RAHWAY, N.J. — The U.S. Food and Drug Administration has approved Merck’s Keytruda (pembrolizumab) for a new use in adults with resectable locally advanced head and neck squamous cell carcinoma (HNSCC) whose tumors express PD-L1 (CPS ≥1). The approval marks the first FDA-sanctioned perioperative anti-PD-1 treatment regimen for this patient group, allowing the immunotherapy to be used both before and after surgery in combination with radiotherapy, with or without cisplatin, and then continued as a single agent.
The decision is based on data from the Phase 3 KEYNOTE-689 trial, which demonstrated that Keytruda significantly reduced the risk of disease progression, recurrence, or death by 30% compared to the current standard of care. Patients whose tumors expressed PD-L1 and received the Keytruda-based regimen had a median event-free survival (EFS) of nearly 60 months, compared to just under 30 months in the control group.
“This approval represents a potentially significant shift in how we manage this disease,” said Dr. Ravindra Uppaluri, principal investigator of the study and director of Head and Neck Surgical Oncology at Brigham and Women’s Hospital and Dana-Farber Cancer Institute. “Offering Keytruda before and after surgery provides a new path forward for improving long-term outcomes.”
The approval also underscores Merck’s continuing expansion of Keytruda’s indications in oncology. Already approved for use in advanced and recurrent HNSCC, Keytruda’s latest label includes use as a neoadjuvant and adjuvant therapy in combination with radiation—with or without cisplatin—and as monotherapy post-treatment in appropriate patients.
“This new treatment regimen has the potential to shift the treatment paradigm,” said Dr. Marjorie Green, senior vice president and head of oncology at Merck Research Laboratories. “These results reinforce Keytruda’s ability to improve outcomes in a challenging cancer while potentially reducing the need for aggressive long-term treatments.”
The KEYNOTE-689 trial enrolled 714 patients with resectable Stage III–IVA HNSCC, randomly assigning them to receive either the perioperative Keytruda regimen or standard post-surgical care with radiation and, when indicated, cisplatin. Keytruda was administered before surgery, continued after surgery with radiation (with or without cisplatin), and then as a single agent for up to a year. The trial was conducted globally and evaluated event-free survival as its primary outcome.
Keytruda was generally well tolerated, though as with other immunotherapies, it was associated with a range of potential immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, and severe infusion-related reactions. In the neoadjuvant phase, 11% of patients experienced serious adverse events, and in the adjuvant phase, 38% of patients did.
The FDA’s decision was reviewed under Project Orbis, a regulatory collaboration initiative that allows simultaneous review of oncology products across multiple countries. Applications based on KEYNOTE-689 are currently under review in several countries, including Canada, Australia, Brazil, and the European Union.
Keytruda remains a cornerstone of Merck’s oncology portfolio and is already approved for several indications in HNSCC, including use in metastatic or unresectable cases. This new approval further cements its role as a foundational immunotherapy for head and neck cancer treatment.
