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

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.Clini calTr ials.gov code: NCT00388726

Clinical importance of the absolute count of neutrophils, lymphocytes, monocytes, and platelets in newly diagnosed hepatocellular carcinoma

“…Recent studies have highlighted the crucial role of tumor microenvironment in the tumor progression and treatment response 5 . Furthermore, reports suggest subcategorization of white blood cells or platelets and their functions associated with tumor progression or suppression 6 – 8 . Numerous studies have confirmed the clinical significance of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in HCC 9 – 12 .…”

“…Furthermore, the prognostic significance and/or actual role of each blood cell in various tumors and/or the clinical significance of the absolute blood cell count itself have been investigated 6 – 8 , 14 . The analysis from these studies considered absolute blood cell counts rather than the ratio of these cells to understand the mechanism of how each cell type regulates progression and/or suppression in tumor microenvironment.…”

“…The analysis from these studies considered absolute blood cell counts rather than the ratio of these cells to understand the mechanism of how each cell type regulates progression and/or suppression in tumor microenvironment. Moreover, these aspects have been actively studied and partially proved in several cancer types 6 , 8 , 15 . However, a detailed study evaluating the clinical significance of each blood cell in patients with HCC remains to be conducted.…”

Systemic immunity markers associated with lymphocytes predict the survival benefit from paclitaxel plus bevacizumab in HER2 negative advanced breast cancer

“…In addition, a low baseline ALC is strongly associated with reduced disease-free survival (DFS) (hazard ratio [HR] 5.24, 95% CI 2.23-12.30, P < 0.001) and OS (HR 6.13, 95% CI 2.21-17.0, P < 0.001) for patients with breast cancer who undergo primary chemotherapy 11,14 . High ALC (≥ 1000/ μL or 1500/µL) was identified as an independent predictive marker for better OS in patients with ABC receiving eribulin therapy 19,20 . In a previous meta-analysis of patients with unselected solid tumors, high NLR was associated with poor OS (HR 1.81, 95% CI 1.67-1.97, P < 0.001).…”

Clinical Utility of Eribulin Mesylate in the Treatment of Breast Cancer: A Chinese Perspective

“…High absolute lymphocyte counts (ALC) have been associated with prolonged survival in patients with MBC treated with eribulin, but not TPC in patients enrolled in the EMBRACE trial. 51 OS was prolonged with eribulin vs TPC in patients with baseline ALC ≥1500/µL (HR, 0.59; 95% CI: 0.437–0.784; P<0.001). However, there was no significant difference by treatment in patients with ALC <1500/µL.…”