Preoperative immunotherapy for head and neck cancers: state of art

Programmed cell death 1 (PD-l)-targeting agents have been FDA-approved for treatment of recurrent/ metastatic head and neck squamous cell carcinoma (HNSCC). Clinical studies employing these agents preoperatively for HNSCC in the definitive setting are emerging and have important implications.

Preclinical studies demonstrate enhanced effectiveness of preoperative PD-1 targeting compared with postoperative treatment. Nine HNSCC clinical studies evaluating preoperative treatment with PD-1-targeted pembrolizumab/nivolumab alone or in combination therapy were recently reported. These studies differed by preoperative treatment type and duration and reported no surgical delays, no unexpected surgical complications and grade 3-4 immune-related adverse events consistent with the employed immunotherapeutic agent(s). Rates of major pathologic response (MPR), reduced residual viable tumour to 10% or less, ranged from 2.9-31% across eight trials without neoadjuvant radiation therapy. Higher PD-1 ligand (PD-L1) expression, increased inflammatory gene expression and enhanced immune cell tumour infiltration in baseline biopsies were associated with pathologic tumour response (pTR) in some studies. Any degree of pTR was associated with improved survival/relapse outcomes in two studies.

Emerging preoperative anti-PD-1 HNSCC clinical studies indicate that preoperative treatment does not impact surgical management. Defining predictive biomarkersand tumour pathologic response implications for patient survival are areas for further investigation.