The challenge of running trials in advanced angiosarcoma: A systematic review of the literature from EORTC/STBSG to guide the development of angiosarcoma-specific trials

Introduction While available systemic treatments have modest long term efficacy in advanced angiosarcoma, immunotherapy represents an interesting new therapeutic opportunity. To establish its benefit, it is required to conduct a clinical trial assessing its efficacy and toxicity compared to standard treatments. Material and methods This is a literature review from PubMed search. Results Several systemic treatments (chemotherapy and TKI) are currently used in advanced angiosarcoma with ORR ranging from 12.5 to 68 % and PFS from 2 to 7 months. However, few randomized trials, mainly phase II, has been conducted to compare these treatments. While most centers propose doxorubicin containing regimens or paclitaxel in 1st or 2nd line, a high heterogeneity of regimens administered in this setting is observed even across sarcoma specialized centers with no consensual standard treatment. Encouraging signals of immunotherapy activity have been reported in angiosarcoma from several retrospective and phase II studies assessing anti-PD1 either alone or in combination with anti CTLA4 or TKI. Although cutaneous and head and neck location seems to benefit more from immunotherapy, response may be observed in any angiosarcoma subtype. In sarcoma in general and AS in particular, no biomarker has been clearly established to predict the efficacy of immunotherapy: high tumor mutational burden and presence of tertiary lymphoid structures are under assessment. Discussion Even essential, developing a randomized clinical trial in AS struggles with the heterogeneity of the disease, the lack of consensual standard regimen, the uncertainty on optimal immunotherapy administration and the absence of established predictive biomarkers. Conclusion International collaboration is essential to run randomized trial in advanced AS and asses the efficacy of immune therapy in this rare and heterogeneous disease.