Clinical Application of EGFR Inhibitors in Head and Neck Squamous Cell Cancer

Abstract

Epidermal growth factor receptor (EGFR) signaling inhibition represents a highly promising arena for the application of molecularly targeted cancer therapies. Evolving from several decades of systematic research in cancer cell biology, a series of EGFR inhibitors from both the monoclonal antibody (mAb) and tyrosine kinase inhibitor (TKI) class have been developed and entered the clinic. Four EGFR inhibitors have recently gained FDA approval for cancer therapy in the United States (and many other countries) including the mAbs cetuximab (Erbitux) and panitumumab (Vectibix), and the small molecule TKIs gefitinib (Iressa) and erlotinib (Tarceva). The rapidly expanding preclinical and clinical data supporting the FDA drug registrations validate a central role for the EGFR as an important molecular target in epithelial malignancies. In this report, we highlight the relevant aspects of EGFR biology and the translation of these observations into recent treatment advances in head and neck squamous cell cancer (HNSCC). Key recent clinical findings include a survival advantage for the addition of the anti-EGFR monoclonal antibody cetuximab to definitive radiation therapy in patients with locoregionally advanced HNSCC, and palliative benefits for the use of cetuximab in patients with incurable HNSCC. Small molecule EGFR TKIs also show considerable promise in this disease, alone and in combination with radiation and chemotherapy. Both classes of anti-EGFR agent are generally well-tolerated with side effects (notably skin rash) that are distinct from those of conventional chemotherapy. Recently completed and ongoing clinical trials will continue to refine the role for EGFR inhibitors in all treatment phases of HNSCC [1, 2]. Concurrent chemoradiation has emerged worldwide as a standard of care for many patients with locoregionally advanced HNSCC [3]. With state-of-the-art radiation (RT) and chemotherapy (along with nodal dissection and salvage surgery, when appropriate) multidisciplinary teams regularly achieve cure rates of approximately 40–50% for stage III and 30% for stage IV HNSCC patients [4] with recently published studies showing even better disease-free and overall 7 Clinical Application of EGFR Inhibitors in Head and Neck Squamous Cell Cancer