Systemic Targeted Treatments for Basal Cell Carcinoma

Abstract

The sonic hedgehog (SHH) inhibitors vismodegib and sonidegib currently are the only 2 oral medications approved by the US Food and Drug Administration for the first-line treatment of locally advanced basal cell carcinoma (BCC). Vismodegib also is approved for metastatic BCC.• Cemiplimab, a programmed cell death protein 1 inhibitor, is now an approved treatment for patients with advanced BCC refractory or intolerant to SHH inhibitor therapy.• Adverse effects of SHH inhibitors, most commonly muscle spasms, often lead to treatment discontinuation, but intermittent dosing regimens can be used to increase tolerability and adherence.• Combining SHH inhibitors with radiotherapy or antifungal therapy as well as maintenance dosing strategies may help reduce the risk of recurrence.• Neoadjuvant administration of a SHH inhibitor may enable surgical excision of previously inoperable cases through tumor shrinkage.

Supraorbital Basosquamous Carcinoma Treated with Cemiplimab Followed by Sonidegib: A Case Report and Review of the Literature

“…The squamous cell component of BSC could justify the greater aggressiveness of this subtype as well as the good response of this tumor to anti-PD-1; basal cell component may require a more targeted therapy to be eradicated. Hedgehog signaling pathway inhibitors are currently the only two systemic drugs approved as first-line therapy in BCC [10][11][12]. Reinhard Dummer et al, in the phase II BOLT trial, evaluated the long-term efficacy and safety of Sonidegib in patients with advanced BCC who were not candidates for surgery or radiation therapy.…”

“…A small percentage develop advanced BCC, for which systemic therapy is indicated. Hedgehog Pathway Inhibitors (HHI), Vismodegib and Sonidegib, are the only two systemic drugs approved as first-line treatments for locally advanced BCC, while Vismodegib is the only HHI approved for metastatic BCC [10][11][12]. These two HHIs have similar efficacy profiles but differing pharmacokinetic characteristics, such as half-life and volume of distribution, which result in Sonidegib exhibiting a broader distribution within the skin in comparison to Vismodegib and better tolerability [13].…”