Sipuleucel T immunotherapy for castration resistant prostate cancer.
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.
The New England journal of medicine