The FDA has approved pembrolizumab for patients with resectable locally advanced head and neck squamous cell carcinoma expressing PD-L1, based on the phase 3 KEYNOTE-689 trial. The regimen of perioperative pembrolizumab with standard surgery improved event-free survival and tumor shrinkage, marking a paradigm shift in treatment. Dana-Farber Brigham Cancer Center led the pivotal study demonstrating this first checkpoint inhibitor approval in the curative perioperative setting.