EGFR belongs to the ErbB family of
receptor tyrosine kinases and is associated with worse prognosis in
head and neck squamous cell carcinoma (
HNSCC).
Cetuximab is a
monoclonal antibody to the extracellular domain of EGFR and inhibits its downstream actions via multiple mechanisms. Besides its proven efficacy in locally advanced and incurable
HNSCC,
cetuximab has the distinct advantage of having a relatively tolerable side effect profile and not potentiating radiation toxicity. Though
therapies for advanced
HNSCC are evolving, locoregional recurrence and/or distant
metastases occur in a large percentage of patients. Though some patients can be salvaged with surgery or
radiation therapy, the majority are incurable, and are treated palliatively with systemic
therapy. In the setting of first line
therapy for recurrent/metastatic
HNSCC, the EXTREME trial provided level 1 evidence that
cetuximab improves overall survival when combined with cisplatinum and 5 FU. Following progression on first line
chemotherapy, several phase II trials suggest that
cetuximab monotherapy is a reasonable choice in this setting. Future studies should concentrate on clinical and molecular markers that may allow more personalized approaches to treating
HNSCC, and combining EGFR inhibitors with other agents in a synergistic approach.