Vismodegib: A Hedgehog Pathway Inhibitor for Locally Advanced and Metastatic Basal Cell Carcinomas

October 2013 | Volume 12 | Issue 10 | Supplement Individual Articles | 154 | Copyright © October 2013

Joesph F. Sobanko MD,a Jonathan Okman BA MBA,b and Christopher Miller MDa

aDivision of Dermatologic Surgery and Cutaneous Oncology, University of Pennsylvania, Philadelphia, PA
bPerelman School of Medicine, University of Pennsylvania, Philadelphia, PA

BCC in a biopsy specimen), while 47% and 22% experienced a partial response with vismodegib.15,16

Questions That Still Remain

While early data appear promising, there is still much to be determined regarding vismodegib’s role in BCC treatment. First, the category of “inoperable” BCC is rather subjective and must be better developed. Many recurrent BCCs that are considered inoperable by one surgeon may be deemed surgically appropriate by another surgeon. This decision has significant financial implications too, because the cost of 10 months of vismodegib is $75,000 compared with less than $2,000 for the surgical treatment of most BCCs.18,19
Second, vismodegib may not offer better results than chemotherapeutic agents currently used for metastatic BCCs. Cisplatin-containing regimens have been associated with overall response rates of up to 77%, including complete response rates of up to 45%.20-23 Neutropenia and renal toxicity are feared adverse events (AEs) of cytotoxic cisplatin-based regimens; however, the side effects from vismodegib frequently result in medication termination.24 Twenty-seven percent of NBCCS patients at 8 months and 54% of patients at 18 months discontinued their medication because of side-effect intolerability.17 The most frequently reported AEs are muscle spasms, dysgeusia, weight loss, fatigue, nausea, diarrhea, and alopecia.15,16,24
Finally, the proper duration of vismodegib therapy must be determined. It appears that BCCs and other tumors that involve the Hh pathway develop resistance to vismodegib with subsequent disease progression.25,26,27 This may be the result of a missense mutation in the SMO receptor that decreases vismodegib’s affinity for the receptor. Additionally, the rebound of BCCs after vismodegib cessation have been reported in one patient.28 Future avenues of research that warrant further investigation include the use of vismodegib as a neoadjuvant medication prior to surgical resection.29 Other medications such as such as itraconazole and arsenic trioxide may also offer promising results for vismodegib-resistant BCCs that acquire SMO mutations.30


The authors have no relevant conflicts of interest to disclose.


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Joesph F. Sobanko