Efficacy, Safety, and Comparison of Sonic Hedgehog Inhibitors in Basal Cell Carcinomas: A Systematic Review and Meta-Analysis

Publication date: Available online 10 July 2018

Source: Journal of the American Academy of Dermatology

Author(s): Pingxing Xie, Philippe Lefrançois

Abstract

Background

Sonic Hedgehog Inhibitors (SHHi) provide an additional treatment option for basal cell carcinomas (BCC), especially for metastatic or locally advanced BCC. However, studies have been heterogeneous and lacking direct comparisons between molecules.

Objective

To determine the efficacy and safety of SHHi, as a class of molecules, for treating BCC, and to compare them individually.

Methods

We performed a PRISMA-compliant systematic review of studies followed by a meta-analysis.

Results

Eighteen articles were included in our meta-analysis; sixteen articles were combined for efficacy and sixteen for safety. In locally advanced BCC, Overall Response Rates (ORR) were similar for vismodegib and sonidegib (69% vs. 57%), but not Complete Response Rates (31% vs. 3%). In metastatic disease, the ORR of vismodegib was 2.7-fold higher than the ORR of sonidegib (39% vs. 15%). For side effects affecting a majority of patients, combined prevalences were 67.1%, 54.1% and 57.7% for muscle spasms, dysgeusia, and alopecia, respectively, in similar proportions for sonidegib and vismodegib. Patients receiving sonidegib experienced more upper GI distress than patients receiving vismodegib.

Conclusions

SHHi as a class lead to partial responses for locally advanced BCC disease. Side effects are similar across molecules, common, associated with high discontinuation rates, and warrant discussion beforehand.