In patients with high-risk cSCC, recurrence remains a major concern despite curative-intent surgery. A recent phase 3 trial offers compelling evidence supporting systemic adjuvant therapy in this setting. The study enrolled 415 individuals with resected local or regional cSCC harboring aggressive features—including extracapsular extension, extensive nodal disease, T4 tumors with bone involvement, perineural invasion, or recurrence. Participants were randomized to receive either cemiplimab or placebo.

Cemiplimab dosing began with 350 mg IV every 3 weeks for 12 weeks, escalating to 700 mg every 6 weeks for a total of up to 48 weeks. At a median follow-up of 24 months, the treatment group showed a striking improvement in disease-free survival (DFS), with a hazard ratio of 0.32 and a 24-month DFS rate of 87.1%, compared to 64.1% with placebo (P<0.001). Cemiplimab also reduced the risk of both locoregional and distant recurrence significantly.

However, this benefit came with a higher incidence of grade 3 or greater adverse events (23.9% vs. 14.2%) and a greater rate of treatment discontinuation (9.8% vs. 1.5%). Despite these risks, the findings position adjuvant cemiplimab as a promising therapeutic strategy to improve outcomes in this high-risk patient group.

"These results indicate that adjuvant cemiplimab significantly extends disease-free survival and reduces recurrence in high-risk cSCC patients, supporting its role as a beneficial adjuvant therapy in this population," write the authors.

DRUG AT A GLANCE: Cemiplimab 

Cemiplimab is a fully human monoclonal antibody that targets the PD-1 receptor, enhancing T-cell–mediated immune responses against tumors. It is FDA-approved for advanced cutaneous squamous-cell carcinoma (cSCC), basal cell carcinoma, and non-small cell lung cancer, and is administered via intravenous infusion.