Vismodegib for Locally Advanced Basal Cell Carcinoma: Descriptive Analysis of a Case Series and Comparison to the Literature

September 2015 | Volume 14 | Issue 9 | Original Article | 956 | Copyright © September 2015


Kathleen Sikora Viscusi MD and C. William Hanke MD MPH

Laser and Skin Surgery Center of Indiana, Carmel, IN

Abstract
OBJECTIVE: This case series explores the use of vismodegib to treat locally advanced basal cell carcinoma (laBCC), with a focus on tolerability, efficacy, and outcomes after treatment cessation.
METHODS: Data from patients who underwent vismodegib treatment for laBCC at a single institution from 3/6/2012 through 3/15/2015 was utilized in this study. For all included cases, treatment responses as recorded at the first follow-up after treatment cessation were assessed and are reported as complete clinical response (CCR), partial clinical response (PCR), stable disease, or progressive disease. In cases of CCR, clinical disease free survival (DFS) was calculated as the time from cessation of vismodegib until last available follow-up, death, or recurrence. Data pertaining to side effects and adverse events was also recorded, and results are presented using descriptive statistics.
RESULTS: A total of 24 patients and 31 tumors met inclusion criteria. CCR was observed in 17 of 31 tumors (55%), and 13 of 31 tumors (42%) demonstrated PCR. Stable disease was seen in one patient (one tumor) (3%). No cases demonstrated clinical tumor progression during treatment. The mean clinical DFS at time of data cut off for all cases of CCR was 9.3 months (range 2-21 months). In cases of PCR, the mean reduction in tumor size was 52% (range, 11%-80%). Only two patients (8%) discontinued treatment secondary to side effects.
CONCLUSION: Each patient and each tumor responds uniquely to vismodegib treatment, including variable tumor responses and a wide range of side effects and tolerability. This study highlights important unique observations, and our data as a whole adds to previously published studies, leading to thought provoking questions. Overall, the FDA approval of vismodegib for advanced basal cell carcinoma has markedly improved the prognosis and care of affected patients.

J Drugs Dermatol. 2015;14(9):956-962.

INTRODUCTION

Basal cell carcinoma (BCC) is the most common human malignancy and accounts for ~80% of all nonmelanoma skin cancers (NMSC).1 Although rarely fatal, left untreated, BCCs continue to grow, often invading and destroying local tissue. In locally advanced basal cell carcinoma, surgery and radiation may lead to significant loss of vital function and intolerable morbidity, presenting a therapeutic challenge. Molecular and genetic studies have shown that alteration of the Hedgehog (Hh) signaling pathway is the key driver in the pathogenesis of BCC.2 After a single phase-2 clinical trial (ERIVANCE), vismodegib (Erivedge TM, GDS-0449, Genentech), an oral small-molecule inhibitor of the Hh pathway, was approved by the Food and Drug Administration (FDA) in 2012 for the treatment of advanced BCC (aBCC), including locally advanced BCC (laBCC) and metastatic BCC (mBCC).3 Despite FDA approval, the efficacy and safety of vismodegib is still being extensively explored.4 In particular, concern has been expressed regarding tumor recurrences and long term outcomes, and more data is needed to identify the ideal duration of treatment and the incidence of recurrence on and off medication.4,5,6 This case series explores the use of vismodegib to treat laBCC, with a focus on tolerability, efficacy, and outcomes after treatment cessation.

METHODS

This study was approved by the institutional review board and performed in accordance with the Declaration of Helsinki. Data from patients who underwent vismodegib treatment for laBCC at a single institution from 3/6/2012 through 3/15/2015 was utilized in this study. Prior to vismodegib treatment, informed consent was obtained from all patients and if applicable, their power of attorney. Each patient had clinically and histologically confirmed laBCC. Vismodegib treatment was considered in cases for which curative resection was deemed unlikely and/or when significant morbidity and/or deformity were anticipated with surgery. Curative resection was considered unlikely based on history of recurrence combined with clinical exam findings and/or histologic findings during initial stages of Mohs micrographic surgery (MMS). All cases were previously treated with radiation or not amenable to radiation therapy due to patient preference (including social and
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