Comprehensive Genomic Profiling Reveals Clinical Associations in Response to Immune Therapy in Head and Neck Cancer

Simple Summary The response rate of head and neck cancer (HNC) to immune checkpoint inhibitors (ICIs) can be as low as 20%. Biomarkers need to be elucidated to predict therapeutic response. Comprehensive genomic profiling (CGP) provides information on cancer-related genetic aberrations. Among the 1100 HNC cases in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, only 5% received biomarker-matched therapy, including NTRK fusion. Cases of squamous cell carcinoma (SCC) with a high tumor mutational burden (TMB) (>= 10 Mut/Mb) showed long-term survival (>2 years) in response to ICI therapy. However, the cases with CCND1 amplification showed a significantly lower response to ICI therapy. Therefore, CCND1 amplification may serve as a negative prognostic marker. Therefore, CGP may be useful for establishing prognostic biomarkers for immunotherapy in patients with HNC. Comprehensive genomic profiling (CGP) provides information regarding cancer-related genetic aberrations. However, its clinical utility in recurrent/metastatic head and neck cancer (R/M HNC) remains unknown. Additionally, predictive biomarkers for immune checkpoint inhibitors (ICIs) should be fully elucidated because of their low response rate. Here, we analyzed the clinical utility of CGP and identified predictive biomarkers that respond to ICIs in R/M HNC. We evaluated over 1100 cases of HNC using the nationwide genetic clinical database established by the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) and 54 cases in an institution-based study. The C-CAT database revealed that 23% of the cases were candidates for clinical trials, and 5% received biomarker-matched therapy, including NTRK fusion. Our institution-based study showed that 9% of SCC cases and 25% of salivary gland cancer cases received targeted agents. In SCC cases, the tumor mutational burden (TMB) high (>= 10 Mut/Mb) group showed long-term survival (>2 years) in response to ICI therapy, whereas the PD-L1 combined positive score showed no significant difference in progression-free survival. In multivariate analysis, CCND1 amplification was associated with a lower response to ICIs. Our results indicate that CGP may be useful in identifying prognostic biomarkers for immunotherapy in patients with HNC.