The Treatment Landscape and Management of HNSCC

Contemporary head and neck squamous cell carcinoma (HNSCC) treatment employs multimodal approaches tailored to disease stage and location. For locally advanced disease confined to the head and neck region, treatment typically combines surgery, radiation, and chemotherapy with cisplatin as the standard agent. Recent FDA approval of immunotherapy for high-risk patients represents a significant advancement, introducing pembrolizumab or nivolumab before and after surgery to improve outcomes. The treatment sequence may vary, with some patients receiving upfront surgery followed by adjuvant therapy, while others undergo chemoradiation with surgery reserved for salvage situations.

Recurrent or metastatic HNSCC presents greater therapeutic challenges, with immune checkpoint inhibitors such as pembrolizumab and nivolumab serving as first-line treatments. These immunotherapies work by enhancing the immune system's ability to recognize and eliminate cancer cells but demonstrate efficacy in only 20% to 30% of patients. The limited response rates highlight the urgent need for additional therapeutic options, particularly for patients who progress after standard treatments, including surgery, radiation, chemotherapy, and immunotherapy.

The treatment landscape reflects the evolution from traditional cytotoxic approaches to more targeted and immune-based strategies. However, patients who exhaust standard options face limited alternatives, often requiring older chemotherapy agents with significant adverse effects or enrollment in clinical trials. This therapeutic gap underscores the importance of clinical research and novel drug development, particularly for antibody-drug conjugates and other targeted therapies that may offer improved efficacy with reduced toxicity compared with conventional treatments.