e23555 Background: Angiosarcoma (AS) is a highly aggressive sarcoma. Five-year overall survival (OS) with local disease is only about 60% despite multimodality treatment. In advanced disease, responses to cytotoxic chemotherapy are common; however, median OS is only 3-12 mos. Targeted therapies (TT) have not been consistently effective. Early results for immune checkpoint inhibitors (ICI) are promising but their efficacy has not been compared to chemotherapy. Here we present the outcome of AS patients by systemic regimen and multimodality approach. Methods: We identified 39 patients with pathologically confirmed AS treated at Sylvester Comprehensive Cancer Center and Jackson Memorial Hospital from 2009 to 2019. Clinical characteristics, treatment, responses and survival were analized. We calculated OS using Kaplan-Meier method and statistical significance with Log-Rank Test and Cox regression to estimate hazard ratio (HR) and 95% confidence interval. Progression-free survival (PFS) was analyzed for different regimens in the palliative setting using same approach as for OS. Results: In our cohort, median follow-up is 2.3 years (95% CI = 2 to 3.3), 48% were women and median age at diagnosis was 63 (range 13-89). At presentation, 16 pts (41%) had local disease and 23 advanced or metastatic (59%). By location, 13 pts (33%) had primary cutaneous AS, 12 pts (31%) visceral AS, 5 pts (13%) primary breast AS, 2 (5%) extremity AS and 7 (18%) radiation associated AS. Multimodality treatment was used in 29 pts (74%). OS in the entire cohort at 3 years was 49% (95% CI = 28 to 67%). OS between local disease was (N = 16) and in advanced disease (N = 23) was not statistically significant (p = 0.485; HR = 1.1 [95% CI = 0.4 to 3.3]). In the neoadjuvant setting, objective response rates trended to favor doxorubicin-based regimen (DBR) over taxane-based regimens (TBR) (80% vs. 40%) but were not statistically different (p = 0.519). In the advanced setting, PFS for DBR was 3.9 mo (95% CI 1.1 to 4.9 mo), 5.9 mo for TBR (95% CI 2.3 to 10.9 mo), 6.1 mo for ICI (95% CI not estimable), and 2.4 mo for targeted therapy (TT) (95% CI 0.8 to 8.8 mo), most common TT agent was pazopanib (71% of TT agents). Conclusions: AS is highly aggressive and most patients with local presentation will relapse translating in similar OS to the advanced cohort. No significant activity was seen for TT. In the advanced setting, chemotherapy with TBR appears slightly superior to DBR. ICIs resulted in similar if not superior PFS despite its use in a later line setting. Studies incorporating ICIs into earlier lines of therapy are warranted.