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Weekly carboplatin plus neoadjuvant anthracycline-taxane-based regimen in early triple-negative breast cancer: a prospective phase II trial by the Breast Cancer Task Force of the Belgian Society of Medical Oncology (BSMO)

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Abstract

Aim

To evaluate the pCR rate and toxicity of the addition of weekly carboplatin (Cp) to paclitaxel (wP) and dose-dense (dd) epirubicin/cyclophosphamide (EC) in an open-label phase II study in TNBC patients.

Methods

Patients were included if they had stage II and III TNBC and received wP (80 mg/m2/week) concurrent with weekly Cp (AUC = 2) for 12 weeks, followed by bi-weekly epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) plus granulocyte colony-stimulating factor (G-CSF) for four cycles, followed by surgery. The primary endpoint was the rate of pCR [(ypT0/isypN0)]. Secondary endpoints included safety and drug delivery.

Results

Sixty-three eligible patients were included. Median age was 51 years (range 29–74); 88.9% had stage II disease, 46% were clinically node positive, and 77.8% had grade 3 tumors. Fifty-four percent achieved a pCR. Twelve percent missed two or more doses of wP, whereas at least two cycles of EC were missed in 9.5%. The rate of tolerance without delays or dose reductions is very low (16%). Sixty-two percent had G3/4 neutropenia. Febrile neutropenia occurred in 18 patients of which more than eighty percent occurred during EC despite primary prophylaxis with G-CSF. Thrombocytopenia grade 3/4 was noticed in 11 pts. Three patients developed grade 3 peripheral neuropathy.

Conclusion

The addition of weekly carboplatin to neoadjuvant paclitaxel and dd EC leads to a pCR rate comparable to prior studies (54%). However, hematological toxicity and febrile neutropenia rate was unexpectedly high. Future investigations could focus on reversing the sequence, which may lead to better hematological tolerability.

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Acknowledgements

We want to acknowledge all the co-investigators of the BSMO, the pathology departments, data nurses of the participant sites, and the patients.

Funding

The study was financially supported by Amgen and Teva.

Author information

Authors and Affiliations

  1. Medical Oncology Department, Oncologisch Centrum, UZ Brussel, Brussels, Belgium

    Christel Fontaine, Lore Decoster, Leen Vanacker & Jacques De Greve

  2. Medical Oncology Department, AZ Sint-Lucas, Ghent, Belgium

    Vincent Renard

  3. Medical Oncology Department, Imelda ziekenhuis, Bonheiden, Belgium

    Heidi Van den Bulk

  4. Medical Oncology Department, CHU UCL Namur, Namur, Belgium

    Peter Vuylsteke

  5. Medical Oncology Department, Cliniques Sud-Luxembourg, Virton, Belgium

    Philip Glorieux

  6. Medical Oncology Department, Chwapi, Tournai, Belgium

    Catherine Dopchie

  7. Medical Oncology Department, Institut Jules Bordet, L’Université Libre de Bruxelles (U.L.B), Brussels, Belgium

    Evandro de Azambuja & Ahmad Awada

  8. Department of General Medical Oncology and Department of Oncology, University Hospitals Leuven, Louvain, Belgium

    Hans Wildiers

Authors
  1. Christel Fontaine
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  2. Vincent Renard
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  3. Heidi Van den Bulk
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  5. Philip Glorieux
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  6. Catherine Dopchie
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  7. Lore Decoster
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  9. Evandro de Azambuja
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  10. Jacques De Greve
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  11. Ahmad Awada
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  12. Hans Wildiers
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Corresponding author

Correspondence to Christel Fontaine.

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Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Fontaine, C., Renard, V., Van den Bulk, H. et al. Weekly carboplatin plus neoadjuvant anthracycline-taxane-based regimen in early triple-negative breast cancer: a prospective phase II trial by the Breast Cancer Task Force of the Belgian Society of Medical Oncology (BSMO). Breast Cancer Res Treat 176, 607–615 (2019). https://doi.org/10.1007/s10549-019-05259-z

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  • DOI: https://doi.org/10.1007/s10549-019-05259-z

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