Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer

Area of Science:

• Oncology
• Immunotherapy
• Head and Neck Cancer

Background:

• The efficacy of perioperative pembrolizumab combined with standard care for locally advanced head and neck squamous cell carcinoma (HNSCC) remains uncertain.
• Standard care typically involves surgery, adjuvant radiotherapy, and potentially chemotherapy.

Purpose of the Study:

• To evaluate the impact of adding neoadjuvant and adjuvant pembrolizumab to standard care on event-free survival in patients with locally advanced HNSCC.
• To assess the effect of pembrolizumab on surgical completion rates and safety profiles.

Main Methods:

• A phase 3, open-label trial randomly assigned patients with locally advanced HNSCC to receive standard care plus pembrolizumab or standard care alone.
• Pembrolizumab was administered as 2 cycles neoadjuvant and 15 cycles adjuvant therapy.
• The primary endpoint was event-free survival, analyzed across different programmed death-ligand 1 (PD-L1) combined positive score (CPS) populations (CPS≥10, CPS≥1, and all participants).

Main Results:

• Event-free survival at 36 months was significantly higher in the pembrolizumab group across all analyzed populations (CPS≥10: 59.8% vs. 45.9%; CPS≥1: 58.2% vs. 44.9%; total: 57.6% vs. 46.4%).
• The hazard ratio for progression, recurrence, or death favored the pembrolizumab group in all populations.
• Grade 3 or higher treatment-related adverse events were comparable between groups (44.6% vs. 42.9%), with a slightly higher incidence of death in the pembrolizumab group (1.1% vs. 0.3%).
• Potentially immune-mediated adverse events of grade 3 or higher occurred in 10.0% of the pembrolizumab group.

Conclusions:

• The addition of neoadjuvant and adjuvant pembrolizumab to standard care significantly enhances event-free survival in patients with locally advanced HNSCC.
• Pembrolizumab administration did not negatively affect surgical completion rates.
• The study identified no new safety concerns associated with perioperative pembrolizumab in this patient cohort.