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.