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.)
Kantoff
Philip W
PW
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA. philip_kantoff@dfci.harvard.edu
Higano
Celestia S
CS
Shore
Neal D
ND
Berger
E Roy
ER
Small
Eric J
EJ
Penson
David F
DF
Redfern
Charles H
CH
Ferrari
Anna C
AC
Dreicer
Robert
R
Sims
Robert B
RB
Xu
Yi
Y
Frohlich
Mark W
MW
Schellhammer
Paul F
PF
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D000938:Antigen-Presenting Cells; D000970:Antineoplastic Agents / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D018929:Cell Culture Techniques; D003131:Combined Modality Therapy; D018450:Disease Progression; D004311:Double-Blind Method; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D007262:Infusions, Intravenous; D018799:Intercellular Adhesion Molecule-1 / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D014020:Tissue Extracts / Q000009:adverse effects / Q000627:therapeutic use*
D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D019496:Cancer Vaccines; D014020:Tissue Extracts; D018799:Intercellular Adhesion Molecule-1; C511774:sipuleucel-T