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Clinical Study

Conventional versus reverse sequence of neoadjuvant epirubicin/cyclophosphamide and docetaxel: sequencing results from ABCSG-34

British Journal of Cancer volume 124, pages 1795–1802 (2021)Cite this article

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Abstract

Background

Preoperative chemotherapy containing anthracyclines and taxanes is well established in early-stage breast cancer. Previous studies have suggested that the chemotherapy sequence may matter but definitive evidence is missing. ABCSG trial 34 evaluated the activity of the MUC1 vaccine tecemotide when added to neoadjuvant treatment; the study provided the opportunity for the second randomisation to compare two different anthracycline/taxane sequences.

Methods

HER2-negative early-stage breast cancer patients were recruited to this randomised multicentre Phase 2 study. Patients in the chemotherapy cohort (n = 311) were additionally randomised to a conventional or reversed sequence of epirubicin/cyclophosphamide and docetaxel. Residual cancer burden (RCB) with/without tecemotide was defined as primary study endpoint; RCB in the two chemotherapy groups was a key secondary endpoint.

Results

No significant differences in terms of RCB 0/I (40.1% vs. 37.2%; P = 0.61) or pathologic complete response (pCR) rates (24.3% vs. 25%, P = 0.89) were observed between conventional or reverse chemotherapy sequence. No new safety signals were reported, and upfront docetaxel did not result in decreased rates of treatment delay or discontinuation.

Conclusion

Upfront docetaxel did not improve chemotherapy activity or tolerability; these results suggest that upfront neoadjuvant treatment with anthracyclines remains a valid option.

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Fig. 1: Consort diagram: ABCSG-34 trial overview.
Fig. 2: RCB 0/1 rate and pCR rate in patients with conventional and reverse chemotherapy sequence.
Fig. 3: RCB 0/1 rate and pCR rate in patients with conventional and reverse chemotherapy sequence with or without L-BLP25.

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Acknowledgements

The authors would like to thank Dr. Martina Putz for her support in preparing the final version of this paper.

Author information

Authors and Affiliations

  1. Department of Medicine 1, Clinical Division of Oncology, Medical University of Vienna, Vienna, Austria

    Rupert Bartsch

  2. Department of Gynecology, Medical University of Vienna, Vienna, Austria

    Christian F. Singer, Georg Pfeiler & Tea Maria Muy-Kheng

  3. Breast Center Schwaz, BKH Schwaz, Schwaz, Austria

    Michael Hubalek

  4. Division of Oncology, Department of Internal Medicine and Comprehensive Cancer Center, Medical University of Graz, Graz, Austria

    Herbert Stoeger & Marija Balic

  5. Department of Hemato-Oncology, LKH Hochsteiermark-Leoben, Leoben, Austria

    Angelika Pichler & Christoph Tinchon

  6. Department of Gynecology and Obstetrics, Medical University of Graz, Graz, Austria

    Edgar Petru & Vesna Bjelic-Radisic

  7. Breast Unit, Helios University Hospital Wuppertal, Wuppertal Germany, University Witten/Herdecke, Wuppertal, Germany

    Vesna Bjelic-Radisic

  8. Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectious Disease, Rheumatology, Oncologic Center, Laboratory for Immunological and Molecular Cancer Research, Paracelsus Medical University, Salzburg, Austria

    Richard Greil

  9. Department of Pathology, Medical University of Vienna, Vienna, Austria

    Margaretha Rudas & Zsuzsanna Bago-Horvath

  10. Breastcenter Carinthia, St. Veit, Austria

    Viktor Wette

  11. Internal Medicine I, Hematology with Stem Cell Transplantation, Hemostaseology and Medical Oncology, Ordensklinikum Linz Barmherzige Schwestern, Elisabethinen, Linz, Austria

