Immunotherapy Utilization Outcomes in Distantly Metastatic Head and Neck Squamous Cell Carcinoma

Importance: Immunotherapy is part of multimodal treatment for distantly metastatic head and neck squamous cell carcinoma (mHNSCC); however, survival outcomes outside of clinical trials have not been systematically assessed. This study used the US National Cancer Database (NCDB) to evaluate the use and outcomes of nonpalliative immunotherapy across various HNSCC primary sites outside of clinical trial settings. Objective: To assess the routine clinical use of nonpalliative immunotherapy and its survival outcomes for different primary sites of mHNSCC. Design, Setting, and Participants: This was a large population-based cohort study using data from the NCDB, a cancer registry of patients treated at more than 1500 hospitals in the US. Eligible participants were patients with mHNSCC who received immunotherapy from 2013 to 2020. Data analysis was conducted from October 2023 and March 2025. Exposure: Receiving immunotherapy or not. Main Outcomes and Measures: Overall survival (OS) following mHNSCC diagnosis was the primary outcome. The secondary outcome was prognostic factors of OS stratified by primary site. Kaplan-Meier and multivariable Cox regression models were used in the analysis. Results: Among 5059 patients with mHNSCC (mean [SD] age at diagnosis, 64.6 [10.6] years; 4074 male [80.5%]; 162 Asian [3.2%], 763 Black [15.1%], 267 Hispanic [5.3%], 19 Native American [0.4%], and 3848 White [76.1%] individuals), there were 1073 (21.3%) who received immunotherapy and 3986 (78.8%) who did not. Immunotherapy use increased year over year from 2013 to 2020 (9.3% vs 33.8%). Immunotherapy recipients were predominantly covered by Medicare (539 patients [22.3%]) or privately insured (310 patients [23.9%]). Patients receiving both chemotherapy and immunotherapy had the longest median survival at 19.1 (95% CI, 17.0-21.5) months, followed by those receiving chemotherapy alone at 17.3 (95% CI, 16.6-18.3) months. Compared to chemotherapy alone, multivariable Cox analysis demonstrated improved OS for the addition of immunotherapy (hazard ratio [HR], 0.81; 95% CI, 0.72-0.91) but worse OS for immunotherapy alone (HR, 1.25; 95% CI, 1.08-1.45) and no chemotherapy or immunotherapy (HR, 2.31; 95% CI, 2.12-2.52). Adding immunotherapy to chemotherapy improved OS in patients with hypopharyngeal (HR, 0.66; 95% CI, 0.50-0.86), oral cavity (HR, 0.76; 95% CI, 0.59-0.98), and laryngeal (HR, 0.81; 95% CI, 0.66-1.00) cancers, but not for p16-positive (HR, 1.05; 95% CI, 0.79-1.39) or p16-negative (HR, 1.33; 95% CI, 0.96-1.86) oropharyngeal cancers. Conclusions and Relevance: This cohort study found that immunotherapy use increased significantly from 2013 to 2020 for mHNSCC treatment, particularly at academic centers. Immunotherapy use was associated with modest OS improvement in patients with hypopharyngeal, oral cavity, and laryngeal cancers, but not for those with oropharyngeal cancer.