Immune checkpoint inhibitors in advanced cutaneous squamous cell carcinoma: Real-world evidence

e21519 Background: Immune checkpoint inhibitors (ICI) Cemiplimab and Pembrolizumab have revolutionized the treatment of advanced cutaneous squamous cell carcinoma (cSCC). We aimed to evaluate efficacy and safety of ICI in a real-world cSCC population, including patients with conditions which would exclude trial participation. Methods: In this single-center retrospective cohort study, we included all non-trial patients with advanced cSCC treated with ICI between 2017 and 2022. We aimed to assess efficacy outcomes according to age, comorbidities, and immune-related adverse events (irAE). Best overall response (BOR) was investigator-assessed. X 2 , Fisher’s exact, and Mann-Whitney U tests were used to compare subgroups of interest, and Cox proportional hazards models were fitted. The log-rank test was used to assess progression free survival (PFS) and overall survival (OS). Results: We identified 35 patients. Characteristics are displayed in the table. Median follow-up was 21.8 months (95% CI 19.3-24.4). BOR to ICI was partial response (PR) in 42.9%, complete response (CR) in 28.6%, and stable disease in (SD) 14.3% of patients. Main reasons for discontinuation of treatment were progression of disease (PD) in 20%, achievement of maximum benefit in 17.1%, and toxicities in 14.3%. Treatment beyond progression was given to 22.9% patients. The PFS rate at 1 year was 62%; median PFS was not reached (NR). PFS and OS were similar between patients with or without comorbidities, ECOG performance status 0-1 versus 2-3, or between age groups ≥75 years versus <75. IrAE grade 1-2 and 3-4 were seen in 80% and 14.3% of patients, respectively. Patients with grade 1-2 irAE had greater PFS than those without toxicities (HR 0.16; 95%CI 0.045-0.567, p=0.005). The OS rate at 1 year was 76%, with a median OS of 38.57 months (95% CI 19.4-57.7). Responders (CR+PR) had a prolonged median OS compared to non-responders (SD+PD): 38.57 months versus 9 months (HR 0.083; 95%CI 0.17-0.406, p=0.002). Conclusions: ICI were effective and safe among real-world cSCC patients, independent of age, comorbidities or ECOG. Our BOR was higher than in the published clinical trials, which might reflect the subjective nature of investigator-assessed response or the small sample size assessed. [Table: see text]