Intracranial regression of an advanced basal cell carcinoma using sonidegib and itraconazole after failure with vismodegib

BCC: basal cell carcinoma Hh: hedgehog HIV: human immunodeficiency virus SMO: smoothened protein INTRODUCTION Locally advanced or metastatic basal cell carcinoma (BCC) has traditionally been difficult to treat. Options for unresectable tumors have been limited to cisplatin-based chemotherapy or palliative radiation therapy. With the advent of molecularly targeted drugs to the hedgehog (Hh) pathway, another option is now available. In some cases, these new drugs have already provided patients with significant increases in overall survival rates. Vismodegib was the first drug within this group to be commercially available in January of 2012. It inhibits a transmembrane protein known as smoothened (SMO), which in turn down regulates the expression of Gli genes that are responsible for promoting tumorigenesis. Sonidegib, which targets the same SMO protein, was the second to be approved by the US Food and Drug Administration (FDA) for patients in 2015. In addition to these newly approved drugs, itraconazole, an older antifungal medication, has recently been identified as an inhibitor of the same pathway, albeit through a different mechanism, to reduce BCC tumor load in humans. Here we present a case of a patient with locally advanced BCC of the ethmoid sinus and brain who subsequently had resistance to vismodegib but then responded to a second round of combination treatment using sonidegib and itraconazole.