Emerging immune checkpoint inhibitors for the treatment of head and neck cancers.

: The benefits of immune checkpoint inhibitors (ICIs) in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) have been demonstrated through multiple studies to improve overall survival (OS) with decreased side effects when compared to the standard of care (SOC) treatment regimens in place for decades, leading to the approval of two ICIs, nivolumab and pembrolizumab. There has been a subsequent influx in the development of novel immunotherapy agents for the treatment of HNSCC. : Data for anti-programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) and anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) antibodies in treatment of R/M HNSCC will be reviewed. Emerging immune checkpoint inhibitors as well as combined therapies in HNSCC will be discussed. The role of predictive biomarkers, HPV-status, PD-L1 expression, and challenges related to treating patients with ICIs will be summarized. : A shift toward ICIs as SOC for the treatment of R/M HNSCC will continue as emerging immune checkpoints and combination therapies are evaluated. Response rates are variable in this patient population underlying the importance of identifying predictive biomarkers to aid in patient selection for ICI treatment.