Pembrolizumab (Keytruda; Merck) has received an FDA nod for adults with resectable locally advanced head and neck squamous cell carcinoma (HNSCC) whose tumors express PD-L1 combined positive score (CPS) ≥1, 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.1
The approval was based in part on efficacy data obtained in KEYNOTE-689 (NCT03765918), a randomized, multicenter, open-label trial of 714 patients with resectable locally advanced HNSCC [AJCC, 8th edition]. Patients were randomly assigned to either of the following:
- Neoadjuvant pembrolizumab every 3 weeks for 2 cycles followed by adjuvant pembrolizumab every 3 weeks for 3 cycles with RT, with or without cisplatin, and then every 3 weeks for 12 cycles of pembrolizumab as a single agent, or
- No neoadjuvant treatment prior to surgery followed by adjuvant RT with or without cisplatin
For patients whose tumors express PD-L1 CPS ≥1 (n=682), median event-free survival was 59.7 months (95% confidence interval, 37.9-not reached) in the pembrolizumab arm and 29.6 months (95% CI, 19.5-41.9) in the control arm.
While overall survival results were immature at the current analysis, with 76% of prespecified deaths in the CPS ≥1 population, no trend toward a detriment was observed.
Of the patients who received neoadjuvant pembrolizumab, 1.4% were unable to receive surgery due to adverse reactions compared with 1.4% in the control arm.
Reference
- FDA. FDA approves neoadjuvant and adjuvant pembrolizumab for resectable locally advanced head and neck squamous cell carcinoma [press release]. June 12, 2025. Accessed July 1, 2025. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvant-and-adjuvant-pembrolizumab-resectable-locally-advanced-head-and-neck
