Nonoperative Management of Locally Advanced Resectable Cutaneous Squamous Cell Cancer of the Head and Neck with PD-1 Blockade.

PURPOSE: Neoadjuvant PD-1 blockade has shown marked efficacy before surgery in patients with head and neck cutaneous squamous cell cancinoma (CSCC). However, the potential for PD-1 blockade as a definitive, nonoperative therapy remains uncertain.

EXPERIMENTAL

DESIGN

We conducted a single-institution retrospective study (2018 to 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 the objective radiologic response rate (assessed using immune Response Evaluation Criteria in Solid Tumors) and clinical response rate; the 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% confidence interval (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 (TIL) were higher in patients with complete response (CR) or partial response (PR) than in patients with progressive disease (PD) or stable disease (P = 0.005, q = 0.026), with absent TILs more frequent in nonresponders. Tumor mutational burden was higher in CR (55.7) and PR (14.9) than in PD (4.9; P = 0.02, q = 0.04).

CONCLUSIONS

In this retrospective, nonrandomized 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.