title: Phase II randomized study of figitumumab plus docetaxel and docetaxel alone with crossover for metastatic castration-resistant prostate cancer.
abstract: Figitumumab is a human IgG2 monoclonal antibody targeting insulin-like growth factor 1 receptor (IGF-1R), with antitumor activity in prostate cancer. This phase II trial randomized chemotherapy-naïve men with progressing castration-resistant prostate cancer to receive figitumumab every 3 weeks with docetaxel/prednisone (Arm A) or docetaxel/prednisone alone (Arm B1). At progression on Arm B1, patients could cross over to the combination (Arm B2).
  
  
  
  Prostate-specific antigen (PSA) response was the primary endpoint; response assessment on the two arms was noncomparative and tested separately; H0 = 0.45 versus HA = 0.60 (α = 0.05; β = 0.09) for Arm A; H0 = 0.05 versus HA = 0.20 (α = 0.05, β = 0.10) for Arm B2. A comparison of progression-free survival (PFS) on Arms A and B1 was planned.
  
  
  
  A total of 204 patients were randomized and 199 treated (Arm A: 97; Arm B1: 102); 37 patients crossed over to Arm B2 (median number of cycles started: Arm A = 8; B1 = 8; B2 = 4). PSA responses occurred in 52% and 60% of Arms A and B1, respectively; the primary PSA response objective in Arm A was not met. Median PFS was 4.9 and 7.9 months, respectively (HR = 1.44; 95% confidence interval, 1.06-1.96). PSA response rate was 28% in Arm B2. The figitumumab combination appeared more toxic, with more treatment-related grade 3/4 adverse events (75% vs. 56%), particularly hyperglycemia, diarrhea, and asthenia, as well as treatment-related serious adverse events (41% vs. 15%), and all-causality grade 5 adverse events (18% vs. 8%).
  
  
  
  IGF-1R targeting may merit further evaluation in this disease in selected populations, but combination with docetaxel is not recommended.
authors.affiliation: Authors' Affiliations: Royal Marsden NHS Foundation Trust and The Institute of Cancer Research UK, Sutton; Institut Català d'Oncologia, L'Hospitalet, Barcelona; University of Surrey, Surrey, United Kingdom; Yale University Cancer Center, New Haven; Centre Hospitalier de l'Universite de Montreal, Montreal; A Coruña University Hospital, A Coruña, Spain; Kantonsspital St. Gallen, St. Gallen, Switzerland; Fox Chase Cancer Center, Philadelphia, Pennsylvania; Pfizer Inc, Groton, Connecticut; and Lady Davis Institute for Medical Research, Jewish General Hospital and McGill University, Montreal, Quebec, Canada.
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
authors.forename: Josep M
authors.initials: JM
authors.lastname: Piulats
authors.forename: Hardev S
authors.initials: HS
authors.lastname: Pandha
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Petrylak
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.forename: Luis Miguel A
authors.initials: LM
authors.lastname: Aparicio
authors.forename: Shahneen K
authors.initials: SK
authors.lastname: Sandhu
authors.forename: Peter
authors.initials: P
authors.lastname: Fong
authors.forename: Silke
authors.initials: S
authors.lastname: Gillessen
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hudes
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Judith
authors.initials: J
authors.lastname: Scranton
authors.forename: Michael N
authors.initials: MN
authors.lastname: Pollak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000276:immunology / Q000627:therapeutic use; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D000911:Antibodies, Monoclonal; D043823:Taxoids; D000077143:Docetaxel; D017526:Receptor, IGF Type 1; C525021:figitumumab