Sandra Llop, Pablo Jiménez-Labaig, Ilaria Micheletto, Nabil F. Saba, Ben O’Leary
The prognosis of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) remains poor, with most patients presenting with primary or acquired resistance to immune checkpoint inhibitors (ICIs). Upon progression on ICIs, the only standard of care treatment options are chemotherapy ± cetuximab combinations with high toxicity rates and limited efficacy, underscoring the urgent need for more effective and tolerable therapeutic strategies. This review explores the landscape of rapidly evolving novel treatment approaches in recurrent/metastatic HNSCC, including ICI combinations, therapeutic vaccines, injectable drugs, bispecific antibodies, antibody-drug conjugates, multitargeted kinase inhibitors and new targeted therapy agents.