Effectiveness and safety of cemiplimab in locally advanced and metastatic cutaneous squamous cell carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer with increasing incidence. The anti-PD-1 therapy cemiplimab has shown its antitumor activity in locally advanced (lacSCC) and metastatic cSCC (mcSCC). This retrospective study assessed the real-life effectiveness and safety of cemiplimab in 83 patients with lacSCC (n = 53) and mcSCC (n = 30). The objective response rate (ORR) was 49.4%, with a complete response (CR) in 15.7% and a partial response (PR) in 33.7%. The median progression-free survival (PFS) was 14 months (95% CI 9-55) and the median overall survival (OS) 19 months (95% CI 10-39). Half of patients (50.6%) experienced adverse events (AE) of any grade, with 8.4% discontinuing therapy due to the severe AEs. The subset of patients who experienced progression during therapy displayed younger age (p = 0.002), a higher disease stage at baseline (p = 0.003), and a nodal disease (p = 0.041). No differences in survival outcome emerged between patients with nodal vs. distant metastases, previous radiotherapy recipient vs. radiotherapy-naïve, and immunosuppressed vs. immunocompetent patients. Head&neck tumor site was associated with a longer OS after first progression (OS2, HR 0.29, 95% CI 0.09-0.89). This study supports the safe and effective use of cemiplimab in real life clinical practice yet highlights the need for further identification of new predictors of clinical response.