title: An Investigator-Initiated Open-Label Trial of Sonidegib in Advanced Basal Cell Carcinoma Patients Resistant to Vismodegib.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Stanford, California.
authors.forename: Christina
authors.initials: C
authors.lastname: Danial
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Stanford, California.
authors.forename: Kavita Y
authors.initials: KY
authors.lastname: Sarin
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Stanford, California.
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Oro
authors.affiliation: Department of Dermatology, Stanford University School of Medicine, Stanford, California. alschang@stanford.edu.
authors.forename: Anne Lynn S
authors.initials: AL
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation; D009367:Neoplasm Staging; D011487:Protein Conformation; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D019233:Retreatment; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D000072086:Smoothened Receptor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; C538724:HhAntag691; D011725:Pyridines; C491023:SMO protein, human; D000072086:Smoothened Receptor; C561435:sonidegib