Indices of peripheral leukocytes predict longer overall survival in breast cancer patients on eribulin in Japan.
Administration, Intravenous
Adult
Aged
Breast Neoplasms
/ blood
Female
Follow-Up Studies
Furans
/ administration & dosage
Humans
Japan
/ epidemiology
Ketones
/ administration & dosage
Lymphocyte Count
Middle Aged
Neutrophils
Proportional Hazards Models
Receptor, ErbB-2
Tubulin Modulators
/ administration & dosage
Breast neoplasms
Eribulin
Japan
Product surveillance
Survival
post-marketing
Journal
Breast cancer (Tokyo, Japan)
ISSN: 1880-4233
Titre abrégé: Breast Cancer
Pays: Japan
ID NLM: 100888201
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
24
11
2020
accepted:
22
02
2021
pubmed:
8
3
2021
medline:
16
12
2021
entrez:
7
3
2021
Statut:
ppublish
Résumé
It was reported that eribulin regulates the tumor microenvironment, including the immune system, by inducing vascular remodeling. Lymphocyte counts are a critical index of immune response in patients. The non-Asian, global EMBRACE study has suggested that baseline absolute lymphocyte count (ALC) may be a predictor of the survival benefit of eribulin in breast cancer patients. We examined whether the baseline ALC is a potential predictor of overall survival (OS) in Japanese patients with HER2-negative advanced breast cancer treated with eribulin. This was a post hoc analysis of data from a post-marketing observational study of eribulin in Japan. The OS by baseline ALC was estimated using the Kaplan-Meier method, with the cut-off value of 1500/μL for ALC. The OS by baseline neutrophil-to-lymphocyte ratio (NLR), a general prognostic index in breast cancer patients, was also estimated, with the cut-off value of 3. The median OS was longer in patients with an ALC of ≥ 1500/μL than in those with an ALC of < 1500/μL (19.4 vs. 14.3 months; hazard ratio [HR]: 0.628; 95% confidence interval [CI]: 0.492, 0.801). Patients with an NLR of ≥ 3 showed shorter OS than those with an NLR of < 3 (13.2 vs. 18.8 months; HR: 1.552; 95% CI 1.254, 1.921), and NLR also separated OS in patients with an ALC of < 1500/μL. Consistent with the findings of a previous study involving a non-Asian, Western population, our study suggested that baseline ALC may be a predictive factor for the survival benefit of eribulin in Japanese patients.
Sections du résumé
BACKGROUND
BACKGROUND
It was reported that eribulin regulates the tumor microenvironment, including the immune system, by inducing vascular remodeling. Lymphocyte counts are a critical index of immune response in patients. The non-Asian, global EMBRACE study has suggested that baseline absolute lymphocyte count (ALC) may be a predictor of the survival benefit of eribulin in breast cancer patients. We examined whether the baseline ALC is a potential predictor of overall survival (OS) in Japanese patients with HER2-negative advanced breast cancer treated with eribulin.
METHODS
METHODS
This was a post hoc analysis of data from a post-marketing observational study of eribulin in Japan. The OS by baseline ALC was estimated using the Kaplan-Meier method, with the cut-off value of 1500/μL for ALC. The OS by baseline neutrophil-to-lymphocyte ratio (NLR), a general prognostic index in breast cancer patients, was also estimated, with the cut-off value of 3.
RESULTS
RESULTS
The median OS was longer in patients with an ALC of ≥ 1500/μL than in those with an ALC of < 1500/μL (19.4 vs. 14.3 months; hazard ratio [HR]: 0.628; 95% confidence interval [CI]: 0.492, 0.801). Patients with an NLR of ≥ 3 showed shorter OS than those with an NLR of < 3 (13.2 vs. 18.8 months; HR: 1.552; 95% CI 1.254, 1.921), and NLR also separated OS in patients with an ALC of < 1500/μL.
CONCLUSIONS
CONCLUSIONS
Consistent with the findings of a previous study involving a non-Asian, Western population, our study suggested that baseline ALC may be a predictive factor for the survival benefit of eribulin in Japanese patients.
