Integrated Data From 2 Phase 3 Trials Of Active Cellular Immunotherapy With Sipuleucel-T In Advanced Prostate Cancer

Main Category: Prostate / Prostate Cancer
Also Included In: Urology / Nephrology;  Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 10 Aug 2009 - 2:00 PDT

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UroToday.com - In the online edition of Cancer, Dr. Higano and collaborators report on the use of Sipuleucel-T in the treatment of advanced prostate cancer (CaP). Sipuleucel-T is an autologous active cellular immunotherapy that stimulates an immune response against CaP. It consists of autologous peripheral blood mononuclear cells, including antigen-presenting cells (APCs) that have been activated in vitro with recombinant fusion protein composed of prostatic acid phosphatase.

Two randomized phase 3 clinical trials were performed that included 2 identically designed, randomized, double-blind, placebo-controlled studies; D9901 and D9902A. The combined trial analysis permits an assessment of the treatment effect and safety profile using a larger sample size. All participants had CaP with evidence of metastases, castrate levels of serum testosterone and at least 3 month survival expectancy. They all had evidence of disease progression either radiographically or by PSA progression. Participants were randomized to either Sipuleucel-T or placebo. Patients from both groups underwent a series of 3 leukapheresis at weeks 0, 2, and 4 followed 2 days later by infusion of Sipuleucel-T or placebo. The primary objective in both studies was to compare the time to disease progression.

In D9901, 127 patients were randomized to Sipuleucel-T (n=82) or placebo (n=45) from 2000 to 2001. A 31% reduction in the risk of disease progression and a 41% reduction in the risk of death were observed. In D9902A, patients were randomized to Sipuleucel-T (n=65) or placebo (n=33) and the time to disease progression was not statistically different between the two treatment groups. In the combined analysis, baseline characteristics were comparable between the 2 treatment arms. A PSA response rate of 4.8% was observed in the Sipuleucel-T group compared to 0% in the placebo group. The Sipuleucel-T patients had a 21% reduction in the risk of disease progression and a 33% reduction in the risk of death compared with men randomized to placebo. The median survival was 23.2 months for Sipuleucel-T and 18.9 months for placebo. The percentage of patients alive at 36 months was 33% for Sipuleucel-T and 15% for placebo.CD54 is an intracellular adhesion molecule upregulated on APCs during manufacture of Sipuleucel-T. Cumulative CD54 upregulation was strongly correlated with overall survival in the Sipuleucel-T arm. The overall incidence of adverse events was similar the two treatment arms.

Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, Provost N, Frohlich MW

Cancer. 2009 Jun 17. Epub ahead of print.
doi:10.1002/cncr.24429

Written by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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