Limited activity of metronomic cyclophosphamide and pembrolizumab for soft tissue sarcomas

Outcomes for patients with sarcoma remain poor with overall survival for patients in the metastatic setting typically in the range of 12 to 18 months (1). Programmed death 1 protein (PD-1) has become one of the most important targets in cancer immunotherapy (2), particularly for the many inflammatory cancers that contain PD-1 expressing T cells or cells expressing its ligand (PD-L1) (3). While recent studies have shown that some sarcoma patients may respond to PD-1 blockade, responses are highly subtype specific. Even in highly inflammatory subtypes such as undifferentiated pleomorphic sarcoma (UPS), responses are only seen in a minority of patients demonstrating the need for combination therapies that further improve patient outcome (4).