Experts Discuss Hedgehog Inhibitor Selection in Advanced BCC

As treatment options for advanced basal cell carcinoma (BCC) continue to evolve, dermatologists face important decisions regarding surgical candidacy, systemic therapy selection, and adverse-effect management. Although hedgehog pathway inhibitors (HHIs) have expanded nonsurgical treatment options, differences in clinical experience, treatment tolerability, and patient preferences continue to influence prescribing practices.

During a November 5, 2026, Dermatology Times Case-Based Roundtable in San Diego, California, Vishal A. Patel, MD, FASDS, FACMS, associate professor of dermatology and hematology/oncology at The George Washington University School of Medicine and Health Sciences and director of the Cutaneous Oncology Program at The George Washington University Cancer Center, led a discussion titled "Differentiating Hedgehog Pathway Inhibitors in Advanced Basal Cell Carcinoma."

Through interactive polling and clinical case scenarios, participants explored the practical considerations involved in selecting between vismodegib and sonidegib, managing treatment-related adverse effects, and identifying patients who may benefit from systemic treatment.

Rethinking Surgical Candidacy in Advanced BCC

The discussion began by examining how clinicians define locally advanced and difficult-to-treat BCC, particularly when surgical intervention may result in significant functional or cosmetic consequences.

Participants considered tumor location, size, depth of invasion, and the potential need for complex reconstruction when determining treatment approaches. Although surgery remains a central component of BCC management, panelists acknowledged that technical resectability does not always translate to an optimal treatment strategy.

Patel encouraged participants to consider a broader definition of difficult-to-treat disease, particularly for patients who may be unwilling or unable to undergo extensive surgical procedures.

One clinical scenario involved a patient with an infiltrative BCC of the medial canthus extending toward the nasal sidewall. Participants discussed the potential challenges of surgical reconstruction and whether systemic therapy could be considered before proceeding with an invasive intervention.

The case highlighted the importance of multidisciplinary collaboration and shared decision-making when evaluating tumors in anatomically sensitive locations.

Comparing Vismodegib and Sonidegib

A central focus of the roundtable was the distinction between vismodegib and sonidegib, 2 oral HHIs used in the treatment of advanced BCC.

Although both agents inhibit the hedgehog signaling pathway, participants discussed differences in their pharmacokinetic properties, dosing requirements, adverse-effect profiles, and monitoring considerations.

The conversation revealed that prescribing familiarity remains a significant factor in treatment selection. Several participants reported greater experience with vismodegib because of their training or previous clinical use, whereas others described limited experience prescribing either medication.

Insurance coverage, concomitant medications, institutional experience, and patient-specific considerations were also identified as factors influencing treatment selection.

Patel emphasized the importance of understanding differences between the 2 therapies rather than approaching them as interchangeable treatment options.

The discussion also explored how the medications' pharmacokinetic characteristics may influence the timing of adverse effects, treatment interruptions, and patient counseling.

Addressing Adverse Effects and Treatment Tolerability

Treatment tolerability emerged as a major concern, particularly regarding muscle spasms and the burden of ongoing monitoring.

One participant described a previous experience prescribing vismodegib in which severe muscle spasms and the demands of adverse-effect management contributed to reluctance to use HHIs again.

To examine these challenges, Patel presented a case involving a patient receiving vismodegib who developed grade 2 muscle spasms that interfered with daily activities. The patient's creatine kinase level was approximately twice the upper limit of normal, prompting discussion about treatment modification.

Participants considered the role of temporary treatment interruptions, supportive management, and laboratory monitoring in addressing treatment-related adverse effects.

The group also discussed whether differences in drug half-life could influence symptom resolution following discontinuation and how these considerations might affect therapeutic decisions.

Panelists emphasized that adverse-effect counseling should begin before treatment initiation, allowing patients to better understand potential symptoms and the importance of reporting changes during therapy.

When Patients Decline Surgery

Another case involved a 52-year-old man with an ulcerated, infiltrative BCC on the nasal tip, with concern for deep invasion and possible cartilage involvement.

The patient worked in custom cabinetry and was unwilling to undergo surgery or radiation therapy because of concerns about treatment-related disruption to his daily life.

The scenario prompted discussion about the role of systemic therapy in patients whose tumors may be technically resectable but who decline conventional local treatments.

Participants acknowledged that treatment decisions must account for more than tumor characteristics alone, including occupational responsibilities, cosmetic concerns, and patient preferences.

The panel considered how HHIs might be incorporated into treatment planning for appropriately selected patients, particularly when surgery could involve extensive reconstruction or compromise quality of life.

The discussion also addressed the potential role of tumor reduction before subsequent treatment, as well as the challenges of determining appropriate treatment duration.

Individualizing Treatment Goals

Throughout the roundtable, participants emphasized that treatment goals may differ substantially depending on patient age, overall health, life expectancy, and disease burden.

For younger patients, durable tumor clearance may remain the primary objective. However, for older individuals or those with significant comorbidities, symptom relief, preservation of function, and minimizing treatment burden may take greater priority.

Panelists discussed the importance of evaluating outcomes beyond tumor shrinkage, including duration of response, disease control, and treatment tolerability.

The discussion also highlighted the need to reassess therapeutic goals throughout treatment, particularly when adverse effects or changes in patient preferences affect the feasibility of continued therapy.

Expanding Confidence in Systemic Treatment

As the discussion concluded, several participants acknowledged that reviewing the differences between vismodegib and sonidegib had increased their confidence in discussing systemic treatment options with patients.

Some noted that HHIs were not routinely considered during their initial surgical consultations, whereas others expressed interest in becoming more familiar with treatment selection and adverse-effect management.

Patel emphasized that individualized treatment decisions should incorporate patient history, comorbidities, concomitant medications, and therapeutic goals.

The roundtable reinforced the importance of moving beyond a surgery-first framework for every patient with difficult-to-treat BCC. By understanding the clinical distinctions between available HHIs and incorporating patient preferences into treatment planning, dermatologists may be better equipped to identify appropriate nonsurgical strategies and optimize long-term disease management.

References

1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Basal Cell Skin Cancer. Version 1.2026. Accessed November 12, 2026. https://www.nccn.org/professionals/physician_gls/pdf/nmsc.pdf
2. Dummer R, Guminski A, Gutzmer R, et al. The 12-month analysis from the phase 2 BOLT trial: sonidegib in patients with advanced basal cell carcinoma. J Am Acad Dermatol. 2016;75(1):113-125.e5. doi:10.1016/j.jaad.2016.02.1226