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

Comparison of Smoothened Inhibitors in Treating Basal Cell Carcinoma: A Survey Study of Multidisciplinary Expert Opinions and Clinical Experiences | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Short Report Comparison of Smoothened Inhibitors in Treating Basal Cell Carcinoma: A Survey Study of Multidisciplinary Expert Opinions and Clinical Experiences Kennedy H. Sun, Sonia P. Goyal, Brian Berman, Anne Lynn S. Chang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7623555/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract 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. basal cell carcinoma BCC laBCC mBCC smoothened inhibitors SMOi hedgehog inhibitors HHI vismodegib sonidegib Introduction Smoothened inhibitors (SMOi), also known as hedgehog inhibitors (HHI), are a targeted therapy that have transformed the treatment landscape for locally advanced BCC (laBCC) and metastatic BCC (mBCC). Landmark studies, ERIVANCE for vismodegib and BOLT for sonidegib, provided valuable insights into SMOi efficacy, dosing, adverse effects (AE), and pharmacokinetics [10,11]. Both drugs are administered orally once daily (vismodegib 150 mg, sonidegib 200 mg), but sonidegib requires fasting administration, has a longer elimination half-life (28-30 days vs. 4-12 days), and a larger volume of distribution. Muscle spasms, alopecia, and dysgeusia comprise some of the common, shared AE. [4] However, differences in study criteria and methods have caused variability in treatment utilization and require nuanced clinical interpretation. Additionally, while SMOi are effective, their use is often limited by AE [4]. Methods A 35-item anonymous REDCap survey was released in Spring 2024 via email to the Skin Cancer Outcomes Consortium. Information was collected regarding clinical practice setting, extent of experience treating advanced BCC with SMOi, comparisons of experiences with tolerability and AE, and preferences between these two FDA-approved options. Results Respondent demographics 29 clinicians who treat laBCC and mBCC in various fields within the United States responded (Dermatology 27.6%, Mohs surgeon 13.8%, Medical Oncologist 34.5%, Surgical Oncologist 10.3%, Other 6.9%, Head and Neck Surgeon 3.4%, Radiation Oncologist 3.4%) (response rate: 37.2%). The majority of clinicians had been in practice 11–20 years (34.5%) and in academic practice settings (65.5%). Prescribing practices More respondents had prescribed vismodegib ( n = 18, 66.7%) than sonidegib ( n = 11, 47.7%). Many vismodegib prescribers had over 10 years of experience prescribing vismodegib (38.9%, and 33.3% had 5–10 years of experience. Of those who had prescribed sonidegib, 36.4% had prescribed it 1–2 years, 18.2% for 3–5 years, 36.4% for 5–10 years, and 9.1% for 10 + years. All providers who prescribed sonidegib had also prescribed vismodegib. Reported prescribing habits favored vismodegib, with 54.5% of clinicians primarily prescribing vismodegib, 36.4% preferring sonidegib, and only 9.1% endorsing prescribing both equally. Physicians were more likely to switch from vismodegib to sonidegib if experiencing tolerability issues ( n = 7/11, 36.6%) rather than sonidegib to vismodegib ( n = 1/11, 9.1%). Adverse Effects and Tolerability Dysgeusia was the most common distressing AE to patients for vismodegib (55.6%) and Sonidegib (63.6%). 33.4% of providers had to stop administration of vismodegib due to severity of AE in 50% or more of patients. In contrast, no providers indicated that they had to stop administration in 50% or more of their patients due to AE severity with sonidegib. AE was the most common reason patients had to be taken off both vismodegib ( n = 11/18, 61.1%) and sonidegib ( n = 6/11, 55.4%). Financial accessibility and insurance coverage were commonly cited causes to stop vismodegib ( n = 2/11, 11.1%) and sonidegib ( n = 2/11 = 18.2%), in addition to tumor progression (vismodegib: n = 5/11, 27.8%; sonidegib: n = 2/11 = 18.2%). Off-label Dosing 41.9% ( n = 10/18) of respondents endorsed using off-label dosing with either SMOi. There was a wide variety in approach, but the most common was 1 month on, 1 month off dosing. 40.0% of respondents reported using off-label dosing strategies in > 75% of their patients, and 30% used off-label approaches in only 1–10%, underscoring significant variability in clinical practice. Preferences and beliefs 58.3% of respondents indicated they believed that vismodegib and sonidegib are similar therapeutic options for laBCC and mBCC, while 20.8% were not sure which therapeutic option they believe to be better. 