title: Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer.
abstract: BACKGROUND
  Sipuleucel-T is an investigational active cellular immunotherapy product designed to stimulate an immune response against prostate cancer. The safety and efficacy of sipuleucel-T was evaluated in 2 identically designed, randomized, double-blind, placebo-controlled trials (D9901 and D9902A) conducted in men with advanced prostate cancer.
  
  
  METHODS
  A total of 225 patients were randomized in D9901 or D9902A to sipuleucel-T (n = 147) or placebo (n = 78), given as 3 intravenous infusions approximately 2 weeks apart. Patients were followed for survival until death or a prespecified cutoff of 36 months after randomization.
  
  
  RESULTS
  In the integrated analysis of D9901 and D9902A, patients randomized to sipuleucel-T demonstrated a 33% reduction in the risk of death (hazard ratio, 1.50; 95% confidence interval, 1.10-2.05; P = .011; log-rank). The treatment effect remained strong after performing adjustments for imbalances in baseline prognostic factors, poststudy treatment chemotherapy use, and non-prostate cancer-related deaths. Additional support for the activity of sipuleucel-T is provided by the correlation between a measure of the product's potency, CD54 up-regulation, and overall survival. The most common adverse events associated with treatment were chills, pyrexia, headache, asthenia, dyspnea, vomiting, and tremor. These events were primarily grade 1 and 2, with durations of 1 to 2 days.
  
  
  CONCLUSIONS
  The integrated results of D9901 and D9902A demonstrate a survival benefit for patients treated with sipuleucel-T compared with those treated with placebo. The generally modest toxicity profile, coupled with the survival benefit, suggests a favorable risk-benefit ratio for sipuleucel-T in patients with advanced prostate cancer.
authors.affiliation: Department of Oncology and Urology, University of Washington, Seattle, WA, USA. thigano@u.washington.edu
authors.forename: Celestia S
authors.initials: CS
authors.lastname: Higano
authors.forename: Paul F
authors.initials: PF
authors.lastname: Schellhammer
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Burch
authors.forename: John
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: Lianng
authors.initials: L
authors.lastname: Yuh
authors.forename: Nicole
authors.initials: N
authors.lastname: Provost
authors.forename: Mark W
authors.initials: MW
authors.lastname: Frohlich
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D006801:Humans; D007110:Immunity, Active; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010919:Placebos; D011471:Prostatic Neoplasms / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D014020:Tissue Extracts / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D019496:Cancer Vaccines; D010919:Placebos; D014020:Tissue Extracts; C511774:sipuleucel-T