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Updated efficacy of adjuvant epirubicin plus cyclophosphamide followed by taxanes versus carboplatin plus taxanes in early triple-negative breast cancer in phase 2 trial: 8.1-year median follow-up

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Abstract

Background

Paclitaxel/docetaxel after doxorubicin plus cyclophosphamide (ECT) is considered as an adjuvant chemotherapy and improves the survival of early triple-negative breast cancer (TNBC) patients. We aim to assess whether carboplatin plus taxanes (TP) is non-inferior to ECT in prolonging the survival time.

Methods

TNBC patients were randomized (1:1) to receive ECT (90 mg/m2 epirubicin + 600 mg/m2 cyclophosphamide followed by 75 mg/m2 docetaxel or 175 mg/m2 paclitaxel every 3 weeks, n = 154) or TP (75 mg/m2 docetaxel or 175 mg/m2 paclitaxel + carboplatin AUC 5 every 3 weeks, n = 154). These expression of SPARC, PD-L1, and BRCA were studied. Patients were followed up for disease-free survival (DFS), overall survival (OS), and safety.

Results

We recruited 308 TNBC patients (median follow-up of 97.6 months). The median DFS and OS were not reached; the 8-year DFS rate of ECT and TP arms was 78.4% and 81.7%, respectively, while the 8-year OS rate were 87.2% and 89.1%, respectively. In the SPARC (> 50%) subgroup analysis, the TP arm had longer DFS (P = 0.049) and a tendency with better OS (P = 0.06) than ECT arm. No significant differences were observed in the DFS and OS between the ECT arm and TP arm in TNBC with SPARC (≤ 50%), PD-L1 (−) PD-L1 (+), and BRCA mutation or BRCA wild (all P values > 0.05).

Conclusion

TP showed non-inferiority for DFS and OS compared with ECT in early TNBC. TP may be an effective alternative chemotherapy for TNBC patients whom the standard ECT regimen is not being used.

Trail Registration

ClinicalTrials.gov identifier NCT01150513

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Data availability

The datasets analyzed during the present study are not publicly available due to its scope but are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank all patients and their families, the study investigators and their staff, and the ethics committees of the participating hospitals.

Funding

This work was supported by the National Key R&D Program of China (2018YFC0115204), CSCO Pilot Oncology Research Fund (Y-2019AZMS-0377), Capital Health Development Research Project (2018-2-4023), and Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences Clinical and Translational Medicine Research Fund (12019XK320071).

Author information

Author notes

  1. Fangchao Zheng and Feng Du have contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Oncology, National Cancer Centre/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Beijing, 100021, China

    Fangchao Zheng, Jiayu Wang, Zixuan Yang, Ruigang Cai, Fei Ma, Ying Fan, Qing Li, Pin Zhang, Binghe Xu & Peng Yuan

  2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), The VIPII Gastrointestinal Cancer Division of Medical Department, Peking University Cancer Hospital and Institute, Beijing, 100021, China

    Feng Du

  3. Department of Pathology, Cancer Hospital/Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Wenmiao Wang

  4. Shandong Cancer Hospital/Institute, Jinan, 250117, Shandong, China

    Yongsheng Wang

  5. Beijing Luhe Hospital, Capital Medical University, Beijing, 101100, China

    Ming Li

  6. Breast Disease Diagnosis and Treatment Center, Affiliated Hospital of Qinghai University and Affiliated Cancer Hospital of Qinghai University, Xining, 810000, China

    Jiuda Zhao

  7. Department of VIP Medical Services, National Cancer Centre/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China

    Xue Wang, Jian Yue & Peng Yuan

Authors
  1. Fangchao Zheng
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Contributions

Conception and design: PY, FZ, and FD. Acquisition and analysis of data: FZ, FD, and PY. Provided the clinical data: BX, PY, WW, YW, ML, JW, RC, FM, YF, QL, and PZ. Writing, review, and/or revision of the manuscript: FZ, FD, YW, JZ, ZY, XW, JY, JW, and PY. Study supervision: PY and BX.

Corresponding authors

Correspondence to Binghe Xu or Peng Yuan.

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Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

The study was carried out in accordance with the Declaration of Helsinki.

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Good Clinical Practice Guidelines and was also approved by the ethics committees of the participating hospitals.

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Not applicable.

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Supplementary Information

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10549_2021_6401_MOESM1_ESM.pdf

Supplementary file1 (PDF 509 KB) The restricted mean survival time (RMST) of ECT arm and TP arm in 60 months (a), 96 months (b), and 120 months (c). TP, taxanes plus carboplatin; ECT, epirubicin and cyclophosphamide followed by docetaxel or paclitaxel.

10549_2021_6401_MOESM2_ESM.pdf

Supplementary file2 (PDF 25 KB) Kaplan–Meier plots showing the (a) DFS and (b) OS rates of PD-L1 (+) TNBC patients. Kaplan–Meier plots showing (c) DFS and (d) OS rates of PD-L1(-) TNBC patients. TNBC, triple-negative breast cancer; PD-L1, programmed cell death ligand 1; DFS, disease-free survival; OS, overall survival.

10549_2021_6401_MOESM3_ESM.pdf

Supplementary file3 (PDF 166 KB) Kaplan–Meier plots showing the (a) DFS and (b) OS rates of TNBC patients with BRCA mutation or BRCA wild. DFS, disease-free survival; OS, overall survival.

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Zheng, F., Du, F., Wang, W. et al. Updated efficacy of adjuvant epirubicin plus cyclophosphamide followed by taxanes versus carboplatin plus taxanes in early triple-negative breast cancer in phase 2 trial: 8.1-year median follow-up. Breast Cancer Res Treat 191, 97–105 (2022). https://doi.org/10.1007/s10549-021-06401-6

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