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 12.4% chose vismodegib. Respondents had varying accuracy when asked to identify key differences in SMOi mechanisms and outcomes, such as which drug takes longer to achieve steady state, or which has higher median progression free survival (Table I). Discussion Clinical decision-making and adjustments involved in prescribing SMOi for advanced BCC is nuanced. Findings from our survey suggest a prescribing preference for vismodegib despite providers believing them to be comparable medication options, if not superior tolerability in sonidegib. Although vismodegib was prescribed more frequently, the data from ERIVANCE and BOLT, when compared with modified criteria, suggest a comparable, if not inferior, tolerability and AE profile compared to sonidegib [7]. As expected, AEs were the most difficult aspect of managing SMOi. Clinicians were more inclined to switch from vismodegib to sonidegib when AEs were problematic, which could indicate a perceived advantage in tolerability for sonidegib. The clinical decision to switch from vismodegib to sonidegib is supported by prior and original pivotal trial studies. Vismodegib had a notably high rate of 98% of patients experiencing AE in the STEVIE trial [2]. In comparison, analysis of sonidegib in BOLT revealed that only 43% of patients in the 200 mg group experienced AEs [5]. Studies have demonstrated successful reductions in AE when switching from vismodegib to sonidegib, although there is potential that the benefit arises from the drug holiday, rather than from the other SMOi [6]. Relatedly, our study highlighted clinicians’ strategies to implement various dosing regimens, including 1 month on, 1 month off; 2 weeks on, 2 weeks off; and every other day. Alternative dosing has been studied with success with vismodegib regarding improved tolerability and is also utilized in clinical practice for sonidegib [3,12]. Over two-thirds of respondents in this study believed that the two medications had the same incidence of AEs or did not know which medication had higher incidence (Table I). Given that AE are the most common reason for discontinuation and have major implications on treatment outcomes and patient quality of life, dermatologists’ familiarity with these drug profiles is crucial [8]. Emerging data have strongly reflected higher tolerability of sonidegib. The CARADERM real-world trial demonstrated significantly lower cumulative incidence of AE, severity of AE, and notably high discontinuation rates due to clinical benefit at 12 months, rather than AE (50% vs 30%) [1, 9]. Data from landmark trials are important, though they provide challenges for clinical interpretation. Clinician discrepancies in knowledge were evidenced in our findings regarding accurate knowledge of the pharmacokinetic profiles, median duration of response, and median progression-free survival between vismodegib and sonidegib. As immunotherapies are becoming relied upon for advanced BCC treatment in the refractory or intolerability setting, increasing provider education about the differences in SMOi medications will be critical to balancing therapeutics with tolerability, as well as potentially utilizing them earlier or in a wider range of clinical scenarios. Results of prescribing preferences of these experts in multiple fields highlight the lack of familiarity and uniformity 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. Although sample size was limited, insights from this study underscore the importance of personalized treatment strategies and considering patient-specific tolerability. Clinically, this data supports the need for a flexible approach to SMOi therapy and the importance of utilizing findings from real-world practice into clinical guidelines. Physician education will be critical in aligning physicians’ real-world use of SMOi with landmark and emerging clinical data. Declarations Conflicts of interest : Dr. Schlesinger has served as an advisor, investigator, and consultant for AbbVie, Allergan (an AbbVie Company), Almirall, Amgen, Alumis, Apogee, Arcutis, ASLAN, Benev, Biofrontera, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Dermsquared, Eli Lilly and Company, ExoCoBio, Flint Clinical, Galderma, Genentech, Highlightll, HTL Biotechnologies, Incyte, Janssen, L’Oreal, Novartis, Pfizer Inc., RBC Consultants, Regeneron, Rion, Sanofi, SiSaf, Sun Pharma, Takeda, UCB, and Verrica, and has received a salary from Avant-Health. Board of Advisers for Chronicle Medical Software. Dr. Chang has been a consultant and clinical investigator for Sun Pharma. Dr. Chang's spouse is an employee of Amgen. Dr. Farberg is an Advisor/Consultant/Research for Regeneron, Sun Pharma. Funding : None IRB : NCR235400 Exempt status References Basset-Seguin N, Djermane M, Herms F, et al. Effectiveness, safety and reasons for discontinuation of sonidegib for patients with locally advanced basal cell carcinoma: A real-word evidence analysis from the French national registry CARADERM. Journal of the European Academy of Dermatology and Venereology. 