(P 124) ASSESSMENT OF THE MECHANISMS OF ACTION OF ERIBULIN IN PATIENTS WITH ADVANCED LIPOSARCOMA THROUGH THE EVALUATION OF THE RADIOLOGICAL, FUNCTIONAL AND TISSUE RESPONSE: A MONOCENTRIC PROSPECTIVE STUDY

Objective: Eribulin mesylate (eribulin) is a microtubule-targeting cytotoxic agent that has demonstrated improved overall survival in pretreated breast cancer patients and liposarcoma patients. Additionally, preclinical studies and a small clinical study have indicated that eribulin may exert non-mitotic effects such as influencing vascularization and cellular differentiation. Based on these data, we conducted this study to assess clinical, radiological and histological effects of eribulin in patients with advanced liposarcoma (LPS), with a particular focus on non-mitotic mechanisms of action.

Methods: In this prospective monocentric observational study we included patients with advanced (inoperable or metastatic) LPS who had received prior chemotherapy for advanced disease and were eligible to receive eribulin. A radiologic assessment with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and a histologic assessment (biopsy) were planned before treatment and after 4 cycles of eribulin. DCE-MRI scans were elaborated to obtain perfusion and permeability maps. These two parameters were specifically analyzed in the biopsy site, in the areas respectively with more aggressive and less aggressive radiological aspects and in a control area (normal fat tissue).

Results: From September 2019 to January 2024, a total of 11 patients were enrolled, the majority of whom presented with a primary tumor site in the retroperitoneum. Among them, 8 (73%) managed to undergo both pre- and post-treatment assessment. Patients were heavily pretreated, being median time from diagnosis to the start of eribulin 69.6 months; moreover, 73% had received local treatments for recurrent/metastatic disease. At the time of the analysis 73% of patients had disease progression and 36% had died. Among the first group one patient had stable disease in the examined target lesions but disease progression because of a new distant metastasis. In the overall population, median progression-free survival (mPFS) was 3.3 months, while median overall survival (mOS) was 8.7 months. In patients with disease control (partial response or stable disease) mPFS was 16.5 months and mOS was 16.5 months. Among the evaluable patients, we found a trend in DCE-MRI perfusion decrease after eribulin treatment in patients with disease control, while perfusion values increased in patients with progressive disease (PD). No evident trend in permeability was found. As for histological assessment, post-treatment changes were seen in all patients except for one patient that had low grade disease (predominantly well-differentiated liposarcoma). Cellularity decrease was the most common detected change, being reported in 50% of patients (both in patients with disease control or PD). On the other hand, vascularization modifications were detected in 25% of patients. Interestingly, signs of adipose differentiation and maturation were found in three (37.5%) patients, one of whom had radiological disease progression.

Conclusion: Eribulin exhibits non-mitotic activity concerning both vascularization and cell differentiation in LPS patients. Further studies are needed to better define these mechanisms of action and to identify patients that could benefit the most from eribulin.