A Randomized Phase II Study of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Operable HER2-negative Breast Cancer

Denise A. Yardley, Dianna Shipley, John Zubkus, Gail L. Wright, Patrick J. Ward, Aruna Mani, Mythili Shastry, Lindsey Finney, Laura DeBusk, John D. Hainsworth

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background: Eribulin mesylate is a non–taxane microtubule inhibitor effective in the treatment of metastatic breast cancer refractory to anthracyclines and taxanes. In preclinical studies, additional mechanisms of eribulin included reversal of epithelial mesenchymal transition and tumor vascular remodeling. The present study compared the safety and efficacy of eribulin plus cyclophosphamide (ErC) to docetaxel plus cyclophosphamide (TC) as neoadjuvant therapy for operable HER2 breast cancer. Patients and Methods: Women with invasive HER2 breast adenocarcinoma with no distant metastases were eligible. After a 10-patient safety lead-in, the patients were randomized 2:1 to receive either ErC (eribulin 1.4 mg/m 2 on days 1 and 8 plus cyclophosphamide 600 mg/m 2 on day 1) or TC (docetaxel 75 mg/m 2 plus cyclophosphamide 600 mg/m 2 on day 1) administered every 21 days for 6 cycles, followed by surgery. The pathologic complete response (pCR) rate was the primary endpoint. Tumor samples collected at baseline and at surgery were assayed for select epithelial mesenchymal transition and vascular density markers: E-cadherin, vimentin, and CD31 expression. Results: A total of 76 patients were enrolled. Of the 76 patients, 10 received ErC in the lead-in phase and 66 were randomized to ErC (n = 44) or TC (n = 22). The pCR rates with ErC and TC were 13% and 9%, respectively. Both regimens produced frequent neutropenia and peripheral neuropathy. Both regimens increased vascular density as measured by CD31 staining. Conclusion: The neoadjuvant regimens of ErC and TC resulted in relatively low pCR rates in this patient population. No unexpected toxicities were observed. Our results also provided no suggestion that ErC is a neoadjuvant treatment with greater efficacy than that of standard regimens.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalClinical breast cancer
Volume19
Issue number1
DOIs
StatePublished - Feb 2019

Keywords

  • ErC
  • HER2
  • NAC
  • TC

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'A Randomized Phase II Study of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Operable HER2-negative Breast Cancer'. Together they form a unique fingerprint.

  • Cite this

    Yardley, D. A., Shipley, D., Zubkus, J., Wright, G. L., Ward, P. J., Mani, A., Shastry, M., Finney, L., DeBusk, L., & Hainsworth, J. D. (2019). A Randomized Phase II Study of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Operable HER2-negative Breast Cancer. Clinical breast cancer, 19(1), 1-9. https://doi.org/10.1016/j.clbc.2018.08.006