Immunotherapy Approved as First Perioperative Approach in Locally Advanced Head and Neck Cancer

The FDA has approved pembrolizumab for certain patients with previously untreated head and neck cancer.

The U.S. Food and Drug Administration (FDA) has approved pembrolizumab (Keytruda) for the treatment of adult patients with resectable locally advanced head and neck squamous cell carcinoma (HNSCC) that has not previously been treated and expresses PD-L1. The approval requires that pembrolizumab be given as a single agent before surgery, in combination with radiation therapy and/or chemotherapy after surgery, and subsequently continued as monotherapy.

Pembrolizumab is a type of immunotherapy called an immune checkpoint inhibitor that blocks the PD-1 receptor that acts as a “brake” on T cells, preventing its interaction with and activation by PD-L1. This enables pembrolizumab to support more effective immune responses against tumors. This is the first perioperative (before and after surgery) approval for patients with locally advanced HNSCC.

Pembrolizumab was approved to be given before and after surgery for certain patients with head and neck cancer.

The approval is based on results from the randomized, multicenter, open-label phase III KEYNOTE-689 trial, which enrolled 714 patients with resectable stage 3 or stage 4a HNSCC. Patients in both arms of the trial underwent surgery and then received radiation therapy and, if their tumor had high-risk features, chemotherapy. Additionally, patients were randomly assigned (1:1) to receive pembrolizumab both before and after surgery, or no additional treatment. In both groups, 1.4% of patients were unable to receive surgery due to adverse reactions.

In patients whose tumors were PD-L1-positive, the addition of perioperative pembrolizumab reduced the risk of an event—defined as disease progression that precluded surgery, disease progression or recurrence, or death due to any cause—by 30% versus the control treatment regimen. Half of the patients in the pembrolizumab arm remained event-free for at least 59.7 months, compared with 29.6 months for patients in the control arm. These results were first presented at the AACR Annual Meeting 2025 and featured in an AACR blog post and press release.

The recommended dose for pembrolizumab is 200 mg every three weeks or 400 mg every six weeks, to be given prior to chemotherapy on days when both are administered.

Head and neck cancers are cancers that arise in tissues of the head and neck, namely the oral cavity or throat, larynx, nasal cavity, sinuses, and salivary glands. According to federal statistics, it was estimated that 59,660 individuals would be diagnosed with cancers of the oral cavity and pharynx and 13,020 individuals would be diagnosed with laryngeal cancer, and that approximately 12,770 patients would die of cancers of the oral cavity and pharynx and 3,910 patients would die of laryngeal cancer in the United States in 2025.

The FDA rendered its decision on June 12, 2025. Check this resource for updated information on all therapeutics regulated by the FDA.