Identifiants
pubmed: 33677779
doi: 10.1007/s12282-021-01232-1
pii: 10.1007/s12282-021-01232-1
pmc: PMC8213560
doi:
Substances chimiques
Furans
0
Ketones
0
Tubulin Modulators
0
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
eribulin
LR24G6354G
Types de publication
Journal Article
Observational Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
945-955Références
Cortes J, O’Shaughnessy J, Loesch D, Blum JL, Vahdat LT, Petrakova K, et al. Eribulin monotherapy versus treatment of physician’s choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study. Lancet. 2011;377:914–23.
doi: 10.1016/S0140-6736(11)60070-6
Kaufman PA, Awada A, Twelves C, Yelle L, Perez EA, Velikova G, et al. Phase III open-label randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2015;33:594–601.
doi: 10.1200/JCO.2013.52.4892
Watanabe J, Ito Y, Ohsumi S, Mizutani M, Tashiro H, Sakurai K, et al. Safety and effectiveness of eribulin in Japanese patients with locally advanced or metastatic breast cancer: a post-marketing observational study. Invest New Drugs. 2017;35:791–9.
doi: 10.1007/s10637-017-0486-4
Tsurutani J, Sakata Y, Matsuoka T. Chemotherapy-induced peripheral neuropathy in breast cancer patients treated with eribulin: interim data from a post-marketing observational study. Breast Cancer. 2019;26:235–43.
doi: 10.1007/s12282-018-0919-8
Inoue K, Takahashi M, Mukai H, Yamanaka T, Egawa C, Sakata Y, et al. Effectiveness and safety of eribulin in Japanese patients with HER2-negative, advanced breast cancer: a 2-year post-marketing observational study in a real-world setting. Invest New Drugs. 2020;38:1540–9.
doi: 10.1007/s10637-019-00890-5
Miyagawa Y, Araki K, Bun A, Ozawa H, Fujimoto Y, Higuchi T, et al. Significant association between low baseline neutrophil-to-lymphocyte ratio and improved progression-free survival of patients with locally advanced or metastatic breast cancer treated with eribulin but not with Nab-paclitaxel. Clin Breast Cancer. 2018;18:400–9.
doi: 10.1016/j.clbc.2018.03.002
Miyoshi Y, Yoshimura Y, Saito K, Muramoto K, Sugawara M, Alexis K, et al. 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;27:706–15.
doi: 10.1007/s12282-020-01067-2
Yoshida T, Ozawa Y, Kimura T, Sato Y, Kuznetsov G, Xu S, et al. Eribulin mesilate suppresses experimental metastasis of breast cancer cells by reversing phenotype from epithelial-mesenchymal transition (EMT) to mesenchymal–epithelial transition (MET) states. Br J Cancer. 2014;110:1497–505.
doi: 10.1038/bjc.2014.80
Funahashi Y, Okamoto K, Adachi Y, Semba T, Uesugi M, Ozawa Y, et al. Eribulin mesylate reduces tumor microenvironment abnormality by vascular remodeling in preclinical human breast cancer models. Cancer Sci. 2014;105:1334–42.
doi: 10.1111/cas.12488
Ueda S, Saeki T, Takeuchi H, Shigekawa T, Yamane T, Kuji I, et al. In vivo imaging of eribulin-induced reoxygenation in advanced breast cancer patients: a comparison to bevacizumab. Br J Cancer. 2016;114:1212–8.
doi: 10.1038/bjc.2016.122
Ito K, Hamamichi S, Abe T, Akagi T, Shirota H, Kawano S, et al. Antitumor effects of eribulin depend on modulation of the tumor microenvironment by vascular remodeling in mouse models. Cancer Sci. 2017;108:2273–80.
doi: 10.1111/cas.13392
Zhao S, Yu W, Ukon N, Tan C, Nishijima KI, Shimizu Y, et al. Elimination of tumor hypoxia by eribulin demonstrated by 18F-FMISO hypoxia imaging in human tumor xenograft models. EJNMMI Res. 2019;9:51.
