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Efficacy and safety of nab-paclitaxel 125 mg/m2 and nab-paclitaxel 150 mg/m2 compared to paclitaxel in early high-risk breast cancer. Results from the neoadjuvant randomized GeparSepto study (GBG 69)

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Abstract

Purpose

The GeparSepto study demonstrated that the use of nab-paclitaxel instead of paclitaxel prior to anthracycline-based chemotherapy could lead to a significantly increased pCR rate, especially in the triple negative subpopulation. We report efficacy and safety for patients treated with two different doses of nab-paclitaxel in comparison to weekly solvent-formulated paclitaxel.

Methods

Patients were treated for 12 weeks with either intravenous nab-paclitaxel 150 mg/m2 (nP150) weekly, after study amendment 125 mg/m2 (nP125) weekly or solvent-based paclitaxel 80 mg/m2 (P80) weekly followed by epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 on day 1 for four 3-week cycles.

Results

229 patients received nP150, 377 nP125. Baseline characteristics were fairly balanced between these two sequential cohorts as well as compared to 601 patients receiving P80 except for hormone receptor status, HER2 status, and Ki67. Taxane treatment was discontinued in 26.8% (nP150), 16.6% (nP125), and 13.3% of (P80) patients, respectively. Median relative total dose intensity (mRTDI) based on 125 mg/m2 for nP was 103% with nP150, 95% with nP125, 99% with P80 before and 98% with P80 after the amendment. PSN grade 3–4 was observed in 14.5% of patients with nP150, 8.1% of patients with nP125 (p = 0.018), and 2.7% of patients with P80. Overall pCR before the amendment was 33.6% after nP150 and 23.5% after P80 (OR 1.65 [95% CI 1.10–2.50]; p = 0.022); pCR after the amendment was 41.4% after nP125, and 32.4% after P80 (1.48 [95% CI 1.10–1.99]; p = 0.013).

Conclusions

Nab-paclitaxel 125 mg/m2 was associated with a better safety profile and compliance without compromising the efficacy compared to nab-paclitaxel 150 mg/m2.

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Acknowledgements

We would like to thank all investigators and patients that participated in the GeparSepto study.

Funding

The trial was sponsored by GBG Forschungs GmbH with financial support from Celgene and Roche.

Author information

Authors and Affiliations

  1. German Breast Group, GBG Forschungs GmbH, Martin Behaim Strasse 12, 63263, Neu-Isenburg, Germany

    Jenny Furlanetto, Valentina Nekljudova, Sibylle Loibl & Gunter von Minckwitz

  2. Sana Klinikum Offenbach, Offenbach, Germany

    Christian Jackisch

  3. Helios Klinikum Berlin-Buch, Berlin, Germany

    Michael Untch

  4. National Center for Tumor Disease, University Hospital Heidelberg, Heidelberg, Germany

    Andreas Schneeweiss

  5. Elisabeth Krankenhaus Kassel, Kassel, Germany

    Sabine Schmatloch

  6. University Women’s Hospital Essen, Essen, Germany

    Bahriye Aktas

  7. Institute of Pathology and German Cancer Consortium (DKTK), Charité-University Hospital, Berlin, Germany

    Carsten Denkert

  8. St. Barbara Klinik Heessen, Hamm, Germany

    Hermann Wiebringhaus

  9. Interdisziplinäres Brustzentrum an den Kliniken Essen-Mitte, Essen, Germany

    Sherko Kümmel

  10. Brustzentrum in Krankenhaus Köln-Holweide, Cologne, Germany

    Mathias Warm

  11. Klinikum rechts der Isar der TU München, Klinik und Poliklinik für Frauenheilkunde, Munich, Germany

    Stefan Paepke

  12. Onkologische Schwerpunktpraxis, Bielefeld, Germany

    Marianne Just

  13. Klinikum zum Roten Kreuz München, Munich, Germany

    Claus Hanusch

  14. Marien Hospital Witten, Witten, Germany

    John Hackmann

  15. Frauenklinik an der Charité-University Hospital, Berlin, Germany

    Jens Uwe Blohmer

  16. Klinik Mutterhaus der Borromäerinnen, Trier, Germany

    Michael Clemens

  17. Universitäts-Frauenklinik, Magdeburg, Germany

    Serban Dan Costa

  18. Universitäts-Frauenklinik, Rostock, Germany

    Bernd Gerber

Authors
  1. Jenny Furlanetto
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  2. Christian Jackisch
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  3. Michael Untch
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  4. Andreas Schneeweiss
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  11. Stefan Paepke
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  12. Marianne Just
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  16. Michael Clemens
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  18. Bernd Gerber
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  19. Valentina Nekljudova
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  20. Sibylle Loibl
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  21. Gunter von Minckwitz
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Corresponding author

Correspondence to Jenny Furlanetto.

Ethics declarations

Conflict of interest

Denkert C: Shareholder and cofounder of Sividon Diasgnostics Cologne, Hanusch C: Honoraria by Celgene and Roche, Jakisch C: Honoraria by Celgene, Loibl S: Institution received research grants by Celgene and Roche, von Minckwitz G: Institution received research grants by Celgene and Roche. All other authors have declared no conflicts 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.

Informed consent

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

Additional information

The original GeparSepto trial is registered with ClinicalTrials.gov number NCT01583426. Results have been published in Lancet Oncology 17:345–56, 2016.

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Furlanetto, J., Jackisch, C., Untch, M. et al. Efficacy and safety of nab-paclitaxel 125 mg/m2 and nab-paclitaxel 150 mg/m2 compared to paclitaxel in early high-risk breast cancer. Results from the neoadjuvant randomized GeparSepto study (GBG 69). Breast Cancer Res Treat 163, 495–506 (2017). https://doi.org/10.1007/s10549-017-4200-1

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  • DOI: https://doi.org/10.1007/s10549-017-4200-1

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