Merck Keytruda approved by USFDA for Advanced Head and Neck Cancer

The approval is based on data from the pivotal Phase 3 KEYNOTE-689 trial, the results of which were presented at the American Association for Cancer Research (AACR) Annual Meeting on April 27, 2025. At the trial’s first pre-specified interim analysis, KEYTRUDA before surgery (neoadjuvant), then continued after surgery (adjuvant) in combination with standard of care (SOC), RT with or without cisplatin, followed by KEYTRUDA alone, reduced the risk of event-free survival (EFS) events (defined as disease recurrence, disease progression, or death) by 30% (HR=0.70 [95% CI, 0.55–0.89]; p=0.00140) in patients whose tumors expressed PD-L1 (CPS ≥1) compared to adjuvant SOC. Among the CPS ≥1 population, median EFS was 59.7 months (95% CI, 37.9-not reached) in the KEYTRUDA arm versus 29.6 months (95% CI, 19.5-41.9) in the SOC arm.

“The introduction of KEYTRUDA as a perioperative treatment option for certain patients with resectable locally advanced head and neck squamous cell carcinoma represents a potentially significant shift in how we manage this disease,” said Dr. Ravindra Uppaluri, the study’s overall principal investigator, director of Head and Neck Surgical Oncology, Brigham and Women’s Hospital and Dana-Farber Cancer Institute. “With this approval, we can now offer appropriate patients with resectable locally advanced head and neck squamous cell carcinoma a new treatment regimen that has been shown to reduce the risk of recurrence, progression, or death by 30%, compared with standard of care adjuvant chemoradiotherapy or radiotherapy alone.”

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously. Immune-mediated adverse reactions can occur at any time during or after treatment with KEYTRUDA, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, other transplant (including corneal graft) rejection, and complications of allogeneic hematopoietic stem cell transplantation. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of KEYTRUDA. Based on the severity of the adverse reaction, KEYTRUDA should be withheld or permanently discontinued and corticosteroids administered if appropriate. KEYTRUDA can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. 

“As the first perioperative anti-PD-1 treatment option for appropriate patients with resectable locally advanced head and neck squamous cell carcinoma, this new treatment regimen has the potential to shift the treatment paradigm for patients and their families affected by this disease,” said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. “Based on these trial results, KEYTRUDA as part of this regimen shows potential to change long-standing standards of care for treating certain patients with locally advanced HNSCC.”

This approval was reviewed under Project Orbis, an initiative of the FDA Oncology Center of Excellence that provides a framework for concurrent review of oncology drugs among its international partners. Under Project Orbis, marketing authorization applications for KEYTRUDA based on the results of KEYNOTE-689 are under review by health authorities in Israel, Canada, Australia, Singapore, Brazil and Switzerland. Marketing Authorization Applications are also under review by regulatory authorities worldwide, including Europe and Japan.

In the U.S., KEYTRUDA is currently approved as monotherapy and in combination regimens for certain patients with recurrent or metastatic HNSCC as follows:

• KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC;
• KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test; and
• KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Head and neck cancer describes a number of different tumors that develop in or around the throat, larynx, nose, sinuses and mouth. In the U.S., it is estimated there will be approximately 72,680 new cases of head and neck cancer diagnosed and more than 16,680 deaths from the disease in 2025. These data include cancers of the oral cavity, pharynx and larynx. Most head and neck cancer is squamous cell carcinoma which begins in the flat, squamous cells that make up the thin mucosal lining of the head and neck. Locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is cancer that has spread from where it started to nearby tissue or lymph nodes but has not yet spread to distant parts of the body. There are several factors that greatly increase the risk of developing head and neck cancer, including tobacco and alcohol use and human papillomavirus (HPV).