Survival for head and neck squamous cell carcinoma treated with versus without neoadjuvant systemic therapy: A national propensity score–matched analysis.

6035 Background: Neoadjuvant systemic therapies, including immunotherapy and chemotherapy, offer a promising approach for treating head and neck squamous cell carcinoma (HNSCC). These therapies aim to reduce tumor burden and enable personalized treatment. While pivotal studies like KEYNOTE 689 may redefine therapeutic paradigms, the survival outcomes associated with neoadjuvant systemic therapies in HNSCC remain underexplored. Methods: A retrospective cohort analysis using the National Cancer Database evaluated patients with HNSCC surgically treated with versus without neoadjuvant systemic therapies from 2015 to 2022. Overall survival (OS) was compared by using a Cox proportional hazards regression model. Propensity score matching was performed to adjust for stage, age, sex, race, insurance status, urban/rural, Charlson–Deyo score. Results: Among 3,569 patients (74% male, 26% female), 1,311 received neoadjuvant chemotherapy, 632 received neoadjuvant immunotherapy, 114 received a combination of neoadjuvant chemotherapy and immunotherapy, and 1,512 were matched HNSCC patients who did not receive any neoadjuvant therapy prior to surgery. Most patients had overall stage IVa/b (59%) tumors of the oral cavity (62%). On univariate analysis, neoadjuvant immunotherapy alone was associated with a 43% reduced the risk of mortality, compared to neoadjuvant chemotherapy alone (HR: 0.57; 95% CI: 0.48–0.68, P < .001 ). Combination therapy was not significantly associated with lower mortality than chemotherapy alone (HR: 0.87; 95% CI: 0.63–1.21, P = .41 ). After adjustment using a propensity matched cohort of patients with HNSCC treated without neoadjuvant therapy, neoadjuvant immunotherapy was associated with significantly improved OS (HR: 0.55; 95% CI: 0.35-0.75, P < .001 ). However, neoadjuvant chemotherapy (HR: 1.07; 95% CI: 0.96–1.18, P = .23 ) and combination therapy (HR: 0.84; 95% CI: 0.49-1.19, P = .33 ) were not significantly associated with improved OS. Conclusions: Neoadjuvant immunotherapy may potentially provide improved survival in HNSCC. Further research is needed to assess these findings through prospective trials. Overall survival for patients with head and neck squamous cell carcinoma treated with versus without neoadjuvant systemic therapy. Overall Survival HR (95% CI) P No neoadjuvant therapy Ref. Neoadjuvant chemotherapy 1.07 (0.96–1.18) 0.23 Neoadjuvant combination therapy 0.84 (0.49-1.19) 0.33 Neoadjuvant immunotherapy 0.55 (0.35-0.75) <0.001 HR, hazard ratio; CI, confidence interval.