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

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/m2 on days 1 and 8 plus cyclophosphamide 600 mg/m2 on day 1) or TC (docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 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. The present phase II study compared the combination of eribulin plus cyclophosphamide (ErC) to docetaxel plus cyclophosphamide (TC) as neoadjuvant therapy for HER2 breast cancer patients. Patients received either eribulin 1.4 mg/m2 on days 1 and 8 plus cyclophosphamide 600 mg/m2 on day 1 or docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 on day 1 for 6 cycles before surgery. Neoadjuvant ErC showed no greater efficacy than TC.

Original languageEnglish (US)
JournalClinical Breast Cancer
DOIs
StateAccepted/In press - Jan 1 2018
Externally publishedYes

Fingerprint

eribulin
docetaxel
Neoadjuvant Therapy
Cyclophosphamide
Breast Neoplasms
Epithelial-Mesenchymal Transition
Blood Vessels

Keywords

  • ErC
  • HER2
  • NAC
  • TC

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A Randomized Phase II Study of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Operable HER2-negative Breast Cancer. / Yardley, Denise A.; Shipley, Dianna; Zubkus, John; Wright, Gail L.; Ward, Patrick J.; Mani, Aruna; Shastry, Mythili; Finney, Lindsey; DeBusk, Laura; Hainsworth, John D.

In: Clinical Breast Cancer, 01.01.2018.

Research output: Contribution to journalArticle

Yardley, Denise A. ; Shipley, Dianna ; Zubkus, John ; Wright, Gail L. ; Ward, Patrick J. ; Mani, Aruna ; Shastry, Mythili ; Finney, Lindsey ; DeBusk, Laura ; Hainsworth, John D. / A Randomized Phase II Study of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Operable HER2-negative Breast Cancer. In: Clinical Breast Cancer. 2018.
@article{a37547e989f8441b96a8d9772eadc8d1,
title = "A Randomized Phase II Study of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Operable HER2-negative Breast Cancer",
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/m2 on days 1 and 8 plus cyclophosphamide 600 mg/m2 on day 1) or TC (docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 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. The present phase II study compared the combination of eribulin plus cyclophosphamide (ErC) to docetaxel plus cyclophosphamide (TC) as neoadjuvant therapy for HER2− breast cancer patients. Patients received either eribulin 1.4 mg/m2 on days 1 and 8 plus cyclophosphamide 600 mg/m2 on day 1 or docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 on day 1 for 6 cycles before surgery. Neoadjuvant ErC showed no greater efficacy than TC.",
keywords = "ErC, HER2, NAC, TC",
author = "Yardley, {Denise A.} and Dianna Shipley and John Zubkus and Wright, {Gail L.} and Ward, {Patrick J.} and Aruna Mani and Mythili Shastry and Lindsey Finney and Laura DeBusk and Hainsworth, {John D.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.clbc.2018.08.006",
language = "English (US)",
journal = "Clinical Breast Cancer",
issn = "1526-8209",
publisher = "Elsevier",

}

TY - JOUR

T1 - A Randomized Phase II Study of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Operable HER2-negative Breast Cancer

AU - Yardley, Denise A.

AU - Shipley, Dianna

AU - Zubkus, John

AU - Wright, Gail L.

AU - Ward, Patrick J.

AU - Mani, Aruna

AU - Shastry, Mythili

AU - Finney, Lindsey

AU - DeBusk, Laura

AU - Hainsworth, John D.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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/m2 on days 1 and 8 plus cyclophosphamide 600 mg/m2 on day 1) or TC (docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 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. The present phase II study compared the combination of eribulin plus cyclophosphamide (ErC) to docetaxel plus cyclophosphamide (TC) as neoadjuvant therapy for HER2− breast cancer patients. Patients received either eribulin 1.4 mg/m2 on days 1 and 8 plus cyclophosphamide 600 mg/m2 on day 1 or docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 on day 1 for 6 cycles before surgery. Neoadjuvant ErC showed no greater efficacy than TC.

AB - 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/m2 on days 1 and 8 plus cyclophosphamide 600 mg/m2 on day 1) or TC (docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 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. The present phase II study compared the combination of eribulin plus cyclophosphamide (ErC) to docetaxel plus cyclophosphamide (TC) as neoadjuvant therapy for HER2− breast cancer patients. Patients received either eribulin 1.4 mg/m2 on days 1 and 8 plus cyclophosphamide 600 mg/m2 on day 1 or docetaxel 75 mg/m2 plus cyclophosphamide 600 mg/m2 on day 1 for 6 cycles before surgery. Neoadjuvant ErC showed no greater efficacy than TC.

KW - ErC

KW - HER2

KW - NAC

KW - TC

UR - http://www.scopus.com/inward/record.url?scp=85053752919&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053752919&partnerID=8YFLogxK

U2 - 10.1016/j.clbc.2018.08.006

DO - 10.1016/j.clbc.2018.08.006

M3 - Article

JO - Clinical Breast Cancer

JF - Clinical Breast Cancer

SN - 1526-8209

ER -