The FDA approved pembrolizumab for patients with resectable locally advanced head and neck squamous cell carcinoma expressing PD-L1 (CPS ≥1), based on the pivotal KEYNOTE-689 phase 3 trial. Patients receiving pembrolizumab perioperatively had longer event-free survival and greater tumor shrinkage prior to surgery. This marks the first checkpoint inhibitor approval in the curative perioperative setting, representing a paradigm shift in head and neck cancer management. The trial was led by Dana-Farber and Washington University investigators.