LAUSR

Dear Editor Hedgehog inhibitors (HHIs) were recently introduced to the market for the treatment of locally advanced basal cell carcinoma (laBCC) and metastatic BCC demonstrating a high response rate in pivotal studies. Much experience has been achieved with the first in class agent vismodegib. Sonidegib, the latest introduced HHI to the market, has similar efficacy and tolerability profiles as reported in the registrative study. However, real-life data on its efficacy and safety profile are scarce. Here, we report our experience with sonidegib in the treatment of laBCC. Five patients with laBCC, of whom four were men, aged 75 to 86 years (mean age 79.6 years) were treated with sonidegib 200 mg/daily starting in December 2019 (Table S1). All laBCCs were located on the head/neck area, and two patients had also BCCs on the trunk. All patients had previously experienced surgical excision of their BCCs, and two patients had previously received both surgery and radiotherapy. Renal and hepatic function were tested before starting therapy and monthly during treatment. In one case, a complete response (CR, evaluated clinically) was achieved after 9 months of therapy, the patient then discontinued treatment and is currently under follow-up; three patients are currently under treatment with partial responses after 6 months and partial response was first achieved 1 month after starting treatment; and one patient is lost to follow-up. Adverse events (AEs) were experienced by all patients, including muscle spasm, fatigue and alopecia, all classified as mild (grade I or II). In one patient, a worsening of the hepatic function was documented 1 month after starting sonidegib, with increase in transaminase levels (3-fold higher than basal levels), and remission was seen 1 month after stopping the therapy. The patient was then lost to follow-up. The onset of alopecia, fatigue and muscle spasms was reported few months after treatment initiation (from 3 to 6 months later). The onset of side effects did not correlate with treatment response. Villani et al first reported one case of laBCC successfully treated with sonidegib, with CR (clinically evaluated) 3 months after starting treatment and with no side effects. In our experience, the complete clinical resolution was achieved in one case after 9 months of therapy. Overall, our experience is in line with previous data from the Bolt study (the pivotal study for sonidegib) that showed an overall response rate measured by response evaluation criteria in solid tumor