Management of advanced basal cell carcinoma with hedgehog inhibitors: a real-world prospective comparative study

Background: Hedgehog Pathway Inhibitors (HHIs) should be offered to patients with advanced BCC as a first line treatment. Two systemic HHIs are currently available: sonidegib and vismodegib. Objective: Since there is no head-to-head trial of sonidegib versus vismodegib and very few comparative studies have been published, we aimed at prospectively describing our long-term approach to manage advanced BCC based on our 10 years' experience with HHIs. Methods: We undertook a prospective, monocentric and descriptive study in Florence, Italy. Patients that were treated with Sonidegib and/or Vismodegib for advanced BCC according to EADO staging system were included from January 2013 to December 2023. Epidemiological, efficacy and safety data were collected. Results: The study population consisted of 66 patients with clinic-pathological confirmed diagnosis of advanced BCC. Of the 66 patients, 40(60.6%) were treated with vismodegib, 19(28.8%) with sonidegib, and 7(10.6%) were switched to sonidegib after vismodegib discontinuation. Among the 40 evaluable vismodegib-treated patients, the ORR was 65%, with CR in 27.5% of cases. DCR was 85%. Among the 19 evaluable patients treated with sonidegib, ORR and CR were 89.5% and 36.8%, respectively. Regarding patients switched from vismodegib to sonidegib (mainly patients who had AEs with vismodegib previously), the ORR was 71.4% with CR in 42.9% of cases. Conclusions: The efficacy demonstrated by Sonidegib is greater than reported in the pivotal studies with an ORR rate of 89.5%(vs 60.6%), a CR rate of 36.8%(vs 22.7%) and PR of 52.6%(vs. 37.9%). Another element of innovation was the analysis of the subgroup of patients switched from Vismodegib to Sonidegib with an ORR of 71.4% (CR 42.9%, PR 28.5%). This, in relation to the possibility of developing resistance during therapy with HHI represents a promising result, suggesting a maintenance of effectiveness of the target therapy even in patients who are not naïve to it.