doi: 10.1186/s13550-019-0521-x
Goto W, Kashiwagi S, Asano Y, Takada K, Morisaki T, Fujita H, et al. Eribulin promotes antitumor immune responses in patients with locally advanced or metastatic breast cancer. Anticancer Res. 2018;38:2929–38.
pubmed: 29715119
Ray-Coquard I, Cropet C, Van Glabbeke M, Sebban C, Le Cesne A, Judson I, et al. Lymphopenia as a prognostic factor for overall survival in advanced carcinomas, sarcomas, and lymphomas. Cancer Res. 2009;69:5383–91.
doi: 10.1158/0008-5472.CAN-08-3845
Koh CH, Bhoo-Pathy N, Ng KL, Jabir RS, Tan GH, See MH, et al. Utility of pre-treatment neutrophil-lymphocyte ratio and platelet-lymphocyte ratio as prognostic factors in breast cancer. Br J Cancer. 2015;113:150–8.
doi: 10.1038/bjc.2015.183
Araki K, Ito Y, Fukada I, Kobayashi K, Miyagawa Y, Imamura M, et al. Predictive impact of absolute lymphocyte counts for progression-free survival in human epidermal growth factor receptor 2-positive advanced breast cancer treated with pertuzumab and trastuzumab plus eribulin or nab-paclitaxel. BMC Cancer. 2018;18:982.
doi: 10.1186/s12885-018-4888-2
Watanabe J, Saito M, Horimoto Y, Nakamoto S. A maintained absolute lymphocyte count predicts the overall survival benefit from eribulin therapy, including eribulin re-administration, in HER2-negative advanced breast cancer patients: a single-institutional experience. Breast Cancer Res Treat. 2020;181:211–20.
doi: 10.1007/s10549-020-05626-1
Ueno A, Maeda R, Kin T, Ito M, Kawasaki K, Ohtani S. Utility of the absolute lymphocyte count and neutrophil/lymphocyte ratio for predicting survival in patients with metastatic breast cancer on eribulin: a real-world observational study. Chemotherapy. 2019;64:259–69.
doi: 10.1159/000507043
Myojin M, Horimoto Y, Ito M, Kitano S, Ishizuka Y, Sasaki R, et al. Neutrophil-to-lymphocyte ratio and histological type might predict clinical responses to eriburin-based treatment in patients with metastatic breast cancer. Breast Cancer. 2020;27:732–8.
doi: 10.1007/s12282-020-01069-0
Ivars Rubio A, Yufera JC, de la Morena P, Fernández Sánchez A, Navarro Manzano E, García Garre E, et al. Neutrophil-lymphocyte ratio in metastatic breast cancer is not an independent predictor of survival, but depends on other variables. Sci Rep. 2019;9:16979.
doi: 10.1038/s41598-019-53606-3
Diehl A, Yarchoan M, Hopkins A, Jaffee E, Grossman SA. Relationships between lymphocyte counts and treatment-related toxicities and clinical responses in patients with solid tumors treated with PD-1 checkpoint inhibitors. Oncotarget. 2017;8:114268–80.
doi: 10.18632/oncotarget.23217
Muto Y, Kitano S, Tsutsumida A, Namikawa K, Takahashi A, Nakamura Y, et al. Investigation of clinical factors associated with longer overall survival in advanced melanoma patients treated with sequential ipilimumab. J Dermatol. 2019;46:498–506.
doi: 10.1111/1346-8138.14865
Ku GY, Yuan J, Page DB, Schroeder SE, Panageas KS, Carvajal RD, et al. Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: lymphocyte count after 2 doses correlates with survival. Version 2. Cancer. 2010;116:1767–75.
doi: 10.1002/cncr.24951
Kashiwagi S, Asano Y, Goto W, Takada K, Morisaki T, Kouhashi R, et al. Validation of systemic and local tumour immune response to eribulin chemotherapy in the treatment of breast cancer. Anticancer Res. 2020;40:3345–54.
doi: 10.21873/anticanres.14317
Taylor MA, Lee YH, Schiemann WP. Role of TGF-beta and the tumor microenvironment during mammary tumorigenesis. Gene Expr. 2011;15:117–32.
doi: 10.3727/105221611X13176664479322