Pembrolizumab sets new standard in advanced head and neck cancer surgery, trial shows

Editor's Note

According to results from a randomized trial, titled KEYNOTE-689, adding pembrolizumab (Keytruda) to surgery and standard adjuvant therapy significantly prolongs event-free survival (EFS) in patients with resectable, locally advanced head and neck squamous cell carcinoma (HNSCC), MedPage Today April 28 reports. Experts are calling the findings a major advance—and a new standard of care—for this high-risk patient population.

The randomized Phase III trial included 714 previously untreated patients with resectable HNSCC. Participants who received two cycles of neoadjuvant pembrolizumab, followed by surgery and adjuvant pembrolizumab in combination with standard chemoradiotherapy or radiotherapy, achieved a median EFS of 51.8 months compared to 30.4 months for those who received standard therapy alone. The benefit was most pronounced in tumors expressing PD-L1. For patients with a combined positive score (CPS) ≥10, median EFS reached nearly 60 months versus 26.9 months with standard treatment alone.

Although overall survival has not yet reached statistical significance, interim data show a positive trend, especially in the CPS ≥10 population. Robert Ferris, MD, PhD, of UNC Lineberger, hailed the trial as a long-awaited breakthrough, emphasizing that toxicity remained manageable, noted the article. He pointed to previous failures of perioperative immunotherapy trials in this space and emphasized that KEYNOTE-689 demonstrates how immunotherapy can be integrated safely and effectively in early-stage disease to maximize long-term impact.

Patients in the pembrolizumab group were stratified into high- and low-risk groups post-surgery. High-risk patients received pembrolizumab with chemoradiation; low-risk patients received pembrolizumab with radiotherapy alone. The control group received the same postoperative therapies without pembrolizumab. Dr Ferris concluded that pembrolizumab in the perioperative setting not only extends survival but does so with an acceptable safety profile, setting the stage for wider application in early-stage and operable HNSCC.