Sipuleucel-T immunotherapy for castration-resistant prostate cancer
Philip W Kantoff, Celestia S Higano, Neal D Shore, E Roy Berger, Eric J Small, David F Penson, Charles H Redfern, Anna C Ferrari, Robert Dreicer, Robert B Sims, Yi Xu, Mark W Frohlich, Paul F Schellhammer, IMPACT Study Investigators, T Ahmed, A Amin, J Arseneau, N Barth, G Bernstein, B Bracken, P Burch, V Caggiano, J Chin, G Chodak, F Chu, J Corman, B Curti, N Dawson, J F Deeken, T Dubernet, M Fishman, R Flanigan, F Gailani, L Garbo, T Gardner, E Gelmann, D George, T Godfrey, L Gomella, M Guerra, S Hall, J Hanson, R Israeli, E Jancis, M A S Jewett, V Kassabian, J Katz, L Klotz, K Koeneman, H Koh, R Kratzke, R Lance, J Lech, L Leichman, R Lemon, J Liang, J Libertino, M Lilly, I Malik, S E Martin, J McCaffrey, D McLeod, D McNeel, B Miles, M Murdock, C Nabhan, J Nemunaitis, D Notter, A Pantuck, P Perrotte, D Pessis, D Petrylak, J Polikoff, P Pommerville, S Ramanathan, M Rarick, J Richards, R Rifkin, N Rohatgi, R Rosenbluth, R Santucci, A Sayegh, J Seigne, I Shapira, N Shedhadeh, D Shepherd, S Sridhar, R Stephenson, C Teigland, N Thaker, J Vacirca, L Villa Jr, N Vogelzang, M Wertheim, J H Wolff, R Wurzel, C Yang, J Young, Philip W Kantoff, Celestia S Higano, Neal D Shore, E Roy Berger, Eric J Small, David F Penson, Charles H Redfern, Anna C Ferrari, Robert Dreicer, Robert B Sims, Yi Xu, Mark W Frohlich, Paul F Schellhammer, IMPACT Study Investigators, T Ahmed, A Amin, J Arseneau, N Barth, G Bernstein, B Bracken, P Burch, V Caggiano, J Chin, G Chodak, F Chu, J Corman, B Curti, N Dawson, J F Deeken, T Dubernet, M Fishman, R Flanigan, F Gailani, L Garbo, T Gardner, E Gelmann, D George, T Godfrey, L Gomella, M Guerra, S Hall, J Hanson, R Israeli, E Jancis, M A S Jewett, V Kassabian, J Katz, L Klotz, K Koeneman, H Koh, R Kratzke, R Lance, J Lech, L Leichman, R Lemon, J Liang, J Libertino, M Lilly, I Malik, S E Martin, J McCaffrey, D McLeod, D McNeel, B Miles, M Murdock, C Nabhan, J Nemunaitis, D Notter, A Pantuck, P Perrotte, D Pessis, D Petrylak, J Polikoff, P Pommerville, S Ramanathan, M Rarick, J Richards, R Rifkin, N Rohatgi, R Rosenbluth, R Santucci, A Sayegh, J Seigne, I Shapira, N Shedhadeh, D Shepherd, S Sridhar, R Stephenson, C Teigland, N Thaker, J Vacirca, L Villa Jr, N Vogelzang, M Wertheim, J H Wolff, R Wurzel, C Yang, J Young
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.)
Source: PubMed