# Assessment of the Mechanisms of Action of Eribulin in Patients with Advanced Liposarcoma Through the Evaluation of Radiological, Functional, and Tissue Responses: A Prospective Monocentric Study (Malibu Study)

## TL;DR

This study explores how eribulin affects tumor vascularization and cell changes in patients with advanced liposarcoma, beyond its known anti-mitotic effects.

## Contribution

The study provides evidence for non-mitotic effects of eribulin in liposarcoma through radiological and histological assessments.

## Key findings

- DCE-MRI showed decreased perfusion in patients with disease control after eribulin treatment.
- Histological changes, including reduced cellularity and vascularization, were observed in most patients.
- Eribulin's non-mitotic effects may contribute to tumor control in a subset of liposarcoma patients.

## Abstract

Eribulin is an antimitotic agent approved for the treatment of patients with advanced liposarcoma. Preclinical studies suggest that it also has a complex antitumor activity, modifying vascularization and tumor cells differentiation in various cancer types. In our prospective study we enrolled patients with pretreated advanced well differentiated/dedifferentiated and myxoid liposarcoma eligible to receive eribulin and we performed a radiological and histological assessment before and after eribulin administration. According to the published data, we found that eribulin shows non-mitotic effects, conferring tumor control in a subgroup of patients with pretreated advanced liposarcoma. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a feasible technique to identify modifications in tumor vascularization.

Background: Liposarcoma (LPS) is one of the most frequent histotypes of soft tissue sarcoma (STS). Eribulin is a cytotoxic agent that has improved overall survival in patients with advanced LPS. Additionally, preclinical and clinical evidence suggests its influence on vascularization and cellular differentiation. Based on these data, we developed this study to investigate non-mitotic effects of eribulin in patients with advanced LPS. Methods: In this prospective monocentric observational study, we included patients with advanced LPS eligible to receive eribulin. An assessment with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and a biopsy were planned before treatment and after four cycles of eribulin. DCE-MRI scans were elaborated to obtain perfusion and permeability maps. Results: From September 2019 to January 2024, 11 patients were enrolled. Among them, 8/11 (73%) had successful pre- and post-treatment assessment. At the time of the analysis, 8/11 (73%) patients had disease progression and 4 (36%) had died, median progression-free survival (mPFS) was 3.3 months, and median overall survival (mOS) was 8.7 months. Among the evaluable patients, DCE-MRI perfusion decreased after eribulin treatment in patients with disease control (partial response or stable disease), while perfusion values increased in patients with progressive disease (PD). No significant change in permeability was found. Post-treatment histological changes were seen nearly in all patients, with decreased cellularity the most common change (50%), followed by vascularization modifications (20%). Conclusions: Eribulin appears to exhibit non-mitotic activity involving both vascularization and cell differentiation in LPS patients. Further studies are needed to better define these effects.