The U.S. Food and Drug Administration (FDA) has approved pembrolizumab (Keytruda) on June 12, 2025, for the perioperative treatment of resectable, PD-L1-expressing (combined positive score [CPS] ≥1) locally advanced head and neck squamous cell carcinoma (HNSCC) in adult patients. This approval represents the first new therapy in the head and neck cancer field in six years and the debut of immunotherapy in the perioperative treatment of locally advanced HNSCC.
Pembrolizumab, a PD-1 immune checkpoint inhibitor, will be used as neoadjuvant therapy before surgery. Post-surgery, it will be combined with radiotherapy (with or without cisplatin), followed by continued monotherapy. This decision is based on the results of the phase 3 KEYNOTE – 689 clinical trial. The trial showed that among patients with PD-L1 (CPS ≥1), the average event-free survival (EFS) in the pembrolizumab group was 59.7 months, compared to 29.6 months in the control group, reducing the risk of recurrence or death by 30%. Additionally, a statistically significant improvement in pathological major response rate (mPR) was observed in the pembrolizumab treatment group.
In terms of safety, among patients who received preoperative pembrolizumab, 18% experienced grade 3 or higher treatment-related adverse events, highlighting the importance of careful patient monitoring during therapy. This breakthrough provides a new, potentially more effective treatment option for patients with locally advanced HNSCC, offering hope for improved long-term outcomes.
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