    Andreas L. Petzer

  12. Karl Landsteiner Institute for Gynecologic Oncology and Senology, Vienna, Austria

    Paul Sevelda

  13. Department of Obstetrics and Gynecology, Medical University of Innsbruck, Innsbruck, Austria

    Daniel Egle

  14. Department of Surgery and Breast Health Center of the Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

    Peter C. Dubsky, Florian Fitzal, Ruth Exner & Raimund Jakesz

  15. Breastcenter St. Anna, Lucerne, Switzerland

    Peter C. Dubsky

  16. Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria

    Martin Filipits

  17. Statistics Department, Austrian Breast & Colorectal Cancer Study Group (ABCSG), Vienna, Austria

    Sophie Frantal

  18. Comprehensive Cancer Center, Medical University Vienna, Vienna, Austria

    Michael Gnant

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Consortia

for the Austrian Breast and Colorectal Cancer Study Group

Contributions

Conception and design: C.S., R.B., P.D., F.F., M.G. and M.H. Development of methodology: V.B.R., P.D., M.F., S.F., M.G., R.G., Z.B.H. and M.R. Acquisition of the data: all authors. Interpretation of the data: all authors. Paper writing: all authors. Paper approval: all authors.

Corresponding author

Correspondence to Marija Balic.

Ethics declarations

Ethics approval and consent to participate

The study was conducted according to the principles of the Declaration of Helsinki and the ICH Guidelines for Good Clinical Practice. The protocol was conducted under EU directive 2001/20/EC and approved by the Ethics Committee of the Medical University of Vienna, Borschkegasse 8b/6, A-1090 Vienna, Austria, as the leading ethics committee. All subjects provided their written informed consent to participate in the study.

Consent to publish

Not applicable.

Data availability

As the regulatory sponsor of this trial, ABCSG has data sovereignty and individual participant data (including de-identified participant data, participant data with identifiers, data dictionary or other specified datasets) will not be shared.

Competing interests

R.B. reports advisory roles at AstraZeneca, Celgene, Daiichi, Eisai, Eli-Lilly, MSD, Novartis, Pfizer, Pierre-Fabre, Puma, Roche, Samsung, lecture honoraria: Accord, AstraZeneca, BMS, Celgene, Eli-Lilly, Novartis, Pfizer, Pierre-Fabre, Roche, Sandoz and received research support from Daiichi, Novartis and Roche, all outside of the submitted work. M.H. reports honoraria and/or travel support from Amgen, AstraZeneca, Celgene, Eli-Lilly, Pfizer, Novartis, Roche all outside the submitted work. A.L.P. reports honoraria and/or travel support from Abbvie, Amgen, AstraZeneca, Bayer, Celgene, Gilead, Janssen, Eli-Lilly, MSD, Pfizer, Novartis, Roche, Sanofi and Takeda all outside the submitted work. D.E. reports honoraria/travel support from Amgen, AstraZeneca, Celgene, Eli-Lilly, MSD, Novartis, Pfizer, Roche and Myriad all outside of the submitted work. M.F. has received honoraria for advisory boards from AstraZeneca, Bayer, Biomedica, Boehringer Ingelheim, Eli-Lilly, Merck Sharp & Dohme, Myriad Genetics Inc., Pfizer and Roche. M.G. reports personal fees/travel support from Amgen, AstraZeneca, Celgene, Eli-Lilly, Invectys, Pfizer, Novartis, Puma, Nanostring, Roche, Medison, LifeBrain, all outside the submitted work; an immediate family member is employed by Sandoz. Z.B.-H. has advisory roles at Biomedica, Roche and Novartis, received lecture honoraria and travel support from Roche and research support from Boehringer Ingelheim. C.F.S., G.P., H.S., A.P., E.P., V.B.-R., R.G., M.R., M.K.T., V.W., P.S., P.D., F.F., R.E., R.J., M.B., C.T. and S.F. declare no competing interests.

Funding information

This study was supported by Merck KGaA, Darmstadt, Germany. The academic non-profit organisation ABCSG was the regulatory sponsor of this trial. Merck provided financial funding and tecemotide. The study was designed and conducted by ABCSG. Merck was not involved in the collection, management, analysis and interpretation of the data. ABCSG prepared and approved the paper and decided to submit the paper for the publication.

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Bartsch, R., Singer, C.F., Pfeiler, G. et al. Conventional versus reverse sequence of neoadjuvant epirubicin/cyclophosphamide and docetaxel: sequencing results from ABCSG-34. Br J Cancer 124, 1795–1802 (2021). https://doi.org/10.1038/s41416-021-01284-2

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