Neoadjuvant Vismodegib and Mohs Micrographic Surgery for Locally Advanced Periocular Basal Cell Carcinoma

Abstract

Introduction: Vismodegib has shown a significant response rate in locally advanced periocular basal cell carcinoma. Long-term monotherapy is very difficult to accomplish due to primary or secondary resistance and side effects that limit the length of treatment. The use of Vismodegib as neoadjuvant followed by Mohs micrographic surgery is an option. Purpose: To report the use of neoadjuvant Vismodegib as an option for operable locally advanced basal cell carcinoma followed by Mohs surgery. Patients and Methods: The authors treated 8 locally advanced periocular basal cell carcinomas. Mean age was 76, and 6 of 8 were women. Mean size was 18 mm (12–30). Three were recurrent after surgery. Maximal clinical response was obtained at 4.8 months. Patients were operated at the mean time of 7.3 months. Results: Seven patients (87.5%) had a complete response and 1 (12.5%) progressed. Mohs micrographic surgery allowed to confirm a complete histologic response in 5 of 6 (83.3%) cases, and 1 patient refused surgery. All 7 patients are disease free after a mean follow-up of 12.4 months. All patients experienced adverse events. The most common included dysgeusia (100%) and muscle spasms (100%). Weight loss was present in 75% of the patients with a mean loss of 12.6 pounds and hair loss was seen in 50%. Only 1 (12.5%) patient withdraw from treatment because of intolerable muscle spasms. Conclusions: The authors believe there is a clear role for Vismodegib as neoadjuvant in locally advanced periocular basal cell carcinoma, even in operable cases. Specific indications beyond those already approved should be further discussed. Prospective studies to assess the combination of neoadjuvant Vismodegib followed by Mohs micrographic surgery in locally advanced periocular basal cell carcinoma with long-term follow-up are needed.

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

“…The pivotal study, a prospective nonrandomized clinical trial, revealed a 43% response rate among patients with locally advanced BCC and 30% response rate among patients with metastatic BCC, with a median duration of response of 7.6 months [ 8 ]. Prospective trials have assessed vismodegib as a neoadjuvant in a variety of body locations [ 17 , 18 , 19 ], and several case studies have highlighted the efficacy of vismodegib for preserving vision in patients with orbital BCC [ 20 , 21 , 22 , 23 , 24 , 25 ]. More recently, post hoc prospective analysis of the multisite multicountry Safety Events in Vismodegib study data showed either complete or partial response to vismodegib in 67% of patients [ 25 ].…”

Combination treatment of bilateral periocular sebaceous carcinomas with microsatellite instability with neoadjuvant pembrolizumab and Mohs surgery

“…Neoadjuvant therapy in Mohs surgery of eyelid tumours is a relatively new approach with the majority of reports considering the use of vismodegib for extensive periocular basal cell carcinoma 10 . Our case presents the first published report where neoadjuvant pembrolizumab was used to significantly reduce the tumour size, making the surgical defect significantly smaller than it would have occurred with initial untreated lesion.…”

Systemic Targeted Treatments for Basal Cell Carcinoma

“…Several small retrospective studies and case reports have documented successful treatment of both operable and inoperable periocular laBCC, with preservation of the eye in all patients. [59][60][61] An open-label trial of 15 patients with advanced BCC who received neoadjuvant vismodegib for 3 to 6 months prior to surgical excision reported a mean reduction of 35% in the final surgical defect size, with no recurrence at 22 months. 62,63 The latest and largest study performed was a phase 2 open-label trial known as VISMONEO, where 44 of 55 laBCC patients (80%) receiving neoadjuvant vismodegib for a mean duration of 6 months (range, 4-10 months) achieved the primary end point of tumor surgical downstaging.…”