Soft tissue sarcomas are rare cancers with an expected incidence of about 14,000 new cases in 2018, and account for less than 1% of all cancers. It includes in excess of 75 heterogeneous subtypes with varying biology, molecular aberrations, and variable response to treatment. Because of the rarity of these tumors and the many different subtypes, there is no large-scale data to guide treatment, and hence the need for a multidisciplinary individualized approach to treatment, preferably at a high-volume tertiary referral center. For localized disease, surgery with or without radiation is the preferred treatment. In metastatic disease, the longest track record is with use of anthracyclines, either alone or in combination with ifosfamide, but the median overall survival even with combination was just over a year. There have been recent advances in understanding the heterogeneity of these tumors and the need for an individualized approach. With that new knowledge, recent approvals of trabectedin, eribulin, and pazopanib have been limited to some select histologic subtypes with improved outcomes. More recently, immunotherapy has been tested in select histotypes of sarcoma with encouraging activity and has led to further evaluation in combination with immunotherapeutic agents, as well as with chemotherapy and radiation treatments. Here, in this article, we summarize the data of the currently approved therapies in metastatic soft tissue sarcoma, with the principal focus on first-line therapies. We also review the recent encouraging data with PDGFR-targeted antibody (olaratumab) with doxorubicin which showed an impressive improvement in overall survival in phase II study. Molecular characterization of sarcoma subtypes will likely improve understanding of these very diverse tumors and improve target characterization. The ongoing efforts in better understanding these rare tumors hold the key to make a difference in the outcome of these patients.
Keywords: First line treatment; Metastatic soft tissue sarcoma; Targeted therapies.