Keytruda Breaks New Ground with FDA Approval for Perioperative Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma
The FDA approved Keytruda (pembrolizumab) on June 12, 2025, for adult patients with resectable, locally advanced head and neck squamous cell carcinoma (HNSCC) whose tumors express PD-L1 with a combined positive score (CPS) of 1 or greater.
This approval is based on the phase 3 KEYNOTE-689 clinical trial, which enrolled 714 patients with resectable stage III-IVA HNSCC and compared perioperative pembrolizumab plus standard of care versus standard of care alone.
The perioperative regimen includes neoadjuvant pembrolizumab (2 cycles before surgery), adjuvant pembrolizumab combined with radiotherapy with or without cisplatin, followed by additional pembrolizumab monotherapy cycles after surgery.
Keytruda treatment significantly improved event-free survival (EFS), reducing risk of progression, recurrence, or death by 30% compared to standard care (hazard ratio 0.70) in patients with PD-L1 CPS ≥1.
Median EFS was 59.7 months in the pembrolizumab arm versus 29.6 months in the standard care arm for PD-L1–positive patients.
The safety profile was manageable and consistent with known pembrolizumab effects, with similar rates of treatment-related adverse events compared to standard care.
This approval represents the first perioperative anti-PD-1 treatment option for resectable locally advanced HNSCC and is expected to change the longstanding treatment paradigm for this patient population.
Additional approved indications for Keytruda in HNSCC include first-line treatment for metastatic or unresectable recurrent disease in combination therapy or as monotherapy in PD-L1 positive tumors.