In vivo imaging of eribulin-induced reoxygenation in advanced breast cancer patients: A comparison to bevacizumab

Abstract

Background: Eribulin mesylate (eribulin) is a first-in-class halichondrin B-based microtubule dynamics inhibitor. To compare the anti-angiogenic activity of eribulin to that of bevacizumab, we compared tumour vessel remodelling and reoxygenation between the two agents.Methods:Patients with advanced breast cancer with stage III/IV were eligible for the study. Patients were assigned to receive either eribulin or single-agent bevacizumab. Tissue concentrations of oxyhaemoglobin (O 2 Hb) and deoxyhaemoglobin (HHb), and oxygen saturation (SO 2) of breast tumours before and day 7 after the first infusion were repeatedly measured using diffuse optical spectroscopic imaging (DOSI). A pair of blood samples was collected for multiplex biomarker studies.Results:Baseline DOSI measurement of all 29 patients (eribulin, n=14 and bevacizumab, n=15) revealed significantly higher tumour concentrations of O 2 Hb and HHb than that in the normal breast tissue. After eribulin treatment, DOSI revealed a significant decrease in HHb concentration and increased SO 2 during the observation period. This trend was not observed for bevacizumab. Instead, bevacizumab significantly decreased the concentration of O 2 Hb. The multiplex biomarker study revealed that both eribulin and bevacizumab decreased plasma concentrations of VEGF and bFGF, but only eribulin treatment suppressed the plasma concentration of TGF-β1.Conclusions:Eribulin, but not bevacizumab, treatment increased tumour SO 2. Suppression of TGF-β1 by eribulin could have a favourable anti-angiogenic effect. Our results suggest that differences in vascular remodelling between these two agents may account for their different effects on tumour reoxygenation.