Second-line treatments for patients with PD1-refractory cutaneous squamous cell carcinomas: a brief report

Abstract Background Patients with locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC), who failed cemiplimab, have a poor prognosis, with most patients dying of disease. Second-line therapies consist of additional immunotherapy, epidermal growth factor receptor (EGFR) inhibitors, chemotherapy, salvage surgery, or radiotherapy. Outcomes in this setting remain poorly characterized. We review the first two options for our population. The study objective was to describe non-clinical-trial/off-label immunotherapy treatments for advanced, recurrent, or refractory cSCC. Patients and Methods This single-institution retrospective case series took place at The Ohio State University Comprehensive Cancer Center, a high-volume academic medical oncology practice. Methods We reviewed the electronic medical records of patients who underwent systemic treatments for advanced cSCC. Patient demographics, clinicopathologic history, cancer data, treatments, and outcomes were abstracted. Overall response and progression-free survival by clinical judgment and overall survival rates were described. Results A total of 21 patients were included. Thirteen received cetuximab and 12 ipilimumab after failure of surgery and/or radiation, and of a programmed cell death protein 1 (PD-1) monoclonal inhibitor (primarily cemiplimab). Four patients are included in both cohorts. Durable complete responses were observed only in patients treated with ipilimumab. Otherwise, all other surviving patients had salvage surgery after some response to second line therapy. Conclusion In this salvage setting, ipilimumab demonstrated a 33% response rate, including complete responses with durable survival. Cetuximab induced response in patients pretreated with cemiplimab whether they had responded or not to this immunotherapy. Most cetuximab-treated patients died within 1-2 years, unless salvaged with surgery.