Dose-Modulated Sonidegib Therapy for Periocular Basal Cell Carcinoma

This monocentric, open-label, real-world study investigated the clinical efficacy and tolerability of Sonidegib, a selective Hedgehog pathway inhibitor, in the treatment of locally advanced periocular basal cell carcinoma (laBCC). The study specifically focused on patients for whom standard surgical or radiotherapy options were contraindicated due to the risk of vision loss, functional impairment, or unacceptable cosmetic outcomes. A total of 12 adult patients with histologically confirmed periocular laBCC were enrolled at the Oculoplasty Unit of the University of Naples Federico II. Inclusion criteria targeted individuals with tumors in functionally or aesthetically sensitive locations-such as the eyelid margins, medial/lateral canthi, or deep orbital tissues-where conventional excision would require extensive, disfiguring surgery. All patients received oral Sonidegib 200 mg daily as first-line systemic therapy. A dose-modulation strategy was implemented in response to adverse effects or individual tolerance, allowing temporary drug interruption or reduced-frequency administration. This personalized therapeutic approach aimed to preserve treatment adherence and quality of life while maintaining tumor control. Patients were monitored through multidisciplinary follow-up visits at regular intervals, including dermatologic evaluation, photographic tumor documentation, and ophthalmologic assessments such as best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, and fundus examination. Tumor response was assessed using clinical measurements and standardized criteria adapted for periocular anatomy. The primary endpoint was the proportion of patients achieving disease control (complete response, partial response, or stable disease) without requiring exenteration or vision-threatening surgery. Secondary endpoints included time to response, duration of therapy, adverse event frequency and severity (graded per CTCAE), patient-reported functional and cosmetic outcomes, and post-treatment recurrence rates. This study offers preliminary real-world evidence that Sonidegib, when administered with a flexible dosing strategy, can achieve significant therapeutic responses while minimizing toxicity in patients with complex periocular laBCC. The results support its role as an eye-sparing, function-preserving alternative to surgery in selected cases.