FDA Alert

FDA Approves Pembrolizumab for Adults with Resectable Locally Advanced Head, Neck Squamous Cell Carcinoma

Kate Young

The FDA announced its approval of pembrolizumab for adult patients with resectable locally advanced head and neck squamous cell carcinoma (HNSCC) whose tumors express PD-L1 as determined by an FDA-approved test on June 12, 2025.

This approval follows favorable safety and efficacy data from the randomized, multicenter, open-label KEYNOTE-689 trial. A total of 714 patients with resectable locally advanced HNSCC were randomized 1:1 with the first group receiving neoadjuvant pembrolizumab every 3 weeks for two cycles followed by adjuvant pembrolizumab every 3 weeks for three cycles with radiotherapy, and then every 3 weeks for 12 cycles of pembrolizumab as a single agent. The control group received no neoadjuvant treatment before surgery followed by adjuvant radiotherapy. Both groups received cisplatin with adjuvant radiotherapy if the patient had high-risk pathological features at surgery.

The addition of neoadjuvant and adjuvant pembrolizumab to standard treatment demonstrated a significant improvement in event-free survival (EFS). Median EFS was 59.7 months in the pembrolizumab arm compared with 29.6 months in the control arm, corresponding to a hazard ratio of 0.70 (95% CI, 0.55, 0.89; P = .0014), reflecting a 30% reduction in the risk of disease progression, recurrence, or death. Although overall survival results were immature at the time of analysis, with 76% of the pre-specified deaths observed, there was no evidence of a detrimental effect on survival in the pembrolizumab-treated group.

Just 1.4% of participants in both arms were unable to proceed to surgery due to adverse reactions. Adverse reactions were consistent with prior pembrolizumab experience, which includes prescribing warnings for immune-mediated adverse reactions, infusion-related reactions, and embryo-fetal toxicity.

The recommended dose for pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks, and it should be administered prior to chemotherapy when given on the same day.

Reference:
FDA approves neoadjuvant and adjuvant pembrolizumab for resectable locally advanced head and neck squamous cell carcinoma.US Food and Drug Administration.  Published June 13, 2025.