Vismodegib for Preservation of Visual Function in Patients with Advanced Periocular Basal Cell Carcinoma: The VISORB Trial.

Background Basal cell carcinoma (BCC) is a common skin cancer often curable by excision; however, for patients with BCC around the eye, excision places visual organs and function at risk. Here we test the hypothesis that use of the hedgehog inhibitor vismodegib will improve vision-related outcomes in patients with orbital and extensive periocular BCC (opBCC). Methods In this open label, non-randomized phase 4 trial, we enrolled patients with globe- and lacrimal drainage system-threatening opBCC. To assess visual function in the context of invasive periorbital and lacrimal disease, we utilized a novel Visual Assessment Weighted Score (VAWS) in addition to standard ophthalmic exams. Primary endpoint was VAWS, with a score of 21/50 (or greater) considered successful, signifying globe preservation. Tumor response was evaluated using RECIST v1.1. Surgical specimens were examined histologically by dermatopathologists. Results In 34 patients with opBCC, mean VAWS was 44/50 at baseline, 46/50 at 3 months, and 47/50 at 12 months or post-surgery. 100% of patients maintained successful VAWS outcome at study endpoint. Compared to baseline, 3% (95% confidence interval [CI], 0.1 to 15.3) experienced major score decline (5+ points), 14.7% (95% CI, 5 to 31.1) a minor decline (2-4 points), and 79.4% a stable or improved score (95% CI, 62.1 to 91.3). 56% (19) of patients demonstrated complete tumor regression by physical examination, and 47% (16) had complete regression by MRI/CT. 79.4% (27) of patients underwent surgery of which 67% (18) had no histologic evidence of disease, 22% (6) had residual disease with clear margins, and 11% (3) had residual disease extending to margins. Conclusions Vismodegib treatment, primary or neoadjuvant, preserves globe and visual function in patients with opBCC. Visorb VISmodegib for ORbital and periocular Basal cell carcinoma, ClinicalTrials.gov Identifier: NCT02436408 (https://clinicaltrials.gov/ct2/show/NCT02436408) IMPLICATIONS FOR PRACTICE: Use of the anti-hedgehog inhibitor vismodegib resulted in preservation of end-organ function, specifically with regard to preservation of the eye and lacrimal apparatus when treating extensive periocular basal cell carcinoma..Vismodegib as a neoadjuvant also maximized clinical benefit while minimizing toxic side effects. This is the first prospective clinical trial to demonstrate efficacy of neoadjuvant anti-hedgehog therapy for locally advanced periocular basal cell carcinoma, and the first such trial to demonstrate end-organ preservation.