Real-World Outcomes of Immune Checkpoint Inhibitors in Head and Neck Squamous Cell Carcinoma: Analyzing Patient-Specific Factors Influencing Survival and Response Rate.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a globally significant disease with poor survival outcomes. Immune checkpoint inhibitors (ICIs) such as pembrolizumab and nivolumab have improved treatment paradigms, yet their real-world efficacy and the factors influencing treatment outcomes remain underexplored. AIMS: This study aimed to evaluate real-world outcomes of pembrolizumab and nivolumab therapy in patients with HNSCC and to identify clinical and laboratory factors associated with overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). METHODS AND RESULTS: We conducted a retrospective analysis of 45 HNSCC patients treated with pembrolizumab or nivolumab at the University Medical Center Mannheim. Patient-specific factors, including tumor characteristics, PD-L1 expression, and laboratory parameters, were assessed using Kaplan-Meier estimation, log-rank tests, and multivariate regression models. The median OS and PFS were 10.4 months and 7.4 months, respectively, with an ORR of 22%. A tumor proportion score (TPS) ≥ 50% and absence of smoking or alcohol abuse significantly improved ORR, while female sex, high neutrophil-to-lymphocyte ratio (NLR), and elevated leukocyte counts were associated with inferior OS and PFS. Real-world outcomes largely aligned with the pivotal trials Keynote-048 and CheckMate 141. CONCLUSION: This study underscores the predictive value of TPS and patient lifestyle factors in ICI treatment for HNSCC. The findings also highlight sex-specific differences, as well as NLR and leukocyte count as potential prognostic factors. Larger, more diverse cohorts are needed to confirm these results and refine patient selection strategies.