Common forms of basal cell carcinoma of the skin: The first experience with sonidegib in the B-SURE observational study in Russia

Background. Locally advanced (laBCC) and metastatic basal cell carcinoma of the skin (mBCC) have a poor prognosis. Hedgehog (Hh) pathway inhibitors, such as vismodegib and sonidegib, are highly effective in treatment of advanced forms of BCC.

Aim. To evaluate the efficacy and safety of sonidegib in the investigator-initiated observational study B-SURE (Basal cell carcinoma – Sonidegib Use in Real-world Evidence) in patients with laBCC and mBCC in real-world clinical practice in the Russian Federation as first-line therapy (in patients with no history of treatment with Hh inhibitors), as well as in patients with a history of treatment with vismodegib (another Hh pathway inhibitor).

Materials and methods. The study included 10 patients, 9 with laBCC and 1 with mBCC. Patients visited clinical center in accordance with routine clinical practice and underwent standard procedures and examinations in accordance with clinical guidelines and the physician’s decision. Visit intervals were 3–4 months. Data on patients’ use of sonidegib was collected during visits to the clinical site, and the efficacy of sonidegib therapy was assessed according to RECIST 1.1 criteria. The patients also completed the EORTC QLQ-C30, version 3, and the EQ-5D-5L, version 1.2, before starting sonidegib therapy and every 3 months thereafter during routine visits to clinic.

Results. At the time of data analysis (September 2025), the efficacy of sonidegib therapy was evaluated in 9 patients, while tolerability and safety were evaluated in all 10 patients. Three patients had a history of vismodegib therapy, which was discontinued due to disease progression (n=1), intolerance (n=1), and intolerance with a complete clinical response (n=1). The median time from diagnosis to the development of laBCC and mBCC was 67.5 months. In patients with no prior vismodegib treatment, objective responses were observed in 4 of 7 patients (2 complete, 2 partial responses), yielding an objective response rate (ORR) of 57%. In patients with a history of vismodegib treatment, an objective response was reported in 1 of 3 (complete response in 1), yielding an ORR of 33.3%. The safety profile of sonidegib included adverse events (AEs) in 7 (70%) of 10 patients, mainly of Grade 1-2, which did not require a change in the dose regimen. Severe AEs (Grade 3-4) leading to discontinuation were reported in 1 patient (10%). It is noteworthy that in three patients with severe AEs during previous vismodegib therapy, sonidegib treatment was not associated with such complications, suggesting different safety profiles of these agents.

Conclusion. For the first time, the efficacy of sonidegib, with an ORR of 57%, was demonstrated in a Russian population of Hh inhibitor-naive patients with laBCC and mBCC. Sonidegib demonstrated an acceptable safety profile, with a low discontinuation rate (10%) due to AEs. Particular attention should be given to the favorable tolerability of sonidegib in patients with a history of severe toxicity during vismodegib therapy, which expands the therapeutic options in case of intolerance to another Hh-inhibitor.