title: Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor, vismodegib.
abstract: BACKGROUND
  Vismodegib, a first-in-class Hedgehog pathway inhibitor, was US Food and Drug Administration (FDA) approved for advanced basal cell carcinomas (BCCs) based on a single, nonrandomized, phase-II trial. Consequently, additional clinical data are critical to confirm the efficacy and safety of vismodegib.
  
  
  OBJECTIVE
  We sought to assess efficacy and safety of vismodegib, while providing early drug access to patients with advanced BCC and limited treatment options.
  
  
  METHODS
  This was an open-label, multicenter study in patients with advanced BCC inappropriate for radiotherapy or surgery. Patients received 150 mg vismodegib daily until disease progression or intolerable toxicity. Tumor response was assessed via Response Evaluation Criteria in Solid Tumors version 1.0.
  
  
  RESULTS
  A total of 119 patients with advanced BCC took vismodegib for a median of 5.5 months. Objective responses occurred in 46.4% of locally advanced BCC and 30.8% of patients with metastatic BCC. Response was negatively associated with prior systemic therapy in patients with locally advanced BCC (P = .002). Mean follow-up for safety was 6.5 months, with muscle spasms (70.6%), dysgeusia (70.6%), alopecia (58.0%), and diarrhea (25.2%) as the most common adverse events.
  
  
  CONCLUSIONS
  Abbreviated follow-up time because of study termination upon FDA approval was a limitation.
  
  
  CONCLUSIONS
  This study provides important clinical data supporting the efficacy and safety of vismodegib. Larger studies are underway to assess predictors of response and long-term outcomes.
authors.affiliation: Stanford University School of Medicine, Stanford, California. Electronic address: alschang@stanford.edu.
authors.forename: Anne Lynn S
authors.initials: AL
authors.lastname: Chang
authors.affiliation: Ameriderm Research, Ormond Beach, Florida; Sarah Cannon Research Institute, Nashville, Tennessee; University of Illinois, Urbana Champaign, College of Medicine, Urbana, Illinois.
authors.forename: James A
authors.initials: JA
authors.lastname: Solomon
authors.affiliation: University of Central Florida, College of Medicine, Orlando, Florida.
authors.forename: John D
authors.initials: JD
authors.lastname: Hainsworth
authors.affiliation: Dermsurgery Associates, Houston, Texas.
authors.forename: Leonard
authors.initials: L
authors.lastname: Goldberg
authors.affiliation: Genentech Inc, South San Francisco, California.
authors.forename: Edward
authors.initials: E
authors.lastname: McKenna
authors.affiliation: Genentech Inc, South San Francisco, California.
authors.forename: Bann-mo
authors.initials: BM
authors.lastname: Day
authors.affiliation: Genentech Inc, South San Francisco, California.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Chen
authors.affiliation: Virginia G. Piper Cancer Center Clinical Trials at Scottsdale Healthcare, Scottsdale, Arizona.
authors.forename: Glen J
authors.initials: GJ
authors.lastname: Weiss
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000505:Alopecia / Q000139:chemically induced; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000556:secondary*; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000556:secondary; D003967:Diarrhea / Q000139:chemically induced; D018450:Disease Progression; D004408:Dysgeusia / Q000139:chemically induced; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013035:Spasm / Q000139:chemically induced; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000813:Anilides; D000970:Antineoplastic Agents; C538724:HhAntag691; D011725:Pyridines
keywords: AE; BCC; BCNS; ECOG; Eastern Cooperative Oncology Group; FDA; Hedgehog pathway inhibitor; ORR; RECIST; Response Evaluation Criteria in Solid Tumors; SMO; Smoothened; TEAE; US Food and Drug Administration; adverse event; basal cell carcinoma; basal cell nevus syndrome; expanded access; locally advanced; metastatic; objective response rate; treatment-emergent adverse event; vismodegib