On June 12, 2025, the FDA approved pembrolizumab (Keytruda) as a new treatment option for adults with resectable, locally advanced head and neck squamous cell carcinoma (HNSCC) that shows PD-L1 expression with a combined positive score (CPS) of 1 or higher. This approval introduces a new approach to treating head and neck cancer that begins before surgery and continues afterward.
The treatment plan includes pembrolizumab alone before surgery (neoadjuvant therapy), followed by a combination of pembrolizumab and radiation therapy (with or without cisplatin) after surgery, and then pembrolizumab alone as maintenance therapy. This decision was based on results from the phase 3 KEYNOTE-689 trial (NCT03765918), which showed a clear benefit in event-free survival (EFS).
In the trial, patients who received pembrolizumab had a median EFS of 51.8 months compared to 30.4 months for those who received the standard of care (SOC). The results also showed significant tumor shrinkage and pathological responses in both primary tumors and lymph nodes before surgery.
Dr. Ravindra Uppaluri, MD, PhD, from Dana-Farber Brigham Cancer Center, highlighted that the current SOC has been in place for over 20 years and has often led to limited results and high toxicity. The KEYNOTE-689 data marks a major improvement and brings hope to both patients and providers. Although overall survival data is still being collected, the strong EFS results suggest better long-term outcomes.
In terms of safety, the use of pembrolizumab was generally well tolerated, with side effects consistent with what has been seen in previous studies. No new safety concerns were identified.
This FDA approval not only changes the standard of care for patients with locally advanced HNSCC but also encourages future research into using similar immunotherapy approaches in other cancers. The success of this trial reinforces the need for strong teamwork among surgeons, oncologists, and other specialists to deliver the best care.
