Current Aspects and Future Considerations of EGFR Inhibition in Locally Advanced and Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck

SIMPLE SUMMARY: Squamous cell carcinoma of the head and neck (SCCHN) is a debilitating disease that affects hundreds of thousands of individuals worldwide and has a high mortality rate. Mainstay treatment largely consists of surgery, radiation, and chemotherapy which has been met with significant morbidity. The epidermal growth factor receptor is one that which plays a major role in cell signaling and has been extensively studied in locally advanced (LA) and recurrent metastatic (RM) SCCHN. This review paper details the major roles of the epidermal growth factor receptor (EGFR), previous and current EGFR inhibition therapeutics, resistance mechanisms, and the possible integration of immunotherapy and EGFR inhibition in this disease process. ABSTRACT: Recurrent metastatic (RM) and locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN) are devasting disease states with limited therapeutic options and poor overall survival. Targeting the epidermal growth factor receptor (EGFR) is one area that has helped improve outcomes in this disease. Anti-EGFR based therapies have been shown to improve overall survival and mitigate the significant toxicities incurred from standard radiation, chemotherapy, and/or surgical options. Cetuximab, the most well-studied anti-EGFR monoclonal antibody, has demonstrated a positive impact on outcomes for RM and LA SCCHN. However, the development of early resistance to cetuximab highlights the need for a wider arsenal of therapy for RM and LA diseases. The use of immune checkpoint inhibitors has recently transformed the treatment of recurrent SCCHN. Drugs such as pembrolizumab and nivolumab have demonstrated success in recent clinical trials and have been approved for the treatment of advanced disease. Given the positive results of both EGFR targeted agents and immune checkpoint inhibitors, ongoing trials are studying their synergistic effects.