FDA

Keytruda approved for perioperative treatment of head and neck squamous cell carcinoma

June 17, 2025

FDA approved Keytruda (pembrolizumab) for adults with resectable locally advanced head and neck squamous cell carcinoma (HNSCC) whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1) 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.

Efficacy

Efficacy was evaluated in KEYNOTE-689 (NCT03765918), a randomized, multicenter, open-label trial involving 714 patients with resectable locally advanced (Stage III-IVA) HNSCC. Patients were randomized (1:1) to either of the following:

• neoadjuvant pembrolizumab q3wks for 2 cycles followed by adjuvant pembrolizumab q3wks for 3 cycles with RT, with or without cisplatin, and then q3wks for 12 cycles of pembrolizumab as a single agent, or
• no neoadjuvant treatment prior to surgery followed by adjuvant RT with or without cisplatin.

On both treatment arms, patients received cisplatin with adjuvant RT if high-risk pathological features (i.e., positive margins <1 mm or extranodal extension) were present at surgery.

The major efficacy measure was event-free survival (EFS) by blinded independent central review defined as the time from randomization to the first occurrence of any of the following events: disease progression precluding definitive surgery, local or distant disease progression or recurrence, or death due to any cause. Additional efficacy outcome measures included overall survival (OS). For patients whose tumors express PD-L1 CPS ≥1 (n=682), median EFS was 59.7 months (95% confidence interval [CI], 37.9, not reached [NR]) in the pembrolizumab arm and 29.6 months (95% CI, 19.5, 41.9) in the control arm (hazard ratio, 0.70; 95% CI, 0.55, 0.89; p-value, 0.00140).

While OS results were immature at the current analysis, with 76% of pre-specified deaths in the CPS ≥1 population, no trend towards a detriment was observed.

Safety

Of the patients who received neoadjuvant pembrolizumab, 1.4% were unable to receive surgery due to adverse reactions vs. 1.4% on the control arm. The Prescribing Information for pembrolizumab includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, and embryo-fetal toxicity. Adverse reactions were consistent with prior experience with pembrolizumab.

Recommended dose

The recommended dosage of pembrolizumab is 200 mg q3wks or 400 mg q6wks. Pembrolizumab should be administered prior to chemotherapy when given on the same day.

Sources:

FDA approves neoadjuvant and adjuvant pembrolizumab for resectable locally advanced head and neck squamous cell carcinoma. [News release]. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvant-and-adjuvant-pembrolizumab-resectable-locally-advanced-head-and-neck

Keytruda (pembrolizumab). [package insert]. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/125514s183lbl.pdf Revised June 2025. Accessed June 16, 2025.

FDA approves Keytruda® (pembrolizumab) for PD-L1+ resectable locally advanced head & neck squamous cell carcinoma as neoadjuvant treatment, continued as adjuvant treatment combined with radiotherapy with or without cisplatin then as a single agent. [News release]. 2025. https://www.merck.com/news/fda-approves-keytruda-pembrolizumab-for-pd-l1-resectable-locally-advanced-head-neck-squamous-cell-carcinoma-as-neoadjuvant-treatment-continued-as-adjuvant-treatment-combined-with-radiother/