Overexpression of the
epidermal growth factor receptor (EGFR) is a common characteristic of
head and neck squamous cell carcinomas (
HNSCC).
Cetuximab is a chimeric anti-EGFR
monoclonal antibody (mAb) with multiple approved indications in
HNSCC, including with
radiation therapy (RT) for locoregionally advanced disease, as monotherapy after
platinum progression, and with
platinum/
5-fluorouracil for recurrent or metastatic disease. There remain, however, numerous unanswered questions regarding the optimal use of
cetuximab in
HNSCC, including patient selection, its mechanisms of action and resistance, the effect of human papillomavirus status on outcomes, its role when combined with
induction chemotherapy or adjuvant radiation, and optimal management of skin toxicity and
hypersensitivity reactions. In addition, a variety of other anti-EGFR agents (the multitargeted small molecule
tyrosine kinase inhibitors [TKIs]
lapatinib,
dacomitinib, and
afatinib and the anti-EGFR mAbs
zalutumumab,
nimotuzumab, and
panitumumab) are currently under investigation in phase II and III clinical trials in different
HNSCC therapeutic settings. The anti-EGFR TKI
erlotinib is currently in phase III development for
oral cancer prevention. Numerous other drugs are in earlier stages of development for
HNSCC treatment, including novel anti-EGFR mAbs (
MEHD7945A,
necitumumab, and
RO5083945), small-molecule TKIs (
vandetanib,
icotinib, and
CUDC-101), EGFR antisense, various add-on
therapies to radiation and
chemotherapy (
bevacizumab,
interleukin-12,
lenalidomide,
alisertib, and VTX-2337), and drugs (
temsirolimus,
everolimus,
OSI-906,
dasatinib, and PX-866) intended to overcome resistance to anti-EGFR agents. Overall, a wealth of clinical trial data is expected in the coming years, with the potential to modify significantly the approach to anti-EGFR
therapy for
HNSCC.