Angiosarcoma: adaptive designs leveraging vascular biology and antiangiogenic repurposing

Area of Science:

• Oncology
• Vascular Biology
• Clinical Trial Design

Background:

• Angiosarcoma is a rare, aggressive vascular malignancy with considerable clinical and molecular heterogeneity.
• Current unselected clinical trials may obscure treatment effects in distinct biological subgroups, such as UV-associated cutaneous, radiation-associated, and visceral tumors.

Purpose of the Study:

• To review current and emerging therapies for angiosarcoma, including cytotoxic, anti-angiogenic, and immunotherapies.
• To explore advances in multiomic, spatial, and proteomic profiling for angiosarcoma.
• To evaluate adaptive and Bayesian trial designs for biomarker-enriched development in angiosarcoma.

Main Methods:

• Narrative review of literature identified through PubMed and AI-assisted discovery.
• Inclusion of clinical trial reports, conference abstracts, and regulatory guidance up to July 2026.
• Examination of cytotoxic and anti-angiogenic therapy, immunotherapy, oncolytic virotherapy, and non-canonical vascular targets.

Main Results:

• Current systemic therapies offer modest population-level benefit with limited durability.
• Emerging evidence suggests biologically distinct, treatment-responsive subsets exist, including certain UV-associated cutaneous and secondary angiosarcomas.
• Validated predictive biomarkers for these subsets are currently lacking.

Conclusions:

• Progress in angiosarcoma treatment requires integrating molecular, immune, spatial, and protein-level features for patient selection.
• Adaptive and enrichment-based trial designs can mitigate subgroup signal dilution.
• These designs support a shift from histology-defined cohorts to mechanistically stratified treatment approaches.