PD-1 Inhibitors in Orbital and Periocular Squamous Cell Carcinoma: A Review

Periocular and orbital cutaneous squamous cell carcinoma (cSCC) poses significant therapeutic challenges due to its proximity to critical ocular structures and risk of local invasion. Conventional treatments such as surgery and radiotherapy can result in substantial morbidity, especially in cases requiring orbital exenteration. Recently, immune checkpoint inhibitors targeting programmed cell death protein-1 (PD-1) have emerged as a novel treatment option for advanced and refractory cSCC. This study aims to systematically review the clinical application, efficacy, and safety of PD-1 inhibitors in the treatment of periocular and orbital cSCC.

A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Web of Science, Embase, and Cochrane Central were searched in June 2025 for studies reporting outcomes of PD-1 inhibitor therapy in periocular or orbital cSCC. Eligible studies included case reports, case series, and clinical trials. Extracted data included patient demographics, tumor characteristics, treatment regimens, outcomes, and adverse events.

Thirty-three studies met inclusion criteria, describing 102 patients treated with PD-1 inhibitors, primarily cemiplimab and pembrolizumab. Therapy was used as first-line or after failure of conventional treatments. Overall, 52% of patients achieved complete response, 34% partial response, 7% stable disease, and 7% progressive disease. Treatment was generally well tolerated; 40 patients experienced adverse events, most commonly fatigue, diarrhea, and rash. One fatal myocarditis case and 2 cases of diabetic ketoacidosis were reported. Mean follow-up was 18.8 months.

PD-1 inhibitors show strong efficacy and acceptable safety in periocular and orbital cSCC, offering a potential globe-sparing alternative to exenteration. Further studies are needed to refine treatment selection and timing.