Immune checkpoint inhibitor therapy for treatment of periocular Merkel cell carcinoma: A systematic review of clinical outcomes and safety

Clinical Snapshot

Key Findings

• P Value: Not applicable (descriptive analysis)

• Effect Size: 90% complete response rate

• Primary Outcome: Complete response rate: 90% (9/10 patients)

• Nnt Or Sensitivity: Number needed to treat: approximately 1.1 for complete response

• Confidence Interval: Not reported

Clinical Application

Limited by drug availability, cost, and need for specialized oncology care; requires multidisciplinary approach Pembrolizumab and avelumab available through PBS for advanced MCC; would require specialist consultation and likely compassionate use protocols for periocular cases Patients with periocular Merkel cell carcinoma, both localized and metastatic disease

Abstract

Merkel cell carcinoma (MCC) is a rare, aggressive neurocutaneous malignancy associated with ultraviolet damage, immunosuppression, and Merkel cell polyoma virus infection. Periocular MCC is uncommon but has high rates of local recurrence and metastasis and presents unique therapeutic challenges due to functional and cosmetic considerations. Immune checkpoint inhibitor (ICI) therapy has shown efficacy in systemic MCC; however, evidence for periocular use is limited to small case series and reports without consolidated evidence or consensus. Thus, this study summarizes and evaluates the effectiveness and safety of ICIs for periocular MCC. A systematic literature search across PubMed, Embase, and Web of Science was conducted according to PRISMA guidelines. Randomized and nonrandomized studies, case series, and case reports in English describing ICI use for periocular MCC were included. Non-human studies, non-periocular MCC, and reports without ICI treatment were excluded. Extracted data included patient demographics, tumor characteristics, treatment regimen, and patient outcomes. Seven studies reporting ten patients were included. Treatment regimens consisted of pembrolizumab (n = 6) and avelumab (n = 3), or both medications (n = 1). At a mean follow-up of 11.4 ± 9.0 months, nine patients had complete response (90%); only one patient developed subsequent distant progression despite local response. Patients with both localized periocular disease and metastatic involvement demonstrated favorable responses to ICI. Adverse effects were infrequent and typically mild; only one patient discontinued therapy due to adverse effects. ICIs may be an effective and well-tolerated treatment for local and advanced periocular MCC; however, larger, prospective studies are needed.

References

1. 1.Folk, G. A., Lee, W., & Shoji, M. K. (2026). Immune checkpoint inhibitor therapy for treatment of periocular Merkel cell carcinoma: A systematic review of clinical outcomes and safety. Indian Journal of Ophthalmology, 74(6), 1234-1241. https://doi.org/10.4103/IJO.IJO_3208_25