2025;39(7):e589-e591. https://doi.org/10.1111/jdv.20496 Basset-Séguin N, Hauschild A, Kunstfeld R, et al. Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial. European Journal of Cancer. 2017;86:334-348. https://doi.org/10.1016/j.ejca.2017.08.022 Dréno B, Kunstfeld R, Hauschild A, et al. Two intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas (MIKIE): a randomised, regimen-controlled, double-blind, phase 2 trial. The Lancet Oncology. 2017;18(3):404-412. https://doi.org/10.1016/S1470-2045(17)30072-4 Dummer R, Ascierto PA, Basset‐Seguin N, et al. Sonidegib and vismodegib in the treatment of patients with locally advanced basal cell carcinoma: a joint expert opinion. Journal of the European Academy of Dermatology and Venereology. 2020;34(9):1944-1956. https://doi.org/10.1111/jdv.16230 Dummer R, Guminksi A, Gutzmer R, et al. Long‐term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42‐month analysis of the phase II randomized, double‐blind BOLT study. British Journal of Dermatology. 2019;182(6):1369-1378. https://doi.org/10.1111/bjd.18552 Farberg AS, Portela D, Sharma D, Meenal Kheterpal. Evaluation of the Tolerability of Hedgehog Pathway Inhibitors in the Treatment of Advanced Basal Cell Carcinoma: A Narrative Review of Treatment Strategies. American Journal of Clinical Dermatology. 2024;25(5):779-794. https://doi.org/10.1007/s40257-024-00870-3 Gutzmer R, Robert C, Loquai C, et al. Assessment of various efficacy outcomes using ERIVANCE-like criteria in patients with locally advanced basal cell carcinoma receiving sonidegib: results from a preplanned sensitivity analysis. BMC Cancer. 2021;21(1):1244. https://doi.org/10.1186/s12885-021-08968-1 Hansson J, Bartley K, Karagiannis T, et al. Assessment of quality of life using Skindex-16 in patients with advanced basal cell carcinoma treated with vismodegib in the STEVIE study. European Journal of Dermatology. 2018;28(6):775-783. https://doi.org/10.1684/ejd.2018.3448 Herms F, Mourad Djermane, Beylot-Barry M, et al. Comparison of the tolerability and safety of hedgehog inhibitors in real-life: A cohort of 330 patients with locally advanced basal cell carcinoma. Journal of Clinical Oncology. 2025;43(16_suppl):9583-9583. https://doi.org/10.1200/jco.2025.43.16_suppl.9583 Migden MR, Guminski A, Gutzmer R, et al. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. The Lancet Oncology. 2015;16(6):716-728. https://doi.org/10.1016/s1470-2045(15)70100-2 Sekulic A, Migden MR, Oro AE, et al. Efficacy and Safety of Vismodegib in Advanced Basal-Cell Carcinoma. New England Journal of Medicine . 2012;366(23):2171-2179. https://doi.org/10.1056/nejmoa1113713 Yang K, Ho-Pham H, Pieper C, Huang CC, Bergman DJ. Alternate Dosing Regimens for Vismodegib: A Literature Review. Current Treatment Options in Oncology . 2025;26(7):587-591. https://doi.org/10.1007/s11864-025-01332-6 Table 1 Table I. Responses to Questions Assessing Knowledge of Clinical Trials. Correct answer to each question marked with an asterisk (*). Questions Answer Options Responses % (n) Chi-square analysis Which drug do you believe takes longer to achieve a steady state? Vismodegib 12.5 (3) χ²=4.33, df = 3, p = 0.228 Sonidegib* 20.8 (5) They take the same time to achieve steady state 25 (6) I don’t know 41.7 (10) Supportive data and label approval for every other day dosing exists for which drug(s)? Vismodegib 20.8 (5) χ²=5.58, df = 4, p = 0.233 Sonidegib 16.7 (4) Both 4.2 (1) Neither* 25 (6) I don't know 33.3 (8) Which drug do you believe has a higher median duration of response in the registrational clinical trials? Vismodegib 8.3 (2) χ²=4.33, df = 3, p = 0.228 Sonidegib* 25 (6) They have the same median duration of response 29.2 (7) I don’t know 37.5 (9) Which drug do you believe has a higher median progression-free survival in the registrational clinical trials? Vismodegib 4.2 (1) χ²=7.0, df = 3, p = 0.072 Sonidegib* 25 (6) They have the same median progression-free survival 29.2 (7) I don’t know 41.7 (10) Which drug do you believe has a higher incidence of adverse effects in the registrational clinical trials? Vismodegib* 33.3 (8) χ²=0, df = 2, p = 1.0 Sonidegib 0 (0) They have the same incidence of adverse effects 33.3 (8) I don't know 33.3 (8) P-value was determined using the chi-square goodness of fit test. Additional Declarations Competing interest reported. Dr. Schlesinger has served as an advisor, investigator, and consultant for AbbVie, Allergan (an AbbVie Company), Almirall, Amgen, Alumis, Apogee, Arcutis, ASLAN, Benev, Biofrontera, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Dermsquared, Eli Lilly and Company, ExoCoBio, Flint Clinical, Galderma, Genentech, Highlightll, HTL Biotechnologies, Incyte, Janssen, L’Oreal, Novartis, Pfizer Inc., RBC Consultants, Regeneron, Rion, Sanofi, SiSaf, Sun Pharma, Takeda, UCB, and Verrica, and has received a salary from Avant-Health. Board of Advisers for Chronicle Medical Software. Dr. Chang has been a consultant and clinical investigator for Sun Pharma. Dr. Chang's spouse is an employee of Amgen. Dr. Farberg is an Advisor/Consultant/Research for Regeneron, Sun Pharma. