Clinical efficacy and immunological aspects of neoadjuvant and perioperative therapy in resectable head and neck carcinoma

Checkpoint inhibitor (CPI) therapy has emerged as treatment option in selected patients with resectable head and neck squamous cell carcinoma. Recent phase III data have led to approval of perioperative pembrolizumab for patients with PD-L1-positive (CPS ≥ 1). With emerging data on adjuvant checkpoint inhibitor therapy the selection of the optimal treatment strategy is becoming increasingly complex. Several clinical phase II/III trials have evaluated neoadjuvant immunotherapy in resectable head and neck cancer, demonstrating both clinical and immunological benefits. This review summarizes current data on neoadjuvant and perioperative checkpoint inhibitors in resectable head and neck cancer and addresses main immunological advantages. In addition, potential strategies to optimize treatment efficacy and to overcome resistance mechanisms of CPI therapy are discussed. Further trials are needed to define optimal treatment protocols, determinate the best timing of surgery, and identify reliable biomarkers for patient selection, to guide evidence-based therapeutic decision-making in routine clinical practice.