Systemic Targeted Treatments for Basal Cell Carcinoma

Area of Science:

• Oncology
• Dermatology

Background:

• Sonic hedgehog (SHH) inhibitors, vismodegib and sonidegib, are approved first-line treatments for locally advanced basal cell carcinoma (BCC).
• Vismodegib is also approved for metastatic BCC, while cemiplimab is a second-line immune checkpoint inhibitor (ICI) option.
• SHH inhibitors show comparable efficacy but common adverse effects often necessitate treatment cessation.

Purpose of the Study:

• To review the current landscape of systemic therapies for locally advanced and metastatic basal cell carcinoma (BCC).
• To discuss the efficacy, safety, and management of adverse effects associated with SHH inhibitors.
• To explore future directions including alternative dosing, combination therapies, and neoadjuvant use of SHH inhibitors.

Main Methods:

• Review of current literature on SHH inhibitors and immune checkpoint inhibitors for basal cell carcinoma (BCC).
• Analysis of efficacy and adverse event profiles from clinical trials and real-world data.
• Discussion of emerging strategies for managing treatment-related toxicities and overcoming drug resistance.

Main Results:

• Vismodegib and sonidegib demonstrate significant efficacy in BCC but share similar adverse effect profiles.
• Adverse events are a major cause of treatment discontinuation, prompting investigation into dose modifications.
• Emerging concerns regarding drug resistance highlight the need for maintenance regimens and combination therapies.

Conclusions:

• SHH inhibitors are effective for BCC, but side effect management is crucial for treatment adherence.
• Further research into alternative dosing, combination strategies (e.g., with radiotherapy), and neoadjuvant use is warranted.
• Optimizing treatment strategies for BCC is essential to improve long-term outcomes and address recurrence and resistance.