Immune Checkpoint Inhibitor Therapy as a Novel and Effective Therapy for Aggressive Cutaneous Squamous-cell Carcinoma

Background: Patients with metastatic or locally aggressive cutaneous squamous-cell carcinoma (cSCC) have historically had limited and noneffective treatment options. The mainstay treatment has been surgery, which can be disfiguring and may not be technically feasible for larger lesions. Patients and Methods: A retrospective review of 18 patients treated with nivolumab (n = 17) or pembrolizumab (n = 1) anti-programmed cell death protein 1 (PD-1) inhibitors for metastatic or locally advanced cSCC from March 2015 to present was performed. Results: Three patients had metastatic disease, 5 patients had locally aggressive plus regional nodal disease, 8 patients had locally advanced disease, and 2 had multifocal skin disease. Seventeen patients had undergone at least 1 surgery, 12 also had received radiotherapy, 8 had disease that had failed to respond to other systemic treatments, and 2 had chronic lymphocytic leukemia. Of 18 patients treated, 14 had dramatic responses with improvement in clinical symptoms and impressive tumor reduction with equally impressive duration. Objectively, 4 patients had complete response, 10 had partial response, 3 had stable disease, and 1 patient had progression of disease. Three patients died, 1 from an ischemic cerebrovascular incident possibly related to treatment, 1 likely not related to neither treatment nor disease, and 1 due to disease progression. Therapy was otherwise well tolerated, and 10 patients currently continue to receive the therapy. Thirteen patients continue to have stable or no new disease at a median time of 12 months since the start of treatment. Conclusion: PD-1 blocking agents may provide clinically meaningful and palliative therapy for patients with aggressive cSCC who are not surgical candidates.