title: Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer.
abstract: OBJECTIVE
  Sipuleucel-T (APC8015) is an investigational immunotherapy product designed to stimulate T-cell immunity against prostatic acid phosphatase. A phase III study was undertaken to evaluate the safety and efficacy of sipuleucel-T in a placebo-controlled study.
  
  
  METHODS
  A total of 127 patients with asymptomatic metastatic hormone refractory prostate cancer (HRPC) were randomly assigned in a 2:1 ratio to receive three infusions of sipuleucel-T (n = 82) or placebo (n = 45) every 2 weeks. On disease progression, placebo patients could receive APC8015F, a product made with frozen leukapheresis cells.
  
  
  RESULTS
  Of the 127 patients, 115 patients had progressive disease at the time of data analysis, and all patients were followed for survival for 36 months. The median for time to disease progression (TTP) for sipuleucel-T was 11.7 weeks compared with 10.0 weeks for placebo (P = .052, log-rank; hazard ratio [HR], 1.45; 95%CI, 0.99 to 2.11). Median survival was 25.9 months for sipuleucel-T and 21.4 months for placebo (P = .01, log-rank; HR, 1.70; 95%CI, 1.13 to 2.56). Treatment remained a strong independent predictor of overall survival after adjusting for prognostic factors using a Cox multivariable regression model (P = .002, Wald test; HR, 2.12; 95%CI, 1.31 to 3.44). The median ratio of T-cell stimulation at 8 weeks to pretreatment was eight-fold higher in sipuleucel-T-treated patients (16.9 v 1.99; P < .001). Sipuleucel-T therapy was well tolerated.
  
  
  CONCLUSIONS
  While the improvement in the primary end point TTP did not achieve statistical significance, this study suggests that sipuleucel-T may provide a survival advantage to asymptomatic HRPC patients. Supportive studies are underway.
authors.affiliation: UCSF Comprehensive Cancer Center, University of California, San Francisco, 1600 Divisadero St, Box 1711, San Francisco, CA 94115, USA. smalle@medicine.ucsf.edu
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.forename: Paul F
authors.initials: PF
authors.lastname: Schellhammer
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.forename: Charles H
authors.initials: CH
authors.lastname: Redfern
authors.forename: John J
authors.initials: JJ
authors.lastname: Nemunaitis
authors.forename: Frank H
authors.initials: FH
authors.lastname: Valone
authors.forename: Suleman S
authors.initials: SS
authors.lastname: Verjee
authors.forename: Lori A
authors.initials: LA
authors.lastname: Jones
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hershberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000628:therapy*; D016019:Survival Analysis; D014020:Tissue Extracts / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D014020:Tissue Extracts; C511774:sipuleucel-T