Cemiplimab for Locally Advanced and Metastatic Cutaneous Squamous-Cell Carcinomas: Real-Life Experience from the French CAREPI Study Group

SIMPLE SUMMARY: Prognosis of advanced cutaneous squamous-cell carcinoma (CSCC) is poor. Recent clinical trials have shown that immunotherapy achieves significantly improved survival of patients with advanced CSCCs. However, few real-world data are available on treatment patterns and clinical outcomes of patients with advanced CSCCs receiving anti-programmed cell-death protein-1 (PD-1). To approach this issue, we conducted a retrospective study on 245 patients with advanced CSCCs from 58 centers who had been enrolled in an early-access program; 240 received cemiplimab. Our objectives were to evaluate, in the real-life setting, best overall response rate, progression-free survival, overall survival and safety. Results demonstrated cemiplimab efficacy in patients with advanced CSCCs, regardless of immune status. Patients with good Eastern Cooperative Oncology Group performance status benefited more from cemiplimab. The safety profile was acceptable. ABSTRACT: Although cemiplimab has been approved for locally advanced (la) and metastatic (m) cutaneous squamous-cell carcinomas (CSCCs), its real-life value has not yet been demonstrated. An early-access program enrolled patients with la/mCSCCs to receive cemiplimab. Endpoints were best overall response rate (BOR), progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. The 245 patients (mean age 77 years, 73% male, 49% prior systemic treatment, 24% immunocompromised, 27% Eastern Cooperative Oncology Group performance status (PS) ≥ 2) had laCSCCs (35%) or mCSCCs (65%). For the 240 recipients of ≥1 infusion(s), the BOR was 50.4% (complete, 21%; partial, 29%). With median follow-up at 12.6 months, median PFS was 7.9 months, and median OS and DOR were not reached. One-year OS was 73% versus 36%, respectively, for patients with PS < 2 versus ≥ 2. Multivariate analysis retained PS ≥ 2 as being associated during the first 6 months with PFS and OS. Head-and-neck location was associated with longer PFS. Immune status had no impact. Severe treatment-related adverse events occurred in 9% of the patients, including one death from toxic epidermal necrolysis. Cemiplimab real-life safety and efficacy support its use for la/mCSCCs. Patients with PS ≥ 2 benefited less from cemiplimab, but it might represent an option for immunocompromised patients.