Emerging monoclonal antibody therapy for head and neck squamous cell carcinoma.

The incidence of head and neck squamous cell carcinoma (HNSCC) is increasing, particularly among younger populations. It is projected that the number of new cases will increase by almost 50% by 2040, with market revenues expected to triple in the same period. Despite the recent introduction of immune checkpoint inhibitors (ICIs) into the therapeutic armamentarium, the vast majority of patients with recurrent and/or metastatic (R/M) HNSCC fail to derive durable benefits from systemic therapy. This article aims to review the multiple monoclonal antibodies (mAbs) regimens currently under development, targeting various growth factors, immune checkpoints, immune costimulatory receptors, and more. So far, the combination of anti-EGFR and ICI appears to be the most promising, especially in HPV-negative patients. It will be interesting to confirm whether the arrival of antibody-drug conjugates and bispecific mAb can surpass the efficacy of anti-EGFR, as they are also being tested in combination with ICI. Furthermore, we believe that immune costimulatory agonists and various ICIs combination are worth monitoring, despite some initial setbacks.