title: GDC-0449 in patients with advanced chondrosarcomas: a French Sarcoma Group/US and French National Cancer Institute Single-Arm Phase II Collaborative Study.
abstract: BACKGROUND
  Pre-clinical data have suggested a therapeutic role of Hedgehog (Hh) pathway inhibitors in chondrosarcoma.
  
  
  METHODS
  This phase II trial included patients with progressive advanced chondrosarcoma. They received GDC-0449 150 mg/day (days 1-28, 28-day cycle). The primary end point was the 6-month clinical benefit rate (CBR) defined as the proportion of patients with non-progressive disease at 6 months. A 6-month CBR of 40% was considered as a reasonable objective to claim drug efficacy.
  
  
  RESULTS
  Between February 2011 and February 2012, 45 patients were included. Twenty had received prior chemotherapy. Thirty-nine were assessable for efficacy. The 6-month CBR was 25.6% (95% confidence interval 13.0-42.1). All stable patients had grade 1 or 2 conventional chondrosarcoma with documented progression within the 6 months before inclusion. All but one with available data also had overexpression of the Hh ligand. Median progression-free and overall survivals were 3.5 and 12.4 months, respectively. The most frequent adverse events were grade 1 or 2 myalgia, dysgeusia and alopecia.
  
  
  CONCLUSIONS
  GDC-0449 did not meet the primary end point of this trial. Results suggest some activity in a subset of patients with progressive grade 1 or 2 conventional chondrosarcoma. Further studies assessing its role in combination with chemotherapy are warranted.
  
  
  BACKGROUND
  NCT01267955.
authors.affiliation: Department of Medical Oncology, Institut Bergonié, Bordeaux.
authors.forename: A
authors.initials: A
authors.lastname: Italiano
authors.forename: A
authors.initials: A
authors.lastname: Le Cesne
authors.forename: C
authors.initials: C
authors.lastname: Bellera
authors.forename: S
authors.initials: S
authors.lastname: Piperno-Neumann
authors.forename: F
authors.initials: F
authors.lastname: Duffaud
authors.forename: N
authors.initials: N
authors.lastname: Penel
authors.forename: P
authors.initials: P
authors.lastname: Cassier
authors.forename: J
authors.initials: J
authors.lastname: Domont
authors.forename: N
authors.initials: N
authors.lastname: Takebe
authors.forename: M
authors.initials: M
authors.lastname: Kind
authors.forename: J-M
authors.initials: JM
authors.lastname: Coindre
authors.forename: J-Y
authors.initials: JY
authors.lastname: Blay
authors.forename: B
authors.initials: B
authors.lastname: Bui
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000008:administration & dosage*; D002813:Chondrosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000473:pathology*; D005260:Female; D005602:France; D015972:Gene Expression Regulation, Neoplastic; D053823:Hedgehog Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000008:administration & dosage*
chemical_list: D000813:Anilides; D053823:Hedgehog Proteins; C538724:HhAntag691; D011725:Pyridines
keywords: GDC-0449; Hedgehog pathway; chondrosarcoma; treatment