New Drug Approvals for Sarcoma in the Last 5 Years

Sarcoma and locally aggressive connective tissue tumors are a complex group of diseases with a growing number of histotypes in the most recent WHO classification. Most of these tumors are rare (incidence <6/105/y) or ultrarare (<1/106/y). Despite their rarity, sarcomas are often good models for the development of personalized medicine, and a large number of new clinical trials in select histotypes and molecular subsets were reported during the past 5 years, leading to a faster rate of new drug approvals. We analyzed the published literature and the abstracts reported in major congresses dedicated to sarcoma and connective tissue tumor management in the last 5 years. Several targeted therapies, cytotoxic treatments, and immunotherapies have demonstrated activity in dedicated histologic and molecular subtypes of sarcomas. The majority of the studies for ultrarare entities are uncontrolled studies, as a consequence of the rarity of histotypes, but randomized controlled trials were available in the less rare histotypes. Most successful trials were based on biomarker selection, which were often driver molecular alterations, while a large number of ongoing research programs aim to identify biomarkers in parallel to new drug development. Availability of the new agents varies across countries. This article describes the new drugs that made it through to the finish line and new agents with promising activity that are in later stages of investigation in the large family of malignant connective tissue tumors.