Sonidegib for the treatment of advanced basal cell carcinoma

Area of Science:

• Dermato-oncology
• Molecular biology
• Pharmacology

Background:

• Advanced and metastatic basal cell carcinomas (BCCs) pose significant medical challenges, often causing disfigurement and impacting quality of life.
• The hedgehog (Hh) signaling pathway is crucial in BCC pathogenesis, leading to the development of smoothened (SMO) inhibitors.
• Sonidegib is a second-generation SMO inhibitor investigated in a randomized trial with stringent disease assessment criteria.

Purpose of the Study:

• To evaluate Sonidegib as a treatment for advanced basal cell carcinoma (BCC).
• To assess the efficacy and safety of Sonidegib, a hedgehog (Hh) pathway inhibitor.
• To explore the pharmacodynamic effects and disease assessment of Sonidegib in a randomized trial.

Main Methods:

• A comprehensive literature search of Medline and key dermato-oncology meeting abstracts was conducted.
• Inclusion of all available papers and abstracts relevant to Sonidegib and advanced BCC.
• Utilized stringent disease assessment criteria including annotated photographs, MRI, and multiple biopsies.

Main Results:

• Sonidegib demonstrates promise as a treatment for advanced BCC and other Hh-driven malignancies.
• The drug exhibits favorable pharmacokinetic properties.
• Class-specific toxicities were observed, including dose-dependent adverse events affecting muscular and taste bud homeostasis, gastrointestinal symptoms, and hair growth.

Conclusions:

• Sonidegib is a promising agent for advanced BCC and other Hh signaling-driven cancers.
• It possesses favorable pharmacokinetics and a distinct toxicity profile.
• Sonidegib warrants further investigation in combination therapies, with other antibodies, or alternative dosing schedules.