Established and Experimental Systemic Treatment Options for Advanced Liposarcoma

Abstract

<b><i>Background:</i></b> While soft-tissue sarcomas (STSs) are rare tumors, liposarcomas are among the most common type of STS and are divided into four main subtypes: atypical lipomatous tumor/well-differentiated liposarcoma; dedifferentiated liposarcoma; myxoid/round-cell liposarcoma (MLPS); and pleomorphic liposarcoma (PLPS). The four different subtypes of liposarcomas have varying underlying molecular pathology, clinical behavior, and treatment sensitivity. <b><i>Summary:</i></b> Surgical resection is the mainstay of treatment for patients with localized liposarcoma. Radiotherapy is often used in conjunction with surgery for improving local control of liposarcoma, with MLPS being the most radiosensitive of the four subtypes. For unresectable, advanced, or metastatic disease, the effectiveness of chemotherapy can vary by subtype, with MLPS and PLPS being considered to be chemo-sensitive; however, median survival is low at around 2 years. Current first-line treatment options for patients with liposarcoma include local treatment with or without doxorubicin, ifosfamide, or a doxorubicin-ifosfamide combination, while second-line (and beyond) treatment options include ifosfamide, gemcitabine-based combinations, trabectedin, eribulin, and possibly pazopanib as established therapies. A number of other experimental treatment options are being evaluated, including mouse double minute 2 homolog antagonists, cyclin-dependent kinase 4/6 inhibitors, immune checkpoint modulators, nuclear export inhibitors, multi-kinase inhibitors, peroxisome proliferator-activated receptor gamma agonists, or various combination regimens. This review discusses established systemic therapies and emerging experimental treatment options for the treatment of patients with liposarcoma. <b><i>Key Message:</i></b> New treatments are needed to effectively treat liposarcomas. Results from trials exploring experimental therapeutic options will further define the role that these new treatments will play in the management of the different subtypes of liposarcoma.