Current and future systemic treatment options for advanced soft-tissue sarcoma beyond anthracyclines and ifosfamide

Sarcomas are rare, life-threatening, malignant tumors. Surgery is the cornerstone of therapy in the localized setting. About one-third of patients develop distant metastasis. In the metastatic setting, systemic therapy is the mainstay of treatment, and several second-line options are available, proving a modest survival increase for these patients. Trabectedin is an active drug with several described mechanisms of action. Although the objective response rate is low, about one-third of patients achieve disease stabilizations and a prolonged disease control. Interestingly, it has no accumulative toxicities. Pazopanib is the only targeted therapy approved for soft-tissue sarcoma (STS), with the exception of adipocytic sarcoma. Eribulin represents a recently approved therapeutic option for liposarcoma. Other drugs such as gemcitabine combinations, dacarbazine, and taxanes have also shown activity in second lines in advanced STS. The selection should be based on histologic subtype, patient characteristics, and toxicity profile among other factors. This review will summarize clinical development of the current and future therapeutic options for this heterogeneous group of diseases.