Abstract Purpose: Neoadjuvant PD-1 blockade has shown marked efficacy before surgery in patients with head and neck cutaneous squamous cell cancer (CSCC). However, the potential for PD-1 blockade as a definitive, non-operative therapy remains uncertain. Patients and Methods: We conducted a single-institution retrospective study(2018–2023)of patients with locally advanced resectable stage III/IV CSCC treated with cemiplimab. Patients received neoadjuvant cemiplimab followed by surgery or cemiplimab monotherapy without surgery. The primary endpoint was objective radiological (assessed using iRECIST)and clinical response rate; secondary endpoints included disease-specific survival (DSS),progression-free probability(PFP),histopathologic response, and exploratory genomic biomarkers. Results: Fifty-one patients received cemiplimab monotherapy alone (median age;78.8 years) and 21 received neoadjuvant cemiplimab followed by surgery (median age;73 years). The 2-year DSS and PFP for cemiplimab monotherapy were 90% (95% CI, 80–100%) and 82% (95% CI, 72–94%), respectively. The 2-year DSS and PFP for neoadjuvant cemiplimab with surgery were 95% (95% CI, 86–100%) and 78% (95% CI, 62–100%), respectively. Tumor-infiltrating lymphocytes (TILs) were higher in patients with complete or partial response than in patients with progressive or stable disease (p=0.005, q=0.026), with absent TILs more frequent in non-responders. Tumor mutational burden was greater in complete (55.7) and partial (14.9) response than in progressive disease (4.9; p=0.02, q=0.04). Conclusions: n this retrospective, non-randomized cohort, definitive-intent cemiplimab monotherapy was associated with durable disease control in selected patients with locally advanced resectable head and neck CSCC. This study provides a promising real-world organ preservation experience for patients with advanced head and neck CSCC treated with cemiplimab monotherapy that does not compromise oncologic outcomes.
Kavanagh et al. (2026) studied this question.