The FDA has approved pembrolizumab for patients with resectable locally advanced head and neck squamous cell carcinoma expressing PD-L1, marking the first checkpoint inhibitor approval in the curative perioperative setting. This decision, underpinned by the pivotal KEYNOTE-689 phase 3 study led by Dana-Farber and Washington University School of Medicine, demonstrated extended event-free survival and meaningful tumor shrinkage. Experts from Dana-Farber highlight this as a major advance and a workflow-shifting treatment option for appropriate patients.