How Dermatologists Use Hedgehog Inhibitors for Locally Advanced BCC

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, Todd Schlesinger, MD, reviews key findings from the 2025 Dermatology Online Journal expert consensus panel, addressing safety, efficacy, and administration of HHIs with a focus on real-world clinical application.

Reducing tumor burden with HHIs as primary or neoadjuvant therapy

Consensus Statement 1 
HHIs are an effective treatment that can help reduce the tumor burden of locally advanced basal cell carcinomas as a primary or neoadjuvant therapy prior to Mohs or other interventions.

Dr Schlesinger emphasizes that HHIs play an important role in reducing tumor burden in patients with large, locally advanced, or recurrent basal cell carcinomas. These therapies may be used as primary systemic treatment in patients who are not surgical candidates, as well as in the neoadjuvant setting to shrink tumors prior to Mohs surgery or other interventions.

He notes that patients with tumors involving critical structures, such as the eye, ear, or nose, may particularly benefit from a neoadjuvant approach, where tumor reduction can improve surgical feasibility and outcomes.

Identifying appropriate patients for sonidegib

Consensus Statement 2 
Sonidegib can be considered for patients with locally advanced basal cell carcinoma that has recurred following surgery or radiation, individuals who are not good candidates for surgery or radiation, and/or patients with high burdens of BCCs including those with Gorlin syndrome.

Building on this statement, Dr Schlesinger describes a broad group of patients who may be appropriate candidates for Hedgehog pathway inhibition. These include individuals with large or locally advanced tumors, patients with recurrent disease, and those who are not candidates for, or who decline, surgery or radiation.

Sonidegib may be used either as a primary systemic therapy or in the neoadjuvant setting, depending on clinical context and patient goals.

Dosing considerations and maintaining patients on therapy

Consensus Statement 3 
It is recommended that 200 mg of sonidegib be taken daily, and duration and dose can be adjusted according to patient response and side effects.

Dr Schlesinger explains that dosing is one of the most important considerations when initiating HHIs. Sonidegib is dosed at 200 mg once daily for the management of laBCC, and clinicians should proactively address tolerability from the outset.

Supportive measures such as ensuring adequate hydration and nutrition can help mitigate adverse events. He also notes that supplements such as L-carnitine may help stabilize muscle mitochondria and reduce the risk of muscle-related adverse events, including cramping. The overarching goal is to keep patients on therapy as long as possible while maintaining quality of life.

Managing common adverse effects with flexibility

Consensus Statement 4 
The most common side effects associated with the use of Hedgehog inhibitors include muscle cramps/spasms, alopecia, taste alterations, and fatigue.

Dr Schlesinger notes that while these adverse effects are common, they are often manageable. In cases where side effects become problematic, such as with muscle cramps, myalgias, alopecia, or headaches, dose adjustments may be appropriate.

He describes the use of intermittent dosing strategies and notes that in his clinical experience, patients can maintain meaningful efficacy even at reduced dosing frequencies; this can improve tolerability and encourage patients to remain on therapy longer.

Why expert consensus matters in advanced skin cancer care

In closing, Dr Schlesinger reflects on the importance of expert consensus statements and the modified Delphi process, particularly in disease areas where there is no single, well-defined standard of care. Consensus recommendations developed by clinicians experienced in managing advanced skin cancers help define best practices and provide practical guidance for dermatologists as new therapies enter clinical use.

He encourages colleagues to stay engaged with emerging consensus publications, participate when possible, and incorporate these statements into practice to support thoughtful, evidence-informed patient care.

Key takeaways

• HHIs are effective options for reducing tumor burden in laBCC
• Sonidegib may be used as primary systemic therapy or in the neoadjuvant setting, depending on patient factors
• Standard dosing is 200 mg daily, with flexibility to adjust based on response and tolerability
• Common adverse effects are manageable and may be addressed through supportive care and intermittent dosing strategies
• Expert consensus statements provide valuable guidance when standards of care are evolving or not clearly defined