Efficacy, safety, and comparison of sonic hedgehog inhibitors in basal cell carcinomas: A systematic review and meta-analysis

Background: Sonic hedgehog inhibitors (SHHis) provide an additional treatment option for basal cell carcinomas (BCCs), especially for metastatic or locally advanced BCC. However, studies have been heterogeneous and lacked direct comparisons between molecules. Objective: To determine the efficacy and safety of the class of molecules SHHi for treating BCC and to compare them individually. Methods: We performed a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-compliant systematic review of studies followed by a meta-analysis. Results: Eighteen articles were included in our meta-analysis; 16 articles were combined for efficacy and 16 for safety. In locally advanced BCC, overall response rates (ORRs) were similar for vismodegib and sonidegib (69% vs 57%, respectively) but not complete response rates (31% vs 3%, respectively). In metastatic disease, the ORR of vismodegib was 2.7-fold higher than the ORR of sonidegib (39% vs 15%, respectively). For side effects affecting a majority of patients, prevalences for muscle spasms (67.1%), dysgeusia (54.1%), and alopecia (57.7%) were in similar proportions for sonidegib and vismodegib. Patients receiving sonidegib experienced more upper gastrointestinal distress than patients receiving vismodegib. Conclusion: SHHis induce a partial response to locally advanced BCC disease. Side effects are common, similar across molecules, associated with high discontinuation rates, and warrant discussion beforehand.