Emerging trends in the treatment of advanced basal cell carcinoma

Basal cell carcinoma (BCC) is the most commonly diagnosed skin cancer worldwide. In most patients, BCC can be effectively treated with standard surgical excision, Mohs micrographic surgery, curettage and electrodessication, radiotherapy, and/or superficial field therapies (including 5-fluorouracil, imiquimod, and photodynamic therapy); however, a minority of patients develop advanced BCC, for which treatment can be challenging and outcomes are poorer. Advanced BCC encompasses a heterogeneous assortment of cases, including metastatic BCC as well as locally advanced BCC (for which no formal definition exists but which generally includes large, deep, aggressive, or recurrent tumors). Locally advanced BCC may be broadly categorized as cases for which (further) surgery is considered inappropriate or would be substantially disfiguring and radiation is considered inappropriate as a single modality or second-line treatment. Several therapies are being investigated for the treatment of advanced BCC. In particular, hedgehog pathway inhibitors have emerged as an important treatment option for this population. Two hedgehog pathway inhibitors-vismodegib and sonidegib-have received regulatory approval for the treatment of certain subsets of patients with advanced BCC after demonstrating clinical efficacy and safety in large, international phase 2 clinical trials. Here we review the available treatment options for BCC, focusing on the treatment of advanced BCC. Clinical data from studies evaluating vismodegib and sonidegib in patients with advanced BCC are also discussed. As more clinical trial and real-world data on the use of hedgehog pathway inhibitors become available, better-informed decisions can be made for the treatment of patients with advanced BCC.