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
Open Access
- 4 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Breast Cancer
- Vol. 27 (4), 706-715
- https://doi.org/10.1007/s12282-020-01067-2
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/mu l (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/mu l (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/mu l 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.Keywords
Funding Information
- Eisai Inc., Woodcliff Lake, NJ, USA
This publication has 20 references indexed in Scilit:
- PD-L1 is a novel direct target of HIF-1α, and its blockade under hypoxia enhanced MDSC-mediated T cell activationThe Journal of Experimental Medicine, 2014
- Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial–mesenchymal transition (EMT) to mesenchymal–epithelial transition (MET) statesBritish Journal of Cancer, 2014
- Usefulness of Pretreatment Neutrophil to Lymphocyte Ratio in Predicting Disease-Specific Survival in Breast Cancer PatientsJournal of Breast Cancer, 2013
- Clinical Impact of Tumor-infiltrating Lymphocytes for Survival in Curatively Resected Stage IV Colon Cancer with Isolated Liver or Lung MetastasisAnnals of Surgical Oncology, 2012
- Tumor-infiltrating lymphocytes predict response to chemotherapy in patients with advance non-small cell lung cancerCancer Immunology, Immunotherapy, 2012
- Tumor-infiltrating lymphocytes and dendritic cells in human colorectal cancer: Their relationship to KRAS mutational status and disease recurrenceHuman Immunology, 2011
- Role of TGF-β and the Tumor Microenvironment During Mammary TumorigenesisGene Expression, 2011
- Eribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised studyThe Lancet, 2011
- Single‐institution experience with ipilimumab in advanced melanoma patients in the compassionate use settingCancer, 2010
- TRANSFORMING GROWTH FACTOR-β REGULATION OF IMMUNE RESPONSESAnnual Review of Immunology, 2006