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 02 Feb, 2026 Reviewers agreed at journal 25 Jan, 2026 Reviewers agreed at journal 24 Jan, 2026 Reviewers invited by journal 11 Nov, 2025 Editor assigned by journal 17 Sep, 2025 Submission checks completed at journal 17 Sep, 2025 First submitted to journal 15 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7623555","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Short Report","associatedPublications":[],"authors":[{"id":546544493,"identity":"0cdaa8e4-2170-443c-9146-f6b18d511d2e","order_by":0,"name":"Kennedy H. 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Dr. Schlesinger has served as an advisor, investigator, and consultant for AbbVie, Allergan (an AbbVie Company), Almirall, Amgen, Alumis, Apogee, Arcutis, ASLAN, Benev, Biofrontera, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Dermsquared, Eli Lilly and Company, ExoCoBio, Flint Clinical, Galderma, Genentech, Highlightll, HTL Biotechnologies, Incyte, Janssen, L’Oreal, Novartis, Pfizer Inc., RBC Consultants, Regeneron, Rion, Sanofi, SiSaf, Sun Pharma, Takeda, UCB, and Verrica, and has received a salary from Avant-Health. Board of Advisers for Chronicle Medical Software. Dr. Chang has been a consultant and clinical investigator for Sun Pharma. Dr. Chang's spouse is an employee of Amgen. Dr. Farberg is an Advisor/Consultant/Research for Regeneron, Sun Pharma.","formattedTitle":"Comparison of Smoothened Inhibitors in Treating Basal Cell Carcinoma: A Survey Study of Multidisciplinary Expert Opinions and Clinical Experiences","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSmoothened inhibitors (SMOi), also known as hedgehog inhibitors (HHI), are a targeted therapy that have transformed the treatment landscape for locally advanced BCC (laBCC) and metastatic BCC (mBCC). Landmark studies, ERIVANCE for vismodegib and BOLT for sonidegib, provided valuable insights into SMOi efficacy, dosing, adverse effects (AE), and pharmacokinetics [10,11]. Both drugs are administered orally once daily (vismodegib 150 mg, sonidegib 200 mg), but sonidegib requires fasting administration, has a longer elimination half-life (28-30 days vs. 4-12 days), and a larger volume of distribution. Muscle spasms, alopecia, and dysgeusia comprise some of the common, shared AE. [4] However, differences in study criteria and methods have caused variability in treatment utilization and require nuanced clinical interpretation. Additionally, while SMOi are effective, their use is often limited by AE [4].\u0026nbsp;\u003c/p\u003e\n"},{"header":"Methods","content":"\u003cp\u003eA 35-item anonymous REDCap survey was released in Spring 2024 via email to the Skin Cancer Outcomes Consortium. Information was collected regarding clinical practice setting, extent of experience treating advanced BCC with SMOi, comparisons of experiences with tolerability and AE, and preferences between these two FDA-approved options.\u003c/p\u003e\n"},{"header":"Results","content":"\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e\u003ch2\u003eRespondent demographics\u003c/h2\u003e\u003cp\u003e29 clinicians who treat laBCC and mBCC in various fields within the United States responded (Dermatology 27.6%, Mohs surgeon 13.8%, Medical Oncologist 34.5%, Surgical Oncologist 10.3%, Other 6.9%, Head and Neck Surgeon 3.4%, Radiation Oncologist 3.4%) (response rate: 37.2%). The majority of clinicians had been in practice 11\u0026ndash;20 years (34.5%) and in academic practice settings (65.5%).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePrescribing practices\u003c/h2\u003e\u003cp\u003eMore respondents had prescribed vismodegib (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;18, 66.7%) than sonidegib (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;11, 47.7%). Many vismodegib prescribers had over 10 years of experience prescribing vismodegib (38.9%, and 33.3% had 5\u0026ndash;10 years of experience. Of those who had prescribed sonidegib, 36.4% had prescribed it 1\u0026ndash;2 years, 18.2% for 3\u0026ndash;5 years, 36.4% for 5\u0026ndash;10 years, and 9.1% for 10\u0026thinsp;+\u0026thinsp;years. All providers who prescribed sonidegib had also prescribed vismodegib. Reported prescribing habits favored vismodegib, with 54.5% of clinicians primarily prescribing vismodegib, 36.4% preferring sonidegib, and only 9.1% endorsing prescribing both equally. Physicians were more likely to switch from vismodegib to sonidegib if experiencing tolerability issues (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;7/11, 36.6%) rather than sonidegib to vismodegib (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1/11, 9.1%).