The phase 3 KEYNOTE-048 trial compares pembrolizumab with or without concurrent chemotherapy to cetuximab-chemotherapy in patients with recurrent or metastatic head and neck SCC. Patients were evaluated in subgroups based on PD-L1 expression. In median survival, pembrolizumab + chemotherapy outperformed cetuximab + chemotherapy in all patient subgroups regardless of PD-L1 expression. In the PD-L1 CPS 1-19 subgroup, pembrolizumab alone slightly outperformed cetuximab + chemotherapy. In the PD-L1 CPS < 1 subgroup median survival was significantly lower with pembrolizumab alone.