June 03, 2025 | New Delhi, India- On June 12, 2025, the Food and Drug Administration approved pembrolizumab (Keytruda, Merck) for adults with resectable locally advanced head and neck squamous cell carcinoma (HNSCC) whose tumors express PD-L1 as determined by an FDA-approved test, as a single agent as neoadjuvant treatment, continued as adjuvant treatment in combination with radiotherapy (RT) with or without cisplatin after surgery, and then as a single agent.
This is the first approval for HNSCC in 6 years and the first overall perioperative approval for locally advanced HNSCC.
Perioperative Use: Three-Phase Immunotherapy Plan
The FDA based its decision on results from the KEYNOTE-689 trial, a Phase 3, randomized, multicenter study involving 714 patients with Stage III–IVA HNSCC. The approved treatment plan includes:
- Neoadjuvant phase: Pembrolizumab monotherapy, given every 21 days for two cycles before surgery.
- Adjuvant concurrent phase: 3 cycles of pembrolizumab with radiotherapy (± cisplatin).
- Maintenance phase: Pembrolizumab alone for 12 additional cycles following radiotherapy.
This treatment paradigm is focused on decreasing the risk of recurrence by stimulating the immune response early in the treatment and maintaining it after surgical resection.
Recommended Dosage
The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks. Pembrolizumab should be administered before chemotherapy when given on the same day.
Conclusion: Shifting the Standard of Care
With this approval, pembrolizumab becomes part of a new treatment paradigm for resectable head and neck cancer. Its integration into both pre- and post-surgical care provides a clinically meaningful survival benefit and could reshape the future of care for patients with locally advanced HNSCC.