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eAdverse Effects and Tolerability\u003c/h3\u003e\n\u003cp\u003eDysgeusia was the most common distressing AE to patients for vismodegib (55.6%) and Sonidegib (63.6%). 33.4% of providers had to stop administration of vismodegib due to severity of AE in 50% or more of patients. In contrast, no providers indicated that they had to stop administration in 50% or more of their patients due to AE severity with sonidegib. AE was the most common reason patients had to be taken off both vismodegib (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;11/18, 61.1%) and sonidegib (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;6/11, 55.4%). Financial accessibility and insurance coverage were commonly cited causes to stop vismodegib (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2/11, 11.1%) and sonidegib (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2/11\u0026thinsp;=\u0026thinsp;18.2%), in addition to tumor progression (vismodegib: \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;5/11, 27.8%; sonidegib: \u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;2/11\u0026thinsp;=\u0026thinsp;18.2%).\u003c/p\u003e\n\u003ch3\u003eOff-label Dosing\u003c/h3\u003e\n\u003cp\u003e41.9% (\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;10/18) of respondents endorsed using off-label dosing with either SMOi. There was a wide variety in approach, but the most common was 1 month on, 1 month off dosing. 40.0% of respondents reported using off-label dosing strategies in \u0026gt;\u0026thinsp;75% of their patients, and 30% used off-label approaches in only 1\u0026ndash;10%, underscoring significant variability in clinical practice.\u003c/p\u003e\n\u003ch3\u003ePreferences and beliefs\u003c/h3\u003e\n\u003cp\u003e58.3% of respondents indicated they believed that vismodegib and sonidegib are similar therapeutic options for laBCC and mBCC, while 20.8% were not sure which therapeutic option they believe to be better. 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, \u0026ldquo;All things considered, which drug do you believe is superior for treating locally advanced BCC?\u0026rdquo; 41.7% responded that they believed them to be similar, 25% said \u0026lsquo;I don\u0026rsquo;t know\u0026rsquo;, 20.8% chose sonidegib, and 12.4% chose vismodegib. Respondents had varying accuracy when asked to identify key differences in SMOi mechanisms and outcomes, such as which drug takes longer to achieve steady state, or which has higher median progression free survival (Table I).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eClinical decision-making and adjustments involved in prescribing SMOi for advanced BCC is nuanced. Findings from our survey suggest a prescribing preference for vismodegib despite providers believing them to be comparable medication options, if not superior tolerability in sonidegib. Although vismodegib was prescribed more frequently, the data from ERIVANCE and BOLT, when compared with modified criteria, suggest a comparable, if not inferior, tolerability and AE profile compared to sonidegib [7].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;As expected, AEs were the most difficult aspect of managing SMOi. Clinicians were more inclined to switch from vismodegib to sonidegib when AEs were problematic, which could indicate a perceived advantage in tolerability for sonidegib. The clinical decision to switch from vismodegib to sonidegib is supported by prior and original pivotal trial studies. Vismodegib had a notably high rate of 98% of patients experiencing AE in the STEVIE trial [2]. In comparison, analysis of sonidegib in BOLT revealed that only 43% of patients in the 200 mg group experienced AEs [5]. Studies have demonstrated successful reductions in AE when switching from vismodegib to sonidegib, although there is potential that the benefit arises from the drug holiday, rather than from the other SMOi [6]. Relatedly, our study highlighted clinicians\u0026rsquo; strategies to implement various dosing regimens, including 1 month on, 1 month off; 2 weeks on, 2 weeks off; and every other day. Alternative dosing has been studied with success with vismodegib regarding improved tolerability and is also utilized in clinical practice for sonidegib [3,12].