Programmed cell death 1 protein and programmed death-ligand 1 inhibitors in the treatment of nonmelanoma skin cancer: A systematic review

Background Immunotherapy using programmed cell death 1 protein (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors has been increasingly reported in a variety of nonmelanoma skin cancers (NMSCs). Objective To analyze the evidence of PD-1 and PD-L1 inhibitors in the treatment of NMSC. Methods A primary literature search was conducted with the PubMed, Cochrane Library, EMBASE, Web of Science, and CINAHL databases through October 28, 2018, to include studies on the use of PD-1 or PD-L1 inhibitors in patients for NMSC. Two reviewers independently performed study selection, data extraction, and critical appraisal. Results This systematic review included 51 articles. The most robust evidence was in the treatment of Merkel cell carcinoma and cutaneous squamous cell carcinomas, as supported by phase 1 and 2 clinical trials. Treatment of basal cell carcinoma, cutaneous sarcoma, sebaceous carcinoma, and malignant peripheral nerve sheath tumor also showed benefit with PD-1/PD-L1 inhibitors, but data are limited. There does not appear to be efficacy for PD-1/PD-L1 inhibitors in cutaneous lymphomas. Limitations More investigation is needed to determine the efficacy, tumor responsiveness, and the safety profile of PD-1 and PD-L1 inhibitors in NMSC. Conclusion PD-1 and PD-L1 inhibitors exhibit treatment efficacy in a variety of NMSCs.