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Introduction: Basal cell carcinoma (BCC) is the most common skin malignancy in Caucasians. Globally, about 20% of BCCs involve the periocular region. The treatment of periocular BCC may be very challenging because of its proximity to the intracranial structures. Thus, early diagnosis and early treatment is mandatory. Recently, the introduction of Hedgehog pathway inhibitor therapy revolutionized the management of unresectable BCCs. The aim of our study was to evaluate the outcome of sonidegib treatment in patients affected by periocular locally advanced (la) BCC at our skin cancer center. Methods: A 3-year retrospective study was carried out enrolling patients with periocular laBCC treated with sonidegib. Therapeutic response was defined as complete remission (CR) in case of complete regression of the tumor, partial remission (PR) in case of tumor regression not achieving complete remission, and stable disease (SD). Results: A total 16 patients (11 men and 5 women; medium age 71.6 ± 11.5 years) with periocular laBCCs undergoing treatment with 200 mg/day of sonidegib were included in our study. Patients included in the study were treated for at least 6 months for a median duration of 9 months. Overall, CR was reported in 9/16 (56.2%) patients, PR was reported in 4/16 patients (25%), and tumor remained stable in 3 patients (18.8%). No cases of disease progression were collected. Fourteen out of 16 patients experienced multiple adverse events (AEs): dysgeusia was reported in 12 (75%) patients, muscle spasms in 13 (81%) patients, and 7 (43.7%) patients presented with alopecia. However, all of the AEs were mild and none required treatment discontinuation. Conclusion: To the best of our knowledge, this is the first study investigating the effectiveness and safety of sonidegib in the management of BCC localized at the periocular region. Even if limited, our study suggests this drug as a valuable and safe option in periocular BCC management. [ABSTRACT FROM AUTHOR]