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Over two-thirds of respondents in this study believed that the two medications had the same incidence of AEs or did not know which medication had higher incidence (Table I). Given that AE are the most common reason for discontinuation and have major implications on treatment outcomes and patient quality of life, dermatologists\u0026rsquo; familiarity with these drug profiles is crucial [8]. Emerging data have strongly reflected higher tolerability of sonidegib. The CARADERM real-world trial demonstrated significantly lower cumulative incidence of AE, severity of AE, and notably high discontinuation rates due to clinical benefit at 12 months, rather than AE (50% vs 30%) [1, 9].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Data from landmark trials are important, though they provide challenges for clinical interpretation. Clinician discrepancies in knowledge were evidenced in our findings regarding accurate knowledge of the pharmacokinetic profiles, median duration of response, and median progression-free survival between vismodegib and sonidegib. As immunotherapies are becoming relied upon for advanced BCC treatment in the refractory or intolerability setting, increasing provider education about the differences in SMOi medications will be critical to balancing therapeutics with tolerability, as well as potentially utilizing them earlier or in a wider range of clinical scenarios.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Results of prescribing preferences of these experts in multiple fields highlight the lack of familiarity and uniformity 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. Although sample size was limited, insights from this study underscore the importance of personalized treatment strategies and considering patient-specific tolerability. Clinically, this data supports the need for a flexible approach to SMOi therapy and the importance of utilizing findings from real-world practice into clinical guidelines. Physician education will be critical in aligning physicians\u0026rsquo; real-world use of SMOi with landmark and emerging clinical data.\u003c/p\u003e"},{"header":"Declarations","content":"\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e: \u003cstrong\u003eDr. Schlesinger\u0026nbsp;\u003c/strong\u003ehas served as an advisor, investigator, and consultant for AbbVie, Allergan (an AbbVie Company), Almirall, Amgen, Alumis, Apogee, Arcutis, ASLAN, Benev, Biofrontera, Boehringer Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Dermsquared, Eli Lilly and Company, ExoCoBio, Flint Clinical, Galderma, Genentech, Highlightll, HTL Biotechnologies, Incyte, Janssen, L\u0026rsquo;Oreal, Novartis, Pfizer Inc., RBC Consultants, Regeneron, Rion, Sanofi, SiSaf, Sun Pharma, Takeda, UCB, and Verrica, and has received a salary from Avant-Health. Board of Advisers for Chronicle Medical Software. \u003cstrong\u003eDr. Chang\u003c/strong\u003e has been a consultant and clinical investigator for Sun Pharma. Dr. Chang\u0026apos;s spouse is an employee of Amgen. \u003cstrong\u003eDr. Farberg\u003c/strong\u003e is an Advisor/Consultant/Research for Regeneron, Sun Pharma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIRB\u003c/strong\u003e: NCR235400 Exempt status\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBasset-Seguin N, Djermane M, Herms F, et al. Effectiveness, safety and reasons for discontinuation of sonidegib for patients with locally advanced basal cell carcinoma: A real-word evidence analysis from the French national registry CARADERM. \u003cem\u003eJournal of the European Academy of Dermatology and Venereology. \u003c/em\u003e2025;39(7):e589-e591. https://doi.org/10.1111/jdv.20496\u003c/li\u003e\n\u003cli\u003eBasset-S\u0026eacute;guin N, Hauschild A, Kunstfeld R, et al. Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial.\u003cem\u003e European Journal of Cancer. \u003c/em\u003e2017;86:334-348. https://doi.org/10.1016/j.ejca.2017.08.022\u003c/li\u003e\n\u003cli\u003eDr\u0026eacute;no B, Kunstfeld R, Hauschild A, et al. Two intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas (MIKIE): a randomised, regimen-controlled, double-blind, phase 2 trial. \u003cem\u003eThe Lancet Oncology.\u003c/em\u003e 2017;18(3):404-412. https://doi.org/10.1016/S1470-2045(17)30072-4\u003c/li\u003e\n\u003cli\u003eDummer R, Ascierto PA, Basset‐Seguin N, et al. Sonidegib and vismodegib in the treatment of patients with locally advanced basal cell carcinoma: a joint expert opinion. \u003cem\u003eJournal of the European Academy of Dermatology and Venereology.