(P 452) EFFECTIVENESS OF ERIBULIN FOR MYXOID PLEOMORPHIC LIPOSARCOMA: INSIGHTS FROM A PATIENT-DERIVED MODEL AND CLINICAL TRANSLATION IN A PATIENT WITH ADVANCED DISEASE

Objective: Myxoid pleomorphic liposarcoma (MPL) is an ultra-rare soft tissue sarcoma primarily affecting children and adolescents. This study investigates the effectiveness of systemic therapeutic options for MPL by correlating findings from a patient-derived model with observations in a patient with advanced, widespread metastatic disease.

Methods: A patient-derived xenograft (PDX) and a paired cell line was established from a primary MPL. Drug activity was quantified as maximum tumor volume inhibition percentage (max TVI%). We evaluated a patient with advanced MPL who had experienced disease progression despite multiple prior lines of systemic treatment and surgical interventions.

Results: Eribulin achieved complete tumor response (max TVI 100%) in all treated PDX models. While six tumors regrew approximately 50 days post-treatment, one tumor exhibited a complete histopathological response. Single-agent doxorubicin (max TVI 87%) and ifosfamide (max TVI 94%), as well as their combination (max TVI 97%) showed meaningful activity but tumor regrowth occurred in all mice. Trabectedin (max TVI 67%) and selinexor (max TVI 55%) exhibited limited effectiveness. The differences in tumor response to eribulin seems to rely on the ability of the drug to induce programmed cell death in terms of apoptosis and necroptosis, as observed at western blot and RNA-seq analysis. Based on these preclinical findings, the patient with progressive MPL, who had undergone extensive prior treatments, was initiated on eribulin. This patient achieved disease stability for 11 cycles (January-October 2024) with symptom improvement before disease progression was observed.

Conclusion: Eribulin emerged as the most effective treatment option in a patient-derived preclinical model of MPL. These preclinical results were successfully translated to a patient with advanced disease, who experienced a significant period of disease stability after multiple prior therapeutic lines.