Drug therapy of advanced cutaneous squamous cell carcinoma: is there any evidence?

There are few randomized controlled studies to guide the treatment of advanced cutaneous squamous cell carcinoma. The existing treatments are mostly based on case reports and small case series. Here we review recently available insights concerning the treatment of locally advanced and metastatic squamous cell carcinoma, with a special emphasis on novel targeted therapy and immunotherapy.

Surgery and combination of chemotherapy and radiation therapy have been long considered the gold standard options for advanced squamous cell carcinoma. The detection of clinically relevant driver mutations has opened the door to the use of novel targeted therapies. Recent studies have shown that aggressive cutaneous squamous cell carcinoma is characterized by a very high mutational background. Furthermore, the importance of the defective immunosurveillance in the growth of cutaneous squamous cell carcinoma and the critical role of programed cell death protein 1 and programmed death-ligand 1 interaction in skin tumor development provides a rationale for the use of immune checkpoint inhibitors.

Epidermal growth factor receptor inhibitors have shown to have satisfactory antitumor activity with acceptable side-effect profile. However, their place in management of advanced cutaneous squamous cell carcinoma alone or in combination with either radiation therapy and/or chemotherapy needs to be better characterized. The available preliminary findings suggest that immune checkpoint inhibitors represent a potentially valuable alternative in cutaneous aggressive squamous cell carcinoma, promising a further expansion of their indication spectrum. Randomized controlled studies will allow us to better characterize their practical value.