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Clinical Study

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



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.


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.


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.


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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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




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).

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