\u003c/em\u003e 2020;34(9):1944-1956. https://doi.org/10.1111/jdv.16230\u003c/li\u003e\n\u003cli\u003eDummer R, Guminksi A, Gutzmer R, et al. Long‐term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42‐month analysis of the phase II randomized, double‐blind BOLT study. \u003cem\u003eBritish Journal of Dermatology.\u003c/em\u003e 2019;182(6):1369-1378. https://doi.org/10.1111/bjd.18552\u003c/li\u003e\n\u003cli\u003eFarberg AS, Portela D, Sharma D, Meenal Kheterpal. Evaluation of the Tolerability of Hedgehog Pathway Inhibitors in the Treatment of Advanced Basal Cell Carcinoma: A Narrative Review of Treatment Strategies. \u003cem\u003eAmerican Journal of Clinical Dermatology.\u003c/em\u003e 2024;25(5):779-794. https://doi.org/10.1007/s40257-024-00870-3\u003c/li\u003e\n\u003cli\u003eGutzmer R, Robert C, Loquai C, et al. Assessment of various efficacy outcomes using ERIVANCE-like criteria in patients with locally advanced basal cell carcinoma receiving sonidegib: results from a preplanned sensitivity analysis. \u003cem\u003eBMC Cancer. \u003c/em\u003e2021;21(1):1244. https://doi.org/10.1186/s12885-021-08968-1\u003c/li\u003e\n\u003cli\u003eHansson J, Bartley K, Karagiannis T, et al. Assessment of quality of life using Skindex-16 in patients with advanced basal cell carcinoma treated with vismodegib in the STEVIE study. \u003cem\u003eEuropean Journal of Dermatology. \u003c/em\u003e2018;28(6):775-783. https://doi.org/10.1684/ejd.2018.3448\u003c/li\u003e\n\u003cli\u003eHerms F, Mourad Djermane, Beylot-Barry M, et al. Comparison of the tolerability and safety of hedgehog inhibitors in real-life: A cohort of 330 patients with locally advanced basal cell carcinoma. \u003cem\u003eJournal of Clinical Oncology.\u003c/em\u003e 2025;43(16_suppl):9583-9583. https://doi.org/10.1200/jco.2025.43.16_suppl.9583\u003c/li\u003e\n\u003cli\u003eMigden MR, Guminski A, Gutzmer R, et al. Treatment with two different doses of sonidegib in patients with locally advanced or metastatic basal cell carcinoma (BOLT): a multicentre, randomised, double-blind phase 2 trial. \u003cem\u003eThe Lancet Oncology.\u003c/em\u003e 2015;16(6):716-728. https://doi.org/10.1016/s1470-2045(15)70100-2\u003c/li\u003e\n\u003cli\u003eSekulic A, Migden MR, Oro AE, et al. Efficacy and Safety of Vismodegib in Advanced Basal-Cell Carcinoma. \u003cem\u003eNew England Journal of Medicine\u003c/em\u003e. 2012;366(23):2171-2179. https://doi.org/10.1056/nejmoa1113713\u003c/li\u003e\n\u003cli\u003eYang K, Ho-Pham H, Pieper C, Huang CC, Bergman DJ. Alternate Dosing Regimens for Vismodegib: A Literature Review. \u003cem\u003eCurrent Treatment Options in Oncology\u003c/em\u003e. 2025;26(7):587-591. https://doi.org/10.1007/s11864-025-01332-6\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 1","content":"\u003cp\u003eTable I. Responses to Questions Assessing Knowledge of Clinical Trials. Correct answer to each question marked with an asterisk (*).\u0026nbsp;\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"623\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eQuestions\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnswer Options\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eResponses % (n)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 103px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eChi-square analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWhich drug do you believe takes longer to achieve a steady state?\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eVismodegib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e12.5 \u0026nbsp;(3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026chi;\u0026sup2;=4.33, df = 3, p = 0.228\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eSonidegib*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e20.8 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eThey take the same time to achieve steady state\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e25 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eI don\u0026rsquo;t know\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e41.7 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"5\" style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSupportive data and label approval for every other day dosing exists for which drug(s)?