Strengthening Confidence in Hedgehog Inhibitors for Locally Advanced Basal Cell Carcinoma

This video is sponsored by Sun Pharma. Its content is editorially independent of the sponsor.

This expert video series is designed to support dermatologist confidence in the use of Hedgehog inhibitors (HHIs) for the management of locally advanced basal cell carcinoma (laBCC). In this segment, Shannon Trotter, DO, reviews key findings from the 2025 Journal of Drugs in Dermatology (JDD) expert consensus panel, addressing common questions around patient selection, efficacy, safety, and practical differences between the two available HHIs, vismodegib and sonidegib.

With two HHIs now available, dermatologists are increasingly tasked with distinguishing how these agents compare, when to use them, and how to counsel patients effectively. Dr Trotter walks through three foundational consensus statements to help guide real-world decision-making.

Defining locally advanced BCC: why consensus matters

Before reviewing treatment guidance, Dr Trotter notes that there is no single, universally accepted definition of laBCC. Disease classification often reflects a combination of tumor-related and patient-related factors, including tumor size, anatomic location (particularly high-function or cosmetically sensitive areas such as the eyelids, nose, ears, and lips), aggressive histologic subtypes, and patient suitability for surgery or radiation. This variability underscores the need for consensus-driven guidance to support consistent and confident care.

Consensus statement 1

Basal cell carcinoma surgery can lead to aesthetic and functional morbidity when tumors are in anatomically sensitive areas or large size. Hedgehog inhibitors can be used to decrease the size of tumors prior to surgery or as a primary treatment so that surgical outcomes are functionally and aesthetically optimized.

Dr Trotter emphasizes that many patients present with BCC in locations where surgery may result in significant functional impairment or cosmetic morbidity. In these cases, HHIs can be used neoadjuvantly to shrink tumors prior to surgery or as primary therapy when surgery is not optimal.

Clinical trials of both approved HHIs have demonstrated meaningful and durable responses in laBCC. Although there are no head-to-head trials comparing vismodegib and sonidegib, analyses using comparable RECIST criteria show similar complete response rates. These data support the use of HHIs not only as adjuncts to surgery, but also as effective primary treatment options for appropriately selected patients.

Consensus statement 2

Patients should be counseled about the most common potential side effects of alopecia, taste alterations, and muscle spasms. Other less common adverse events include but are not limited to, gastrointestinal disorders.

Historically, tolerability has been a major reason for treatment interruption or discontinuation with HHIs. Dr Trotter stresses the importance of early, proactive counseling to improve adherence. The most common adverse effects include alopecia, dysgeusia, muscle spasms, and fatigue, and patients benefit from understanding not only what to expect, but when side effects are likely to occur.

She explains that differences in molecular structure contribute to variation in side effect onset between agents, with vismodegib typically associated with earlier onset and sonidegib with later onset. Practical mitigation strategies may include preventive or early interventions for muscle cramps, dietary counseling for taste changes, and discussion of options for alopecia. Setting expectations and distinguishing between preventable versus manageable effects can meaningfully improve persistence with therapy.

Consensus statement 3

Sonidegib is associated with a lower rate of and longer median time to onset of adverse effects than vismodegib.

Dr Trotter reviews data showing that sonidegib is associated with lower rates of muscle spasms, dysgeusia, and alopecia, as well as a longer median time to onset of these adverse effects compared with vismodegib. These differences are attributed to distinct pharmacokinetic and molecular properties.

Clinically, this matters when tailoring therapy. Patients doing well on vismodegib may continue treatment, while those struggling with tolerability may benefit from switching to sonidegib. Understanding these distinctions allows dermatologists to individualize therapy rather than abandoning HHI treatment altogether.

Key takeaways

• Locally advanced BCC lacks a single definition, making consensus-driven guidance essential
• Hedgehog inhibitors can be used as neoadjuvant or primary therapy to optimize functional and aesthetic outcomes
• Both approved HHIs demonstrate meaningful and durable efficacy in laBCC
• Early, proactive counseling on side effects improves adherence and persistence
• Sonidegib is associated with lower rates and delayed onset of common adverse effects compared with vismodegib
• Understanding practical differences between HHIs supports individualized, patient-centered treatment decisions

For additional consensus statements and deeper discussion, clinicians are encouraged to review the full 2025 JDD consensus publication.