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 Ferrari, Robert Dreicer, Robert B. Sims, Yi Xu, Mark W. Frohlich, Paul F. Schellhammer

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)411-422
Number of pages12
JournalNew England Journal of Medicine
Volume363
Issue number5
DOIs
StatePublished - Jul 29 2010

Fingerprint

Castration
Immunotherapy
Prostatic Neoplasms
Placebos
Survival
docetaxel
Confidence Intervals
Proportional Hazards Models
Disease Progression
Active Immunotherapy
Chills
sipuleucel-T
Prostate-Specific Antigen
L-Lactate Dehydrogenase
Headache
Fever
Antigens
Therapeutics
Serum

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Kantoff, P. W., Higano, C. S., Shore, N. D., Berger, E. R., Small, E. J., Penson, D. F., ... Schellhammer, P. F. (2010). Sipuleucel-T immunotherapy for castration-resistant prostate cancer. New England Journal of Medicine, 363(5), 411-422. https://doi.org/10.1056/NEJMoa1001294
Kantoff, Philip W. ; Higano, Celestia S. ; Shore, Neal D. ; Berger, E. Roy ; Small, Eric J. ; Penson, David F. ; Redfern, Charles H. ; Ferrari, Anna ; Dreicer, Robert ; Sims, Robert B. ; Xu, Yi ; Frohlich, Mark W. ; Schellhammer, Paul F. / Sipuleucel-T immunotherapy for castration-resistant prostate cancer. In: New England Journal of Medicine. 2010 ; Vol. 363, No. 5. pp. 411-422.
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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.",
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Kantoff, PW, Higano, CS, Shore, ND, Berger, ER, Small, EJ, Penson, DF, Redfern, CH, Ferrari, A, Dreicer, R, Sims, RB, Xu, Y, Frohlich, MW & Schellhammer, PF 2010, 'Sipuleucel-T immunotherapy for castration-resistant prostate cancer', New England Journal of Medicine, vol. 363, no. 5, pp. 411-422. https://doi.org/10.1056/NEJMoa1001294

Sipuleucel-T immunotherapy for castration-resistant prostate cancer. / Kantoff, Philip W.; Higano, Celestia S.; Shore, Neal D.; Berger, E. Roy; Small, Eric J.; Penson, David F.; Redfern, Charles H.; Ferrari, Anna; Dreicer, Robert; Sims, Robert B.; Xu, Yi; Frohlich, Mark W.; Schellhammer, Paul F.

In: New England Journal of Medicine, Vol. 363, No. 5, 29.07.2010, p. 411-422.

Research output: Contribution to journalArticle

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T1 - Sipuleucel-T immunotherapy for castration-resistant prostate cancer

AU - Kantoff, Philip W.

AU - Higano, Celestia S.

AU - Shore, Neal D.

AU - Berger, E. Roy

AU - Small, Eric J.

AU - Penson, David F.

AU - Redfern, Charles H.

AU - Ferrari, Anna

AU - Dreicer, Robert

AU - Sims, Robert B.

AU - Xu, Yi

AU - Frohlich, Mark W.

AU - Schellhammer, Paul F.

PY - 2010/7/29

Y1 - 2010/7/29

N2 - 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.

AB - 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.

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Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. New England Journal of Medicine. 2010 Jul 29;363(5):411-422. https://doi.org/10.1056/NEJMoa1001294