Preclinical Evaluation of Liposomal Eribulin (E7389-LF) in a Panel of Sarcoma Patient-Derived Xenograft Models.

Abstract

Sarcomas are rare, heterogeneous tumors with poor prognoses, underscoring the urgent need for novel therapies. Liposomal eribulin (E7389-LF) was developed to improve the efficacy and safety profile of eribulin; however, its preclinical evaluation in sarcomas remains limited. This study aimed to evaluate the clinical applicability of E7389-LF. E7389-LF was comprehensively evaluated and compared with eribulin using 12 patient-derived xenograft (PDX) models representing six sarcoma subtypes. Antitumor activity was assessed across five treatment groups, including independently scaled, clinically relevant regimens of eribulin (0.47 mg/kg) and E7389-LF (0.77 mg/kg). Pharmacokinetic analyses were performed using liquid chromatography-tandem mass spectrometry and fluorescence immunostaining. In addition, correlations between antitumor activity and clinical efficacy were descriptively investigated. Treatment with E7389-LF (0.77 mg/kg) induced tumor regression in 7 of 12 models (58%), compared with 4 of 12 models (33%) treated with eribulin (0.47 mg/kg). Notable responses were observed in rhabdomyosarcoma, Ewing sarcoma, and leiomyosarcoma models. No apparent weight loss was observed in either treatment group. Pharmacokinetic analyses indicated increased systemic and intratumoral drug exposure with E7389-LF. In three PDX models derived from patients treated with eribulin, tumor responses reflected the corresponding clinical outcomes, providing preliminary evidence for the translational relevance of these models. This study demonstrates that E7389-LF exerts antitumor activity broadly comparable to eribulin and exerts antitumor activity in several models across sarcoma PDX models, with favorable tolerability and improved intratumoral drug retention. These findings support the clinical development of E7389-LF for patients with sarcoma who have limited treatment options.