Immunotherapy and Targeted Therapies in Sarcoma: Proposed Synergy with Combination Treatment.

Abstract

The combination of targeted therapies and immunotherapies for advanced and metastatic sarcomas has been proposed owing to the enhanced effect of antiangiogenic therapies on the tumor microenvironment. We found eight studies published to date assessing the effectiveness of combined multitargeted vascular endothelial growth factor (VEGF)-tyrosine kinase inhibitors with immune checkpoint inhibitors (ICIs) in sarcoma. It is difficult to draw conclusions owing to limited data and primarily single-arm studies, although initial literature appears promising and requires further study. It remains unknown which sarcoma subtypes may derive the most benefit owing to the limited literature. Benefit was seen primarily in angiosarcoma (AS) and alveolar soft part sarcoma (ASPS), as well as in other tumor subtypes, with few patients achieving complete response (CR). The patients who achieved CRs had desmoplastic small round cell tumor (DSRCT), AS, and chondrosarcoma (CS). Mixed results were found in patients with leiomyosarcoma (LMS), gastrointestinal stromal tumor (GIST), and bone sarcomas, although combination therapy appears to be less effective in these subtypes. Further studies are required to explore optimal treatment agents and dosing strategies to improve both efficacy and tolerability. Although initial results are promising in select patients, phase 3 randomized controlled trials are necessary to determine true treatment effect with combination therapy versus VEGF-inhibitor or ICI alone.