Efficacy of Neoadjuvant Cemiplimab Treatment for Cutaneous Squamous Cell Carcinoma

Background/Objectives: Skin cancer is the most common cancer worldwide, primarily divided into melanoma and non-melanoma types, with non-melanoma being the most prevalent. Cutaneous squamous cell carcinoma (cSCC) represents 50% of primary skin cancers and is characterized by uncontrolled keratinocyte proliferation. cSCC current standard treatment is surgical resection and chemotherapy. Unfortunately these methods often lead to disfigurement, functional morbidly and compromised function. In contrast from immunotherapy emerging scenarios that have shown promising results, especially in neoadjuvant settings. Cemiplimab (Libtayo®; Regeneron, Tarrytown, New York, United States), a PD-1 monoclonal antibody, has shown efficacy in treating advanced or metastatic cSCC, and its use as a neoadjuvant therapy has been recently explored. This review aims to evaluate Cemiplimab neoadjuvant setting on cSCC treatment. Methods: Following PRISMA guidelines, this review analyzed studies on Cemiplimab as neoadjuvant therapy for cSCC, sourced from PubMed, Web of Science, and Scopus. Only controlled trials, cohort studies, case series, and systematic reviews were included. A total of 21 studies were examined, focusing on response rates, adverse effects, and outcomes. Results: From 341 records, 21 studies were included, and six clinical trials provided key data.The targeted data revealed that neoadjuvant Cemiplimab showed a mean pathologic response rate of 72%, with a 62% objective response rate. The most commonly found treatment-related adverse events (TRAEs) included fatigue, maculopapular rash, and diarrhea, affecting 66% of patients, with few severe cases. The studies demonstrated high rates of complete pathological responses (cPR) and major pathological responses (mPR), suggesting a strong therapeutic potential. Conclusions: Neoadjuvant Cemiplimab for cSCC therapy shows high response rates, low recurrence, improved survival, and manageable side effects. Despite more research is still needed to confirm its long-term benefits and real-world settings feasibility, some case series already indicate comparable results in immunosuppressed patients. Finally, there is strong evidence to consider neoadjuvant Cemiplimab as a promising and efficient treatment