Efficacy and Safety of Hedgehog Inhibitors for Advanced Basal Cell Carcinoma: An Expert Consensus Panel

May 2025 | Volume 24 | Issue 5 | 465 | Copyright © May 2025


Published online April 28, 2025

doi:10.36849/JDD.8827

Joshua Burshtein MDa, Milaan Shah MDb, Danny Zakria MD MBAc, Scott Dinehart MDd, Jesse Lewin MDc, George Monks MDe, Michael Mortazie DOf, Shannon Trotter DOg, Todd Schlesinger MDh, Mark Lebwohl MDc, Darrell Rigel MD MSi

aDepartment of Dermatology, University of Illinois-Chicago, Chicago, IL
bDepartment of Dermatology, Medical University of South Carolina, Charleston, SC
cDepartment of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY
dArkansas Dermatology, Little Rock, AR
eDepartment of Dermatology, University of Oklahoma College of Medicine in Oklahoma City, OK
fBennett Surgery Center, Santa Monica, CA
gOhio University Heritage College of Osteopathic Medicine, Athens, OH
hClinical Research Center of the Carolinas, Charleston, SC
iDepartment of Dermatology, NYU Grossman School of Medicine, New York, NY

Abstract
Background: Hedgehog inhibitors (HHIs) can be used to treat patients with locally advanced basal cell carcinoma (laBCC) who are not candidates for surgery or radiation or whose tumors have recurred following radiation or surgery. The purpose of this expert consensus panel is to guide HHI usage, thereby informing clinical decision-making and optimizing patient care.
Methods: A comprehensive literature search was completed on May 1, 2024, using the keywords "basal cell carcinoma," "hedgehog inhibitor," "sonidegib," and "vismodegib". A panel of eight dermatologists with significant expertise in the treatment of BCC gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned.
Results: The literature search produced 200 articles. A screening of the studies resulted in 19 articles that met the criteria. The panel unanimously voted to adopt 8 consensus statements and recommendations, two were given a strength of "A", three were given a strength of "B", and three were given a strength of "C".
Conclusion: Sonidegib and vismodegib are FDA-approved HHIs that can decrease the size of laBCC tumors prior to surgical intervention or be used as primary therapy in certain circumstances. The most common adverse events include muscle spasms, alopecia, and taste alterations.

Citation: Burshtein J, Shah M, Zakria D, et al. Efficacy and safety of hedgehog inhibitors for advanced basal cell carcinoma: an expert consensus panel. J Drugs Dermatol. 2025;24(5):465-471. doi:10.36849/JDD.8827

INTRODUCTION

Basal cell carcinoma (BCC) is the most prevalent cancer worldwide.1 The mainstay of treatment is surgical excision or Mohs micrographic surgery but patients may develop advanced BCC such that surgical intervention, curettage, electrodesiccation, radiotherapy, or superficial field therapies are not practical.2 Locally advanced BCC (laBCC) tumors are aggressive BCCs that are large, grow deep into tissue, and/or are in difficult-to-treat locations.2 Patients with laBCC who receive surgical treatment may result in damaging deformities, loss of function, and substantial morbidity.2-4

Hedgehog inhibitors (HHIs) have emerged as a treatment option for patients with laBCC who are not candidates for surgery or radiation therapy or whose tumors have recurred following radiation or surgery.5 There are two oral HHIs currently approved by the FDA, vismodegib (approved 2012) and sonidegib (approved 2015).6-8 Despite known efficacy, HHIs have a high discontinuation rate due to adverse events.6,9 The purpose of this expert consensus panel was to review the literature on HHIs to provide guidance on their usage, thereby informing clinical decision-making and optimizing patient care in the management of BCC. As there are no head-to-head trials between vismodegib and sonidegib, the comparison between the two drugs by the expert panel was limited to available published literature.

MATERIALS AND METHODS

Literature Search and Study Selection
A comprehensive literature search of PubMed, Scopus, and Google Scholar was completed on 
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