Immune checkpoint inhibitors with or without chemotherapy for orbital, conjunctival, and ocular adnexal squamous cell carcinoma.

Objective: Periocular squamous cell carcinoma (SCC) is relatively rare and presents unique anatomic considerations due to proximity to the eye and risk to ocular structures associated with high-dose radiation therapy or radical surgery. We present our observations in patients with periocular SCC treated with immune checkpoint inhibitor (ICI) therapy in an effort to decrease surgical morbidity or avoid high-dose radiation therapy.

Methods: Retrospective review of patients with orbital, conjunctival, or periocular SCC who were treated with ICI either in the neoadjuvant setting prior to surgery or for treatment of perineural spread in the orbit/skull base.

Results: Twelve men and 5 women with orbital (n = 6), conjunctival (n = 5), or lacrimal sac/duct (n = 2) SCC, or SCC with perineural spread (n = 4) were treated with ICI (cemiplimab or pembolizumab) either as single drug (n = 9) or combined with chemotherapy (n = 8). Overall, 5 patients achieved complete response, 8 patients achieved partial response, and 4 patients achieved stable disease, using the response evaluation criteria in solid tumors (RECIST) criteria. The objective response rate was 76.5%. In 12 patients ICI was used in the neoadjuvant setting prior to surgery. In 4 patients with perineural spread and unresectable disease, ICI was used to avoid high-dose radiation therapy. One additional patient with conjunctival SCC with nodal metastasis was treated with ICI alone and achieved a dramatic complete response and has thus far managed to avoid surgery altogether.

Conclusions: ICI either as single drug or in combination with chemotherapy has a high response rate in patients with periocular SCC. Future prospective trials should aim to correlate molecular data with response.