Sonidegib for the treatment of advanced basal cell carcinoma

ABSTRACT

Introduction: Advanced and metastatic basal cell carcinomas (BCCs) are rare but still present a severe medical problem. These tumors are often disfiguring and impact the quality of life by pain or bleeding. Based on discovery of the hedgehog (Hh) signaling pathway and its role in the pathogenesis of BCCs, smoothened (SMO) inhibitors have been developed with Sonidegib being the 2nd in class. It is the only Hh pathway inhibitor investigated in a randomized trial accompanied by pharmacodynamic investigations. Also, the disease assessment criteria applied were more stringent than those used in trials of 1st developed SMO inhibitor – vismodegib, and required annotated photographs, MRI as well as multiple biopsies in case of regression.

Areas covered: All available papers from Medline and the abstracts of the most important dermato-oncology meetings were included.

Expert opinion: Sonidegib is a promising medication for advanced BCC and other malignancies, driven by Hh signaling. It presents favorable pharmacokinetic properties and causes class specific toxicity with dose dependent adverse events in muscular and taste bud homeostasis, gastrointestinal symptoms and hair growth. Early after treatment initiation, it impacts the immunesusceptibility of the tumor lesions. Sonidegib deserves further development in combination with other drugs or antibodies, or alternative dosing schedules.

KEYWORDS:

• Basal cell carcinoma
• Hh inhibitor
• SMO inhibitor
• sonidegib

Declaration of interest

R Dummer has received research funding from Novartis, Roche, and has been a consultant or had an advisory board relationship with Novartis, Roche, Ascend Pharma and Spirig. VC Amann has received honoraria from Merck Sharp & Dohme (MSD), and funding from Euronco Foundation and the Louis Widmer AG. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded.