Cutaneous angiosarcoma: A review of current evidence for treatment with checkpoint inhibitors

Abstract

Cutaneous angiosarcoma (cAS) is a rare and aggressive subtype of soft tissue sarcoma with poor prognosis and suboptimal treatment options. Clinical presentation is variable, but cAS often arises from the head and neck. The most widely accepted current approach, surgical excision with adjuvant radiotherapy, is associated with high recurrence rates and can leave patients with profound disfigurement. Chemotherapy and targeted therapy alternatives have had limited success. Thus, there is a significant unmet need to address the absence of durable treatments for advanced and metastatic cAS. Like melanoma and cutaneous squamous cell carcinoma, tumor types with known response to immunotherapy, cAS harbors immune biomarkers, such as tumor mutational burden high (TMB-H), PD-L1 positivity, ultraviolet signature expression, and tertiary lymphoid structures. While data on the use and efficacy of immunotherapy in cAS is limited, the biomarkers suggest a promising advancement in future treatment options. This review aims to summarize and discuss current data from case reports, case series, retrospective studies and clinical trials regarding immunotherapy treatment and outcomes for cAS.

Angiosarcoma: clinical outcomes and prognostic factors, a single-center analysis

“…The aforementioned similarity in mutational patterns of head and neck AS to melanomas and the proven efficacy of immune checkpoint inhibition in melanomas and in multiple other cancer types with high tumor mutational burden lay a valuable foundation for future studies ( 25 , 27 , 28 , 33 ). Several smaller studies reported durable responses with checkpoint inhibitors in the treatment of AS ( 34 – 36 ). An ongoing multi-center Scandinavian phase 2 study is examining this rationale using pembrolizumab combined with the beta-blocker propranolol for advanced AS or undifferentiated pleomorphic sarcoma to study the effect on progression-free survival ( 37 ).…”

Advancing Cancer Research: Current Knowledge on Cutaneous Neoplasia

“…Recently, propranolol treatment or immunotherapy were proposed for CAS management [ 107 ]. There are also studies showing that patients with angiosarcoma may benefit from anti-PD-1 (programmed death ligand-1) therapy or anti-tumor mutational burden high (TMB-H) [ 107 , 116 , 117 ].…”

A commentary on ‘Electrochemotherapy for advanced cutaneous angiosarcoma: A European register-based cohort study from the International Network for Sharing Practices of electrochemotherapy (InspECT)’

“…Angiosarcomas, which account for 1–2% of all head and neck sarcomas, are extremely rare malignancies that penetrate local structures through anaplastic vascular or lymphatic cells 1 , 2 . Campana et al .…”