SY9-2 - Treatment strategy for advanced soft tissue sarcoma

Abstract

Soft tissue sarcoma (STS) is a rare tumor with more than 50 histologic subtypes. Many types of STS are not sensitive to chemotherapy, so patients with advanced diseases have poor prognosis. Development of novel anticancer therapy is in urgent need. Doxorubicin monotherapy is currently the standard first line treatment of advanced STS, but there is no standard for second line therapy. Recently, three new drugs: pazopanib, trabectedin, and eribulin have been approved for the second line treatment of patients with advanced STS, but the best treatment sequence of those drugs are not known. Sensitivity of STS to each drug seems to vary by histologic subtypes. For instance, liposarcoma seems be more sensitive to eribulin and less sensitive to pazopanib. Translocation related sarcoma (TRS) such as myxoid liposarcoma seems to be sensitive to trabectedin. Furthermore, these drugs have different safety profiles, so subtypes and patient characteristics must be considered for treatment selection. Development of specific molecular target therapy for each type of STS is necessary. There are specific chromosome translocations in 20-30% of STS, but their products are mostly transcriptional factors, and target therapy for those factors are difficult to develop. Trabectedin inhibits function of transcriptional factors, and shows higher efficacy for TRS. As molecular target therapies for gene mutations, success in molecular target therapy for c-kit and PDGFR mutation in gastrointestinal stromal tumor was followed by efficacy for rare sarcomas such as inflammatory myofibroblastic tumor or dermatofibrosarcoma protuberans, but there are few developments in other sarcomas. STS are associated with angiogenesis to a greater or lesser extent, so angiogenesis inhibitors such as pazopanib show good efficacy in some subtypes. Immune checkpoint inhibitors also have been developed for STS and show some efficacy in subtypes such as undifferentiated pleomorphic sarcoma.