Definitive Cemiplimab Shows Potential for Organ Preservation in Patients With Resectable Head and Neck Cutaneous Squamous Cell Carcinoma

Clinical Summary:

• Design/Population: This single-center trial evaluated patients with locally advanced, resectable stage III/IV head and neck cutaneous squamous cell carcinoma treated with cemiplimab monotherapy without surgery or neoadjuvant cemiplimab followed by surgery. 
• Key Outcomes: Definitive cemiplimab monotherapy was associated with durable disease control, with 2-year disease-specific survival and progression-free probability comparable to outcomes observed with neoadjuvant cemiplimab followed by surgery. Higher tumor-infiltrating lymphocytes and tumor mutational burden were associated with treatment response.
• Clinical Relevance: These findings support further investigation of definitive PD-1 blockade as a potential organ-preserving option for selected patients, although the retrospective, nonrandomized design limits direct comparisons with surgery-based treatment. 

Results from a retrospective trial demonstrated that definitive-intent cemiplimab monotherapy was associated with durable disease control in selected patients with locally advanced, resectable head and neck cutaneous squamous cell carcinoma (cSCC), suggesting a potential nonoperative approach for patients who respond to PD-1 blockade.

“Neoadjuvant PD-1 blockade has shown marked efficacy before surgery in patients with head and neck cSCC,” stated Fergal Kavanagh, MD, Memorial Sloan Kettering Cancer Center, New York, New York, and coauthors. “However, the potential for PD-1 blockade as a definitive, nonoperative therapy remains uncertain.”

In this single-center trial, researchers collected data from 72 patients with stage III/IV head and neck cSCC who received either cemiplimab monotherapy without surgery (n = 51) or neoadjuvant cemiplimab followed by surgical resection (n = 21) between 2018 and 2023. Primary end points were objective radiologic response, as assessed via immune Response Evaluation Criteria in Solid Tumors, and clinical response. Key secondary end points included disease-specific survival, progression-free probability, histopathologic response, and exploratory genomic biomarkers.

At analysis, the 2-year disease-specific survival rate was 90% in the cemiplimab monotherapy arm and 95% in the neoadjuvant cemiplimab arm. The 2-year progression-free probability rates were 82% and 78%, respectively. 

Exploratory biomarker analyses identified associations between the tumor immune microenvironment and response to cemiplimab. Tumor-infiltrating lymphocyte levels were significantly higher among patients who achieved a complete or partial response compared with patients who experienced stable or progressive disease (P = .005). Absent tumor-infiltrating lymphocytes were also more frequently observed among nonresponders. 

Tumor mutational burden was also associated with response. Tumor mutational burden was higher among patients who achieved a complete or partial responses than among those with progressive disease (P = .02).

“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,” concluded Dr Kavanagh et al. “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.”

Source:

Kavanagh FG, Instrum RS, Boe LA, et al. Nonoperative management of locally advanced resectable cutaneous squamous cell cancer of the head and neck with PD-1 blockade. Clin Cancer Res. Published online: September 1, 2026. doi: 10.1158/1078-0432.ccr-26-0123