Phase II neoadjuvant clinical trial of carboplatin and eribulin in women with triple negative early-stage breast cancer (NCT01372579)

Virginia G. Kaklamani*, Jacqueline S. Jeruss, Elisha Hughes, Kalliopi Siziopikou, Kirsten M. Timms, Alexander Gutin, Victor Abkevich, Zaina Sangale, Cara Solimeno, Krystal L. Brown, Joshua Jones, Anne Renee Hartman, Caitlin Meservey, Borko Jovanovic, Irene Helenowski, Seema A. Khan, Kevin Bethke, Nora Hansen, Regina Uthe, Sara GiordanoSteven Rosen, Kent Hoskins, Jamie Von Roenn, Sarika Jain, Vamsi Parini, William Gradishar

*Corresponding author for this work

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The purpose of this study is to evaluate the efficacy and safety of neoadjuvant treatment with carboplatin and eribulin in patients with early-stage triple negative breast cancer (TNBC), and to explore biomarkers based on DNA and protein expression profiles as predictors of response. Patients with histologically confirmed early-stage TNBC received carboplatin AUC 6 iv every 21 days, and eribulin 1.4 mg/m2 day 1 and day 8 every 21 days for four cycles. The primary endpoint of the study was pathologic complete response (pCR), with secondary endpoints including clinical response and safety of the combination. Exploratory studies assessed DNA-based biomarkers [homologous recombination deficiency (HRD) score, and HR deficiency status (HRD score + BRCA1/BRCA2 mutation status)], protein-based biomarkers (Ki67, TP53, androgen receptor, Cyclin E, CDK2, Cyclin D, CDK4, Pin1 and Smad3), and clinical pretreatment factors as predictors of pCR. 13/30 (43.3 %) patients enrolled in the study achieved pCR. 24 (80.0 %) had a clinical complete or partial response. The combination was safe with mostly grade 1 and 2 toxicities. HRD score (P = 0.0024) and HR deficiency status (P = 0.0012) significantly predicted pCR. Pretreatment cytoplasmic CDK2 was also associated with pCR (P = 0.021). Significant differences in pre- versus post-treatment expression levels of nuclear Cyclin D (P = 0.020), nuclear CDK4 (P = 0.0030), and nuclear Smad3 (P = 0.015) were detected. The combination of carboplatin and eribulin is safe and efficacious in the treatment of early-stage TNBC. HRD score, HR deficiency status, and cytoplasmic CDK2 predicted pCR in this patient population.

Original languageEnglish (US)
Pages (from-to)629-638
Number of pages10
JournalBreast Cancer Research and Treatment
Volume151
Issue number3
DOIs
StatePublished - Jun 4 2015

Keywords

  • BRCA1
  • BRCA2
  • Biomarker studies
  • Breast cancer
  • Homologous recombination deficiency
  • Phase II Trials

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kaklamani, V. G., Jeruss, J. S., Hughes, E., Siziopikou, K., Timms, K. M., Gutin, A., Abkevich, V., Sangale, Z., Solimeno, C., Brown, K. L., Jones, J., Hartman, A. R., Meservey, C., Jovanovic, B., Helenowski, I., Khan, S. A., Bethke, K., Hansen, N., Uthe, R., ... Gradishar, W. (2015). Phase II neoadjuvant clinical trial of carboplatin and eribulin in women with triple negative early-stage breast cancer (NCT01372579). Breast Cancer Research and Treatment, 151(3), 629-638. https://doi.org/10.1007/s10549-015-3435-y