Cutaneous angiosarcomas (cAS) represent a particularly challenging sarcoma subtype that frequently occurs in pretreated patients as a consequence of radiation therapy or chronic lymphedema. Local treatments are complicated as affected sites are often compromised by previous surgery and irradiation and tumor lesions lack a clear delineation. Novel treatments are therefore urgently needed to improve the outcome of these patients.
We identified 130 angiosarcomas from our institutional database of which 37 originated in the skin. Clinical characteristics and outcome was analyzed and available tumor tissue was tested for expression of PD-L1 and infiltration of immune cells, including CD8+ cells.
Response to classical chemotherapeutic drugs was highest for taxanes, but frequent responses were also seen with liposomal doxorubicin, gemcitabine or oral cyclophosphamide. Despite promising chemotherapy responses, most patients eventually died of disease with often dismal local complications. Using IHC we observed several cases of cAS that showed a significant expression of PD-L1 between 10-20% on tumor cells. In addition, infiltration of immune cells with the presence of CD8+ cells was regularly observed. One of the patients with PD-L1-positive angiosarcoma of the scalp who had progressed after several lines of chemotherapy was treated with pembrolizumab. Following the second application the patient already showed a dramatic improvement of symptoms with complete healing of a large area of ulcerating and bleeding skin and ongoing remission after 6 months of treatment.
Based on this study, PD-L1-directed therapy may represent a particular opportunity for angiosarcomas of the skin given the frequency of PD-L1 expression and infiltration of immune cells. Our findings suggest prospective immunotherapy studies in this sarcoma subtype.
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Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
M. Schuler: Funding, honoraria and reimbursements from Alexion, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly, MSD, Novartis, AstraZeneca, Roche. H-U. Schildhaus: Honoraria and reimbursements from MSD, BMS, Roche, Abbott Molecular and ZytoVision. S. Bauer: Funding, honoraria and reimbursements from Novartis, Pfizer, Bayer, PharmaMar, GlaxoSmithKline, Blueprint Medicines, Lilly, Deciphera Pharmaceuticals. All other authors have declared no conflicts of interest.