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

Background Hedgehog inhibitors (HHIs) should be offered to patients with advanced basal cell carcinoma (BCC) as a first-line treatment. Two systemic HHIs are currently available: sonidegib and vismodegib.Objectives As there is no head-to-head trial of sonidegib vs. vismodegib and very few comparative studies have been published, we aimed to prospectively describe our long-term approach to managing advanced BCC based on our 10 years of experience with HHIs.Methods We undertook a prospective, monocentric and descriptive study in Florence, Italy. Patients who were treated with sonidegib and/or vismodegib for advanced BCC according to the European Association of Dermato-Oncology 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 a clinicopathologically confirmed diagnosis of advanced BCC. Of the 66 patients, 40 (61%) were treated with vismodegib, 19 (29%) received sonidegib and 7 (11%) were switched to sonidegib after vismodegib discontinuation. Among the 40 evaluable vismodegib-treated patients, the overall response rate (ORR) was 65%, with complete response (CR) in 28% of cases. The disease control rate was 85%. Among the 19 evaluable patients treated with sonidegib, the ORR and CR rates were 89% and 37%, respectively. Regarding patients who switched from vismodegib to sonidegib (mainly patients who had adverse events with vismodegib previously), the ORR was 71%, with CR in 43% of cases.Conclusions The efficacy demonstrated by sonidegib is greater than reported in the pivotal studies, with an ORR of 89% (vs. 60.6%), a CR rate of 37% (vs. 22.7%) and a PR rate of 53% (vs. 37.9%). Another element of innovation was the analysis of the subgroup of patients who switched from vismodegib to sonidegib, with an ORR of 71% (CR 43%, PR 29%). This, in relation to the possibility of developing resistance during therapy with HHIs, represents a promising result, suggesting a maintenance of effectiveness of the target therapy even in patients who are not naive to it.There are no head-to-head trials of sonidegib vs. vismodegib and very few comparative studies have been published. Therefore, we aimed to prospectively describe our long-term approach to managing advanced basal cell carcinoma (BCC) based on our 10 years of experience with hedgehog inhibitors (HHIs). In our study the efficacy demonstrated by sonidegib is greater than reported in the pivotal studies, with an overall response rate (ORR) of 89.5% (vs. 60.6%), a complete response (CR) rate of 36.8% (vs. 22.7%) and a partial response (PR) rate of 52.6% (vs. 37.9%). Another element of innovation was the analysis of the subgroup of patients who switched from vismodegib to sonidegib, with an ORR of 71.4% (CR 42.9%, PR 28.5%). Our study provides valuable data regarding the clinical management of difficult-to-treat BCC and confirms the safety and effectiveness of treatment with HHIs.