Multicenter Retrospective Case Series on the Real‐World Experience With Sonidegib for the Management of Gorlin Syndrome

ABSTRACT Background Gorlin syndrome (GS) is a hereditary genodermatosis characterised by the development of multiple basal cell carcinomas (BCC). The hedgehog pathway inhibitors (HPI) like sonidegib have been shown to be effective, but the frequency of adverse events (AE) limits their long‐term use. Dose modifications and off‐therapy periods are frequently necessary to improve tolerability. Objectives To describe the dosing regimens employed during treatment with sonidegib for GS in clinical practice and evaluate the efficacy and tolerability of its long‐term use. Methods Multicenter retrospective study involving 10 referral centres in Spain including patients with GS who received treatment with sonidegib for at least 12 weeks. Results Twenty‐four patients were included: 11 (45.8%) women and 13 (54.2%) men, with a mean age of 50.7 ± 12.1 years. The mean duration of treatment with sonidegib was 10.4 ± 5.1 months. Sonidegib was started at 200 mg daily in 22 (91.7%) patients. Thirteen (59.1%) of them switched to alternate‐day dosing motivated most frequently by the development of AEs (76.9%), and less frequently by dosing convenience (23.1%). Two patients followed on–off regimens. Four patients received an off‐label regimen of 2–3 tablets per week. Nine (37.5%) of the 24 patients achieved a complete response, 13 (54.2%) a partial response and 2 (8.3%) presented stable disease. Twenty (83.3%) patients presented at least one AE, the most frequent being alopecia (45.8%), followed by muscle cramps (37.5%), dysgeusia (29.2%), asthenia (29.2%), weight‐loss (20.8%), diarrhoea (12.5%) and nausea (8.3%). Conclusions Our data on the use of sonidegib for GS in clinical practice show similar response rates to those reported in previous studies and improved tolerability compared to pivotal studies. Regimen modifications are frequently used in clinical practice to improve AEs. Although the alternate‐day dose is the most common modification, dermatologists also resort to off‐label regimens for this purpose.