Patterns of response to immune checkpoint inhibitors in association with genomic and clinical features in patients with Head and Neck Squamous Cell Carcinoma (HNSCC)

Immunotherapy agents, such as immune checkpoint inhibitors (ICIs), act through different mechanisms compared to conventional chemotherapy and are characterized by unique patterns of response, such as hyperprogression (HPD), which refers to the paradoxical acceleration of tumor growth kinetics (TGK). In this regard, we sought to compare patterns of response to ICIs with respect to clinical and genomic features in a cohort of patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). In our cohort, HPD was observed in 15.4% of patients. We report for the first time an association of HPD with both shorter progression free survival and overall survival in HNSCC. Importantly, in a multivariate Cox analysis, the presence of HPD remained an independent prognostic factor for survival. Primary site in the oral cavity and administration of ICI in the second/third setting were significant predictors of HPD in multivariate analysis. Comprehensive genomic profiling performed with OncoDEEP biomarker test revealed that gene amplification was more common in HPD patients.