Comparison of Smoothened Inhibitors in Treating Basal Cell Carcinoma: A Survey Study of Multidisciplinary Expert Opinions and Clinical Experiences

Smoothened inhibitors (SMOi), also known as hedgehog inhibitors (HHI), are targeted therapies that have transformed the locally advanced BCC and metastatic BCC treatment landscape. Landmark studies ERIVANCE and BOLT facilitated FDA approval of vismodegib in 2012 and sonidegib in 2015, respectively, and provided valuable insights into SMOi efficacy, dosing, pharmacokinetics, and adverse effects (AE). However, study differences have caused wide variability in treatment utilization. Nuanced clinical interpretation is critical. A 35-item RedCAP survey was released in Spring 2024 via email to the Skin Cancer Outcomes Consortium. Twenty-nine clinicians who treat advanced BCC responded. The majority of respondents (58.3%) indicated that they believed that vismodegib and sonidegib are similar therapeutic options for laBCC and mBCC. Similarly, 45.8% believed both SMOi to have similar tolerability, followed by 29.9% who believed sonidegib to be somewhat more tolerable than vismodegib. When asked, “All things considered, which drug do you believe is superior for treating locally advanced BCC?” 41.7% responded that they believed them to be similar, 25% said ‘I don’t know’, 20.8% chose sonidegib, and only 12.4% chose vismodegib. However, reported prescribing habits paradoxically favored vismodegib, with 54.5% of clinicians primarily prescribing vismodegib, 36.4% preferring sonidegib, and only 9.1% endorsing prescribing both equally. These findings highlight the lack of uniformity, as well as familiarity, with the therapeutic options of SMOi for advanced BCC. Updating SMOi clinical guidelines and the creation of management strategies, including considerations for AE, dosing options, and drug switching, are needed to improve and standardize patient care.