Sipuleucel-T immunotherapy for castration-resistant prostate cancer

N Engl J Med. 2010 Jul 29;363(5):411-22. doi: 10.1056/NEJMoa1001294.

Abstract

Background: Sipuleucel-T, an autologous active cellular immunotherapy, has shown evidence of efficacy in reducing the risk of death among men with metastatic castration-resistant prostate cancer.

Methods: In this double-blind, placebo-controlled, multicenter phase 3 trial, we randomly assigned 512 patients in a 2:1 ratio to receive either sipuleucel-T (341 patients) or placebo (171 patients) administered intravenously every 2 weeks, for a total of three infusions. The primary end point was overall survival, analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum prostate-specific antigen (PSA) and lactate dehydrogenase.

Results: In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P=0.03). This reduction represented a 4.1-month improvement in median survival (25.8 months in the sipuleucel-T group vs. 21.7 months in the placebo group). The 36-month survival probability was 31.7% in the sipuleucel-T group versus 23.0% in the placebo group. The treatment effect was also observed with the use of an unadjusted Cox model and a log-rank test (hazard ratio, 0.77; 95% CI, 0.61 to 0.97; P=0.02) and after adjustment for use of docetaxel after the study therapy (hazard ratio, 0.78; 95% CI, 0.62 to 0.98; P=0.03). The time to objective disease progression was similar in the two study groups. Immune responses to the immunizing antigen were observed in patients who received sipuleucel-T. Adverse events that were more frequently reported in the sipuleucel-T group than in the placebo group included chills, fever, and headache.

Conclusions: The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer. No effect on the time to disease progression was observed. (Funded by Dendreon; ClinicalTrials.gov number, NCT00065442.)

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / therapeutic use
  • Antigen-Presenting Cells
  • Antineoplastic Agents / therapeutic use
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / therapeutic use*
  • Cell Culture Techniques
  • Combined Modality Therapy
  • Disease Progression
  • Double-Blind Method
  • Humans
  • Immunotherapy* / adverse effects
  • Infusions, Intravenous
  • Intercellular Adhesion Molecule-1 / adverse effects
  • Intercellular Adhesion Molecule-1 / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Prostatic Neoplasms / drug therapy
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / therapy*
  • Tissue Extracts / adverse effects
  • Tissue Extracts / therapeutic use*

Substances

  • Androgen Antagonists
  • Antineoplastic Agents
  • Cancer Vaccines
  • Tissue Extracts
  • Intercellular Adhesion Molecule-1
  • sipuleucel-T

Associated data

  • ClinicalTrials.gov/NCT00065442