Recent Advances in the Treatment of Metastatic Soft Tissue Sarcoma

Soft tissue sarcomas (STS) are a rare group of heterogeneous malignancies with >50 histologic subtypes that have varying biological behaviour and responsiveness to systemic therapy. The mainstay of therapy for metastatic STS in recent decades has been doxorubicin. To improve survival outcomes, numerous agents have been combined with doxorubicin; however, no combination has led to a survival benefit over doxorubicin alone until the recent use of olaratumab, a monoclonal antibody targeting platelet-derived growth factor-α. In addition to olaratumab, several other new drugs have surfaced as promising treatment options. Marine-derived chemotherapy agents, eribulin and trabectedin, are active in selecting STS subtypes. Both agents are effective in liposarcoma, while trabectedin also has activity in leiomyosarcoma. Further understanding of the importance of STS subtype-directed therapy, as well as the genomic complexities of STS, has led to development of several small molecule inhibitors for specific STS histologies. Agents targeting vascular endothelial growth factors, platelet-derived growth factors, and cyclin-dependent kinases 4 and 6 have all shown some efficacy in various STS subtypes. Similar to the selective activity of cytotoxic agents and small molecule inhibitors, immunotherapy, which has revolutionised management of numerous cancers, has also demonstrated activity in select STS subtypes. Collectively, these novel therapies highlight the importance of histology-directed approaches and of a greater understanding of the genomic landscape of STS. This review describes advances in chemotherapy, molecularly targeted, and immunotherapy agents for STS.