High absolute lymphocyte counts are associated with longer overall survival in patients with metastatic breast cancer treated with eribulin-but not with treatment of physician's choice-in the EMBRACE study

Breast Cancer. 2020 Jul;27(4):706-715. doi: 10.1007/s12282-020-01067-2. Epub 2020 Mar 5.

Abstract

Background: Eribulin, a nontaxane synthetic inhibitor of microtubule dynamics, is widely used to manage locally advanced or metastatic breast cancer (MBC). Eribulin has demonstrated immunomodulatory activity on the tumour microenvironment. Baseline neutrophil-to-lymphocyte ratio (NLR), a marker of immune status, may predict progression-free survival in eribulin treatment. This post hoc analysis assessed predictors for overall survival (OS).

Methods: The phase 3 open-label study (EMBRACE) of eribulin versus treatment of physician's choice (TPC) in patients with MBC provided source data. Baseline absolute lymphocyte counts (ALCs) and NLR were evaluable in 751 and 713 patients, respectively.

Results: Eribulin prolonged OS versus TPC in patients with baseline ALC ≥ 1500/µl (hazard ratio [HR] 0.586; 95% confidence interval [CI] 0.437-0.784; P < 0.001). There was no significant difference by treatment for ALC < 1500/µl (HR 1.002; 95% CI 0.800-1.253; P = 0.989). Univariate and multivariate analyses were performed and identified baseline ALC as a potential predictor of OS in eribulin-treated patients. Interaction analysis of OS supported 1500/µl as a potentially differential cutoff value. NLR at a cutoff value of 3 was associated with prolonged OS (eribulin group). However, similar results were also observed in the TPC group, without apparent interaction effect, suggesting that NLR may be a general prognostic marker rather than a specific predictor of OS for eribulin.

Discussion: This hypothesis-generating study speculates that baseline ALC may be an independent predictor for longer OS in eribulin-treated MBC patients and could be clinically impactful because it can be evaluated without the need for additional invasive procedures.

Trial registration: www.ClinicalTrials.gov code: NCT00388726.

Keywords: Absolute lymphocyte count; Eribulin; Metastatic breast cancer; Overall survival; Treatment of physician’s choice.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / mortality
  • Drug Administration Schedule
  • Female
  • Furans / administration & dosage*
  • Humans
  • Infusions, Intravenous
  • Kaplan-Meier Estimate
  • Ketones / administration & dosage*
  • Lymphocyte Count
  • Lymphocytes / immunology*
  • Middle Aged
  • Neutrophils / immunology
  • Prognosis
  • Progression-Free Survival
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents
  • Furans
  • Ketones
  • eribulin

Associated data

  • ClinicalTrials.gov/NCT00388726