title: The 12-month analysis from Basal Cell Carcinoma Outcomes with LDE225 Treatment (BOLT): A phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma.
abstract: BACKGROUND
  The hedgehog pathway inhibitor sonidegib demonstrated meaningful tumor shrinkage in more than 90% of patients with locally advanced basal cell carcinoma (BCC) or metastatic BCC in the BCC Outcomes with LDE225 Treatment study.
  
  
  OBJECTIVE
  This report provides long-term follow-up data collected up to 12 months after the last patient was randomized.
  
  
  METHODS
  In this multicenter, randomized, double-blind phase II study, patients were randomized 1:2 to sonidegib 200 or 800 mg. The primary end point was objective response rate assessed by central review.
  
  
  RESULTS
  Objective response rates in the 200- and 800-mg arms were 57.6% and 43.8% in locally advanced BCC and 7.7% and 17.4% in metastatic BCC, respectively. Among the 94 patients with locally advanced BCC who responded, only 18 progressed or died and more than 50% had responses lasting longer than 6 months. In addition, 4 of 5 responders with metastatic BCC maintained an objective response. Grade 3/4 adverse events and those leading to discontinuation were less frequent with sonidegib 200 versus 800 mg (38.0% vs 59.3%; 27.8% vs 37.3%, respectively).
  
  
  CONCLUSIONS
  No placebo or comparator arms were used because sonidegib demonstrated efficacy in advanced BCC in a phase I study, and the hedgehog pathway inhibitor vismodegib was not yet approved.
  
  
  CONCLUSIONS
  With longer follow-up, sonidegib demonstrated sustained tumor responses in patients with advanced BCC.
authors.affiliation: UniversitätsSpital Zürich-Skin Cancer Center, University Hospital, Zürich, Switzerland. Electronic address: reinhard.dummer@usz.ch.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dummer
authors.affiliation: Royal North Shore Hospital, Sydney, Australia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Guminski
authors.affiliation: Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gutzmer
authors.affiliation: Sint-Augustinus Ziekenhuis, Antwerp, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Dirix
authors.affiliation: Division of Medical Oncology, School of Medicine, University of Colorado, Aurora, Colorado.
authors.forename: Karl D
authors.initials: KD
authors.lastname: Lewis
authors.affiliation: Anti Cancer Institute, Léon Bérard, Lyon, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Combemale
authors.affiliation: Glasgow Royal Infirmary, Glasgow, United Kingdom.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Herd
authors.affiliation: University Hospital Jena, Jena, Germany; SRH Wald-Klinikum Gera GmbH, Gera, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kaatz
authors.affiliation: University Medical Center Mainz, Mainz, Germany.
authors.forename: Carmen
authors.initials: C
authors.lastname: Loquai
authors.affiliation: Department of Dermatology, Andreas Sygros Hospital, University of Athens, Athens, Greece.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Stratigos
authors.affiliation: Fachklinik Hornheide, Münster, Germany.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Schulze
authors.affiliation: Northern Centre for Cancer Care, Freeman Hospital, Newcastle upon Tyne, United Kingdom.
authors.forename: Ruth
authors.initials: R
authors.lastname: Plummer
authors.affiliation: Novartis Pharma AG, Oncology Global Development, Basel, Switzerland.
authors.forename: Sven
authors.initials: S
authors.lastname: Gogov
authors.affiliation: Novartis Pharma AG, Oncology Global Development, Basel, Switzerland.
authors.forename: Celine
authors.initials: C
authors.lastname: Pallaud
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Tingting
authors.initials: T
authors.lastname: Yi
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Manisha
authors.initials: M
authors.lastname: Mone
authors.affiliation: Stanford University School of Medicine, Redwood City, California.
authors.forename: Anne Lynn S
authors.initials: AL
authors.lastname: Chang
authors.affiliation: Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Cornélis
authors.affiliation: Winship Cancer Institute at Emory University, Atlanta, Georgia.
authors.forename: Ragini
authors.initials: R
authors.lastname: Kudchadkar
authors.affiliation: Dermatologikum Berlin, Berlin, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Trefzer
authors.affiliation: Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.
authors.forename: John T
authors.initials: JT
authors.lastname: Lear
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
authors.forename: Dalila
authors.initials: D
authors.lastname: Sellami
authors.affiliation: Departments of Dermatology and Head and Neck Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Migden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002280:Basal Cell Carcinoma / Q000188:drug therapy* / Q000556:secondary; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000072086:Smoothened Receptor / Q000037:antagonists & inhibitors; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D011725:Pyridines; D000072086:Smoothened Receptor; C561435:sonidegib
keywords: Basal Cell Carcinoma Outcomes with LDE225 Treatment study; advanced basal cell carcinoma; hedgehog pathway inhibitor; locally advanced basal cell carcinoma; metastatic basal cell carcinoma; sonidegib