Angiosarcoma: adaptive designs leveraging vascular biology and antiangiogenic repurposing

Angiosarcoma is a rare and aggressive vascular malignancy characterized by substantial clinical and molecular heterogeneity. Grouping UV-associated cutaneous, radiation-associated, and visceral tumors within unselected clinical trials may obscure treatment effects in biologically distinct subgroups.

This narrative review examines cytotoxic and anti-angiogenic therapy, immunotherapy, oncolytic virotherapy, non-canonical vascular targets, and advances in multiomic, spatial, and proteomic profiling. It also evaluates adaptive and Bayesian trial designs as strategies for biomarker-enriched development. Literature was identified through PubMed and AI-assisted discovery, with relevant clinical trial reports, conference abstracts, and regulatory guidance included through July 2026.

Current systemic therapies provide modest population-level benefit and generally limited durability. Emerging evidence supports biologically distinct treatment-responsive subsets, including selected UV-associated cutaneous and secondary angiosarcomas, although validated predictive biomarkers remain lacking. Progress will require integration of molecular, immune, spatial, and protein-level features into patient selection. Adaptive and enrichment-based trial designs may reduce dilution of subgroup-specific signals and support the transition from histology-defined cohorts toward mechanistically stratified treatment.