. Clinical Epidemiology Unit, Ospedale Policlinico San Martino, Genova, Italy

    Marco Bruzzone & Marcello Ceppi

  3. Department of Medical Oncology, U.O. Oncologia Medica 2, Ospedale Policlinico San Martino, University of Genova, Genova, Italy

    Francesca Poggio

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  1. Rafael Caparica
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Correspondence to Matteo Lambertini.

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Conflict of interest

Evandro de Azambuja received honoraria from Roche-Genentech, research grant from Roche–Genentech (to the insitution) and travel grants from Roche-Genentech and GlaxoSmithKline outside the submitted work. Matteo Lambertini served as a consultant for Teva and received honoraria from Theramex outside the submitted work All the other authors declare no conflicts of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Caparica, R., Bruzzone, M., Poggio, F. et al. Anthracycline and taxane-based chemotherapy versus docetaxel and cyclophosphamide in the adjuvant treatment of HER2-negative breast cancer patients: a systematic review and meta-analysis of randomized controlled trials. Breast Cancer Res Treat 174, 27–37 (2019). https://doi.org/10.1007/s10549-018-5055-9

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