Efficacy of Vismodegib for the Treatment of Orbital and Advanced Periocular Basal Cell Carcinoma

Abstract

To evaluate the effectiveness of vismodegib, a Hedgehog pathway inhibitor, in treating orbital and advanced periocular basal cell carcinoma (BCC) in Israeli multidisciplinary medical centers. Retrospective case series. Background, treatment, and outcome data were retrospectively collected from the medical records of all patients with locally advanced and metastatic orbitalor periocular BCC treated with vismodegib in 2012-2017 at 2 tertiary medical centers. The cohort included 21 patients (16 male) of median age 76 years with periocular (n=6) or orbital (n=15) BCC. Median duration of treatment was 9months, with follow-up of 26months (range 9-60months) overall and 17months after treatment cessation. Clinical response was complete in 10 patients, partial in 10 patients, and stable in 1 patient. Among the complete responders, 5 maintained a complete response at 16months, and 3 who stopped treatment had a recurrence 8months later. Almost all treatment-related adverse reactions were graded 1 or 2 (low-grade). The most common grade 1 or 2 complications were muscle spasm (76%), followed by dysgeusia (57%), alopecia (47%), weight loss (47%) and decreased appetite (19%). The only grade 3 or 4 adverse event was hepatotoxicity (10%). Eight patients discontinued treatment because of side effects. Five patients died, most from reasons unrelated to vismodegib therapy, except for 1 patient who died from possibly treatment-related sepsis (grade 5 adverse event). To our knowledge, this is the only study generated outside the United States and Europe, and it represents the largest study to date on vismodegib therapy for locally advanced periocular BCC. Treatment according to an individualized maximally tolerated dose may achieve a comparable response to the ERIVANCE protocol. Longer-term studies are needed to assess prognosis.