Systemic Targeted Treatments for Basal Cell Carcinoma.

The sonic hedgehog (SHH) inhibitors vismodegib and sonidegib are the only 2 first-line systemic medications approved for the treatment of locally aggressive basal cell carcinoma (BCC). Vismodegib is the only SHH inhibitor approved for metastatic BCC. Cemiplimab, an immune checkpoint inhibitor (ICI), is now an approved second-line therapy for locally advanced or metastatic BCC. Efficacy and adverse effect profiles of vismodegib and sonidegib appear comparable, although head-to-head clinical trials have not been conducted. Despite the remarkable efficacy demonstrated by the 2 SHH inhibitors, adverse effects are common and often lead to treatment discontinuation. Alternative dosing schedules may help to manage these side effects, with recent approval of dose interruptions of up to 8 weeks. Given the high rate of recurrence and emerging concern regarding drug resistance, maintenance dosing regimens and potential synergism with other treatment modalities, such as radiotherapy or antifungal therapy, should be further explored. The use of SHH inhibitors in the neoadjuvant setting also is warranted, as it may allow for surgical management of previously inoperable cases of BCC.