Vismodegib ( Erivedge ), the first Food and Drug Administration ( FDA )-approved Hedgehog ( Hh ) signaling pathway inhibitor, in the treatment of advanced basal cell carcinoma ( BCC ).
Activation of the Hedgehog signaling pathway is well documented in basal cell carcinoma. Vismodegib is a small-molecule inhibitor of Hh signaling that acts by antagonizing the protein Smoothened ( SMO ), thereby preventing downstream transcriptional activation of genes involved in cell proliferation and survival.
Vismodegib was approved by the FDA in January 2012 for the treatment of recurrent, locally advanced basal cell carcinoma, or metastatic basal cell carcinoma for which surgery or radiation cannot be utilized.
A pivotal phase 2 trial evaluating 104 patients demonstrated that treatment with Vismodegib, 150 mg orally once daily, resulted in a 30% and 43% objective response rate in patients with metastatic basal cell carcinoma and locally advanced basal cell carcinoma, respectively.
The most common adverse effects from Vismodegib were mild to moderate and included muscle spasms, dysgeusia, decreased weight, fatigue, alopecia, and diarrhea.
However, clinical studies noted a high incidence of discontinuation of therapy by patients for reasons other than disease progression.
In conclusion, the approval of Vismodegib represents the only targeted, prospectively studied treatment option for patients with advanced basal cell carcinoma.
Further research assessing the utility of Vismodegib in the treatment of other malignancies and the development of resistance patterns will more clearly define the role of Hedgehog inhibition in the broader scheme of oncological disorders. ( Xagena )
Proctor AE et al, Ann Pharmacother 2014; 48: 99-106