[Recent advances in the systemic treatment of head and neck cancers]

Head and neck squamous cell carcinoma (HNSCC) remains a malignancy with high global morbidity and mortality. Over the past decade, systemic treatment paradigms for recurrent/ metastatic (R/M) HNSCC have evolved significantly with the introduction of immuno- and targeted therapies. The phase III KEYNOTE-048 trial established pembrolizumab, alone or in combination with chemotherapy, as a new firstline standard in PD-L1 positive cases. In the second-line setting, the CheckMate 141 and KEYNOTE-040 trials confirmed the survival benefit and favorable safety profile of PD-1 inhibitors. The recent KEYNOTE-689 and NIVOPOSTOP studies highlight the potential role of perioperative and adjuvant immunotherapy in resectable, locally advanced HNSCC. However, multiple negative studies underscore the limitations of immune checkpoint inhibitors in the definitive treatment of locally advanced disease. Defining the optimal sequencing of systemic therapies remains a key clinical challenge in this patient population.