Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer.

Abstract

BACKGROUND:

Sipuleucel-T is an investigational active cellular immunotherapy product designed to stimulate an immune response against prostate cancer. The safety and efficacy of sipuleucel-T was evaluated in 2 identically designed, randomized, double-blind, placebo-controlled trials (D9901 and D9902A) conducted in men with advanced prostate cancer.

METHODS:

A total of 225 patients were randomized in D9901 or D9902A to sipuleucel-T (n = 147) or placebo (n = 78), given as 3 intravenous infusions approximately 2 weeks apart. Patients were followed for survival until death or a prespecified cutoff of 36 months after randomization.

RESULTS:

In the integrated analysis of D9901 and D9902A, patients randomized to sipuleucel-T demonstrated a 33% reduction in the risk of death (hazard ratio, 1.50; 95% confidence interval, 1.10-2.05; P = .011; log-rank). The treatment effect remained strong after performing adjustments for imbalances in baseline prognostic factors, poststudy treatment chemotherapy use, and non-prostate cancer-related deaths. Additional support for the activity of sipuleucel-T is provided by the correlation between a measure of the product's potency, CD54 up-regulation, and overall survival. The most common adverse events associated with treatment were chills, pyrexia, headache, asthenia, dyspnea, vomiting, and tremor. These events were primarily grade 1 and 2, with durations of 1 to 2 days.

CONCLUSIONS:

The integrated results of D9901 and D9902A demonstrate a survival benefit for patients treated with sipuleucel-T compared with those treated with placebo. The generally modest toxicity profile, coupled with the survival benefit, suggests a favorable risk-benefit ratio for sipuleucel-T in patients with advanced prostate cancer.

• Authors: Celestia S Higano, Paul F Schellhammer, Eric J Small, Patrick A Burch, John Nemunaitis, Lianng Yuh, Nicole Provost, Mark W Frohlich
• Journal: Cancer (Cancer) Vol. 115 Issue 16 Pg. 3670-9 (Aug 15 2009) ISSN: 0008-543X [Print] United States
• PMID: 19536890 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Cancer Vaccines
• Placebos
• Tissue Extracts
• sipuleucel-T

Topics

• Adenocarcinoma (pathology, therapy)
• Aged
• Aged, 80 and over
• Cancer Vaccines (therapeutic use)
• Disease Progression
• Double-Blind Method
• Humans
• Immunity, Active
• Male
• Middle Aged
• Neoplasm Metastasis
• Placebos
• Prostatic Neoplasms (pathology, therapy)
• Time Factors
• Tissue Extracts (adverse effects, therapeutic use)