Immune Checkpoint Inhibitors for Treating Advanced Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (CSCC) is one of the most common human malignancies, and the incidence is increasing with time. High mutational loads, known infiltration with lymphocytes, and programmed death (PD)-ligand 1 (PD-L1) expression suggest that immune checkpoint inhibitors, such as PD-1 inhibitors, may show utility in treating CSCC, similar to response see in other solid tumor types. Recently, the robust responsiveness of CSCCs to the PD-1 inhibitor cemiplimab was revealed in the results of a combined phase I/II clinical trial, with an overall response rate of 50% and a durable response exceeding 6 months in 57% of responders. Compared to prior systemic therapies with scant data for efficacy and safety, cemiplimab is a breakthrough therapy, the first systemic drug approved for advanced CSCCs. Other immune checkpoint inhibitors have shown promise through case reports and series, and are currently in clinical development for CSCCs.