Immunotherapy for head and neck cancer: from recurrent/metastatic disease to (neo)adjuvant treatment in surgically resectable tumors

We aim to summarize the current evidence on the role of immune checkpoint inhibitors in the (neo)adjuvant treatment of squamous cell carcinoma of the head and neck (HNSCC), with a particular focus on surgically treated patients.Pembrolizumab +/- chemotherapy improves the outcome in patients with previously untreated recurrent/metastatic HNSCC. Nivolumab is superior to chemotherapy after platinum failure. The addition of avelumab to chemoradiation failed to improve the outcome in patients with locally advanced HNSCC. Neoadjuvant presurgical programmed cell death 1 receptor (PD-1) blockade is safe and associated with encouraging overall response rate. KEYNOTE-689 randomizes patients with resectable stage III/IVA HNSCC to surgery and adjuvant standard of care +/- neoadjuvant and adjuvant pembrolizumab. ADHERE assigns surgically treated HNSCC at high risk of recurrence to chemoradiotherapy (CRT) and either durvalumab or placebo. MK-3475-689 evaluates the role of pembrolizumab in patients with resectable HNSCC. NIVOPOSTOP evaluates the addition of nivolumab to CRT in patients with surgically treated pStage III/IV HNSCC or pT3N1/pT4N1 oropharyngeal cancer with at least 20 packs/year at high risk of relapse.Multiple trials are currently evaluating the role of immunotherapy in HNSCC amenable to surgery. Neoadjuvant presurgical PD-1 blockade is feasible and safe and is associated with an encouraging overall response rate.