PURPOSE: To assess the tumor response to the smoothened (SMO) inhibitor, 
sonidegib (LDE225), in patients with an advanced basal cell carcinoma (BCC) 
resistant to treatment with vismodegib (GDC0449).
EXPERIMENTAL DESIGN: Nine patients with an advanced BCC that was previously 
resistant to treatment with vismodegib were given sonidegib in this 
investigational, open-label study. Tumor response was determined using the 
response evaluation criteria in solid tumors. SMO mutations were identified 
using biopsy samples from the target BCC location.
RESULTS: The median duration of treatment with sonidegib was 6 weeks (range, 
3-58 weeks). Five patients experienced progressive disease with sonidegib. Three 
patients experienced stable disease and discontinued sonidegib either due to 
adverse events (n = 1) or due to election for surgery (n = 2). The response of 
one patient was not evaluable. SMO mutations with in vitro data suggesting 
resistance to Hh pathway inhibition were identified in 5 patients, and none of 
these patients experienced responses while on sonidegib.
CONCLUSIONS: Patients with advanced BCCs that were previously resistant to 
treatment with vismodegib similarly demonstrated treatment resistance with 
sonidegib. Patients who have developed treatment resistance to an SMO inhibitor 
may continue to experience tumor progression in response to other SMO 
inhibitors.