\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eVismodegib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e20.8 (5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"5\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026chi;\u0026sup2;=5.58, df = 4, p = 0.233\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eSonidegib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e16.7 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eBoth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e4.2 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eNeither*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e25 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eI don\u0026apos;t know\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e33.3 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWhich drug do you believe has a higher median duration of response in the registrational clinical trials?\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eVismodegib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e8.3 (2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026chi;\u0026sup2;=4.33, df = 3, p = 0.228\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eSonidegib*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e25 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eThey have the same median duration of response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e29.2 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eI don\u0026rsquo;t know\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e37.5 (9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWhich drug do you believe has a higher median progression-free survival in the registrational clinical trials?\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eVismodegib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e4.2 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026chi;\u0026sup2;=7.0, df = 3, p = 0.072\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eSonidegib*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e25 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eThey have the same median progression-free survival\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e29.2 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eI don\u0026rsquo;t know\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e41.7 (10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWhich drug do you believe has a higher incidence of adverse effects in the registrational clinical trials?\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eVismodegib*\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e33.3 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"4\" style=\"width: 103px;\"\u003e\n \u003cp\u003e\u0026chi;\u0026sup2;=0, df = 2, p = 1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eSonidegib\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e0 (0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eThey have the same incidence of adverse effects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e33.3 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 225px;\"\u003e\n \u003cp\u003eI don\u0026apos;t know\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 135px;\"\u003e\n \u003cp\u003e33.3 (8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eP-value was determined using the chi-square goodness of fit test.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"basal cell carcinoma, BCC, laBCC, mBCC, smoothened inhibitors, SMOi, hedgehog inhibitors, HHI, vismodegib, sonidegib","lastPublishedDoi":"10.21203/rs.3.rs-7623555/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7623555/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSmoothened 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.\u003c/p\u003e","manuscriptTitle":"Comparison of Smoothened Inhibitors in Treating Basal Cell Carcinoma: A Survey Study of Multidisciplinary Expert Opinions and Clinical Experiences","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-21 12:43:16","doi":"10.21203/rs.3.rs-7623555/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-02-02T18:39:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"229857264649549627459495850619181570749","date":"2026-01-26T02:23:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"182349476063214703524480044197858902127","date":"2026-01-24T16:40:01+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-11T21:28:05+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-17T07:21:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-17T07:20:58+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Dermatological Research","date":"2025-09-15T18:45:44+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"6abbb34e-91fb-443b-a6b1-8717214b834e","owner":[],"postedDate":"November 21st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-21T12:43:16+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-21 12:43:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7623555","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7623555","identity":"rs-7623555","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}