A review of the safety, efficacy, and administration of hedgehog inhibitors for the treatment of advanced basal cell carcinoma: an expert consensus panel

BACKGROUND: Hedgehog inhibitors (HHIs) are approved for the treatment of locally advanced BCCs in patients who are not surgical candidates or have had recurrence following surgical treatment. This expert consensus panel further characterizes the efficacy and safety of HHIs while also providing clinical guidance on their appropriate dosing, laboratory monitoring, and supplementation. METHODS: A comprehensive literature review was completed on November 1, 2024 using the keywords "basal cell carcinoma," "hedgehog inhibitor," "sonidegib," and "vismodegib". An expert panel of nine dermatologists reviewed and assigned levels of evidence to the relevant articles and created consensus statements regarding HHIs, with correlating strength of recommendations, using the modified Delphi process. RESULTS: Of the 304 articles identified, 23 articles met the selection criteria and were included for review. The panel unanimously adopted nine consensus statements and recommendations, of which three were given a strength of recommendation of "A", two were given a "B", and four were given a "C". CONCLUSION: Sonidegib and vismodegib have similar efficacy in treating advanced BCC, but sonidegib has lower rates and a greater delay in onset of AEs. Sonidegib has a significantly greater volume of distribution and half-life than those of vismodegib. Dosing interruptions have not been shown to reduce the efficacy of HHIs, and L-carnitine supplementation can help reduce the incidence of muscle spasms.