Vismodegib for Locally Advanced Periocular and Orbital Basal Cell Carcinoma: A Review of 15 Consecutive Cases

Abstract

Basal cell carcinoma (BCC) is the most common periocular skin cancer and can lead to significant morbidity. We assess the effectiveness of vismodegib, a first-in-class Hedgehog signaling pathway inhibitor, in the management of periocular and orbital BCCs based on clinical response, tolerability, and orbital content preservation. All patients with periocular or orbital BCCs who met criteria for vismodegib treatment were recruited prospectively between May 2012 and 2014 from 2 hospitals. Patients received oral vismodegib (150 mg daily) until disease progression, unacceptable toxicity, or withdrawal. All patients were followed up monthly. Patient demographics, tumor size, treatment duration including dosing regimen, adverse events, response rate, duration of response, progression-free survival, and disease-free survival were analyzed. All 15 patients had biopsy-proven BCCs with no metastatic disease at presentation. The mean age was 74 years and 10 patients (67%) had orbital involvement. The mean lesion longest dimension was 51 mm and 7 cases (47%) represented recurrence following previous surgery and/or radiotherapy. The mean treatment duration was 13 months and mean follow-up duration 36 months. Ten patients (67%) had a complete response, 3 (20%) had a partial response, and 2 had progressive disease following an initial partial response (13%). The partial response of 55% in 1 patient allowed subsequent surgical resection with clear margins. Vismodegib is effective for treating periocular and orbital BCCs with orbital salvage of patients who otherwise would have required exenteration. There is a neoadjuvant role for vismodegib but further studies are required.

Fig. 1.

BCC shrinkage in 15 patients treated with vismodegib. A partial response of 55% in 1 case allowed subsequent surgical clearance (*). Two patients had disease progression following a partial response of 90% (**) and 36% (***). They both underwent subsequent orbital exenteration and remain disease free at 2 years postoperative follow-up. There was 1 case of recurrence that required orbital exenteration (****) following a complete response of 21 months. The patient died 7 months later.

Fig. 2.

BCC of right forehead and upper eyelid with orbital invasion (case 1). Pre-vismodegib (A) and 4 months since treatment initiation (B). C, One year later.