Burtness et al. recently published the landmark Keynote-48 study, demonstrating a survival benefit for pembrolizumab monotherapy and pembrolizumab/chemotherapy, compared with cetuximab/chemotherapy, in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). These data are impactful and practice-changing, and have rapidly been adopted in practice, with increasing numbers of HNSCC patients receiving either pembrolizumab monotherapy, or pembrolizumab / chemotherapy, in the first line recurrent / metastatic setting. Pembrolizumab was approved as a single agent for patients whose tumors express PD□L1 (Combined Positive Score [CPS] ≥1), while pembrolizumab / chemotherapy was approved for use in the United States for all patients irrespective of PD-L1 expression.