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Vismodegib: A Review in Advanced Basal Cell Carcinoma

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Abstract

Vismodegib (Erivedge®) is the first-in-class, oral small molecule inhibitor of the Hedgehog (Hh) pathway, abnormal activation of which is associated with basal cell carcinoma (BCC). In the USA, vismodegib is indicated for the treatment of adults with metastatic BCC (mBCC) or with locally-advanced BCC (LaBCC) that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. Similarly, in the EU, vismodegib is indicated for the treatment of adult patients with symptomatic mBCC, or with laBCC inappropriate for surgery or radiotherapy. The full European approval of vismodegib was based on the results of two phase II, open-label, noncomparative, international trials (ERIVANCE BCC and STEVIE), both of which showed high rates of tumour control in the indicated patient populations, including individuals with or without Gorlin syndrome. These studies also showed that vismodegib has an acceptable and manageable tolerability profile characterized by a number of class-related treatment-emergent adverse events, including muscle spasms, taste disturbances, alopecia, weight loss and asthenia (fatigue). Primary and secondary resistance to vismodegib has been documented, albeit at a low rate compared with some other targeted therapies. Vismodegib is therefore an effective and generally well tolerated systemic therapy for patients with mBCC and laBCC that can no longer be suitably controlled with surgery and/or radiotherapy. Historically, it is the first member of a class of drugs (Hh pathway inhibitors) that are now considered to be first-line treatment options for such individuals.

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Acknowledgements

During the peer review process, the manufacturer of vismodegib was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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  1. Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand

    James E. Frampton

  2. Department of Dermatology, Hôpital Saint Louis, Université Paris 7, Paris, France

    Nicole Basset-Séguin

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Correspondence to James E. Frampton.

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The preparation of this review was not supported by any external funding.

Conflict of interest

James Frampton is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest. Nicole Basset-Séguin has received grants or has grants pending (Roche, Genentech); has received consulting fees or honoraria (Roche, Novartis, Pierre Fabre, Leo Pharmaceuticals, Galderma); and has received support for study-related travel, manuscript preparation or other purposes (Galderma, Roche, Leo Pharmaceuticals).

Additional information

The manuscript was reviewed by: C. Berking, Department of Dermatology and Allergy, University Hospital Munich (LMU), Munich, Germany; L. Dirix, Oncology Centre, GZA Hospitals St-Augustinus, Antwerp, Belgium; K. Fife, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge, UK; D. Ioannides, First Department of Dermatology-Venereology, Aristotle University Medical School, Thessaloniki, Greece.

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Frampton, J.E., Basset-Séguin, N. Vismodegib: A Review in Advanced Basal Cell Carcinoma. Drugs 78, 1145–1156 (2018). https://doi.org/10.1007/s40265-018-0948-9

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