FDA Approves Pembrolizumab for Resectable Head and Neck Cancer with PD-L1 Expression

The U.S. Food and Drug Administration (FDA) has granted approval for pembrolizumab, an immune checkpoint inhibitor, to treat patients with resectable, locally advanced head and neck squamous cell carcinoma exhibiting PD-L1 expression (Combined Positive Score, CPS, ≥1), as confirmed by an FDA-approved test. This approval is based on compelling results from the KEYNOTE-689 phase 3 trial, which demonstrated significant benefits for patients receiving pembrolizumab in the perioperative setting.

The study involved 714 newly diagnosed stage 3 and 4A head and neck cancer patients, who were randomized to receive pembrolizumab before surgery (neoadjuvant), during, and after (adjuvant) standard treatment, or to undergo standard treatment alone. Results showed that patients treated with pembrolizumab experienced a median event-free survival of 51.8 months compared to 30.4 months in the control group, with follow-up averaging 38.3 months. Additionally, the treatment led to higher rates of major pathologic response, indicating substantial tumor destruction mediated by immune response.

Safety profiles remained acceptable, with no new side effects reported, and patients experienced timely surgeries without delays caused by immunotherapy-related complications. The trial's findings were presented at the 2025 AACR Annual Meeting and underscore a paradigm shift in managing surgically treated head and neck cancers.

Experts highlight that this approval marks the first time a checkpoint inhibitor has been approved in the perioperative (pre- and post-surgery) setting for this cancer type, opening new avenues for improving outcomes. Dr. Ravindra Uppaluri, the study’s principal investigator, emphasized the relevance of this breakthrough, describing it as the first significant advancement in classic head and neck cancer treatment in over two decades. Dr. Robert Haddad, a leading oncologist, remarked that this development signifies a major change in treatment workflows, benefitting patients with advanced disease.