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.