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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- Wolter M, Reifenberger J, Sommer C, Ruzicka T, Reifenberger G. Mutations in the human homologue of the Drosophila segment polarity gene patched (PTCH) in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res. 1997;57(13):2581-2585.
- Xie J, Murone M, Luoh SM, et al. Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature. 1998;391(6662):90-92.
- Hahn H, Wicking C, Zaphiropoulous PG, et al. Mutations of the human homolog of Drosophila patched in the nevoid basal cell carcinoma syndrome. Cell. 1996;85(6):841-851.
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- Tang JY, Mackay-Wiggan JM, Aszterbaum M, et al. Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N Engl J Med. 2012;366(23):2180-2188.
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- Narayanan K, Hadid OH, Barnes EA. Mohs micrographic surgery versus surgical excision for periocular basal cell carcinoma. Cochrane Database Syst Rev. 2012;2:CD007041.
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- Chang AL, Atwood SX, Tartar DM, Oro AE. Surgical excision after neoadjuvant therapy with vismodegib for a locally advanced basal cell carcinoma and resistant basal carcinomas in Gorlin syndrome. JAMA Dermatol. 2013;149(5):639-641.
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