FDA Grants Approval for Pembrolizumab in Treating Resectable Head and Neck Cancer

The U.S. Food and Drug Administration (FDA) has authorized the use of pembrolizumab, an immune checkpoint inhibitor, for the treatment of patients diagnosed with resectable locally advanced head and neck squamous cell carcinoma that exhibits PD-L1 expression, as established by an FDA-approved test.

This decision was informed by results from the KEYNOTE-689 clinical trial, a phase 3 study that was randomized and open-label. In this study, participants who received pembrolizumab both before and after standard surgical procedures demonstrated improved event-free survival rates as well as higher instances of significant tumor reduction prior to surgery. The research was conducted by a team from Dana-Farber Brigham Cancer Center and Washington University School of Medicine in St. Louis.

This new treatment approach signifies a pivotal shift in the management of head and neck cancer, allowing patients the opportunity to undergo pembrolizumab therapy before surgical intervention.

Dr. Ravindra Uppaluri, who spearheaded the study and serves as the director of Head and Neck Surgical Oncology at Dana-Farber, noted the significance of this advancement, marking it as the first substantial progress in this area in over twenty years.

Dr. Robert Haddad, chief of the Division of Head and Neck Oncology at Dana-Farber, emphasized that this approval represents the inaugural acceptance of a checkpoint inhibitor within the curative perioperative phase, indicating a major transformation in the treatment paradigm for surgically managed head and neck cancer.

The KEYNOTE-689 trial involved 714 newly diagnosed patients with stage 3 or stage 4A head and neck squamous cell carcinoma, who were randomly assigned to receive either pembrolizumab in conjunction with standard care or standard care alone. The study also involved assessing the PD-L1 levels in tumors to determine the influence of these levels on treatment effectiveness.

Results from the trial showed that patients treated with pembrolizumab enjoyed significantly longer event-free survival, with median event-free survival rates recorded at 51.8 months compared to 30.4 months for those who did not receive the drug, based on a median follow-up of 38.3 months. Additionally, there was a notable increase in the rate of major pathological responses, indicating effective immune-mediated tumor destruction observed in surgical samples.

The treatment was deemed safe, with no new side effects reported. Furthermore, patients who received pembrolizumab experienced timely surgical interventions without delays that could be attributed to side effects related to immunotherapy.

The findings from this study were previously shared at the 2025 American Association of Cancer Research (AACR) Annual Meeting.