Vismodegib for Advanced Basal Cell Carcinoma

Vismodegib is an oral drug that is designed to selectively inhibit abnormal signaling in the Hedgehog pathway, which is an underlying molecular driver of BCC. It binds to and inhibits Smoothened, a transmembrane protein involved in Hedgehog signal transduction.

Vismodegib was reviewed under the US Food and Drug Administration (FDA) priority review program offering an expedited 6-month review. It was approved for use in advanced basal cell carcinoma (BCC) ahead of the prescription user fee goal date, which was March 8, 2012.

 

Clinical Implications

• The FDA has approved vismodegib for treatment of BCC that has metastasized or relapsed after treatment with surgery, or for treatment of BCC in patients who are not candidates for surgery or radiation.

• The recommended dose of vismodegib is one 150-mg capsule orally once daily, with or without food. If a dose is missed, it should not be made up but should be resumed with the next scheduled dose.

• Vismodegib is pregnancy category D and can cause fetal harm. Men as well as women should be advised concerning pregnancy prevention and planning. Breast-feeding mothers should discontinue either vismodegib or breast-feeding, depending on how important the drug is to the mother. The safety and efficacy of vismodegib have not been established in pediatric patients or in patients with hepatic or renal impairment. 

The most common adverse reactions (incidence of 10% or more) were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias, vomiting, and ageusia.