Randomized Trial of Autologous Cellular Immunotherapy with Sipuleucel-T in Androgen-Dependent Prostate Cancer

Abstract

Purpose: Sipuleucel-T, an autologous cellular immunotherapy, was investigated in a randomized, double-blind, controlled trial to determine its biologic activity in androgen-dependent prostate cancer (ADPC).Experimental Design: Patients with prostate cancer detectable by serum prostate-specific antigen (PSA) following radical prostatectomy received 3 to 4 months of androgen suppression therapy, and were then randomized (2:1) to receive sipuleucel-T (n ¼ 117) or control (n ¼ 59). The primary endpoint was time to biochemical failure (BF) defined as serum PSA 3.0 ng/mL. PSA doubling time (PSADT), time to distant failure, immune response, and safety were also evaluated.Results: Median time to BF was 18.0 months for sipuleucel-T and 15.4 months for control (HR ¼ 0.936, P ¼ 0.737). Sipuleucel-T patients had a 48% increase in PSADT following testosterone recovery (155 vs. 105 days, P ¼ 0.038). With only 16% of patients having developed distant failure, the treatment effect favored sipuleucel-T (HR ¼ 0.728, P ¼ 0.421). The most frequent adverse events in sipuleucel-T patients were fatigue, chills, and pyrexia. Immune responses to the immunizing antigen were greater in sipuleucel-T patients at Weeks 4 and 13 (P < 0.001, all) and were sustained prior to boosting as measured in a subset of patients a median of 22.6 months (range: 14.3-67.3 months) following randomization.Conclusions: No significant difference in time to BF could be shown. The finding of increased PSADT in the sipuleucel-T arm is consistent with its biologic activity in ADPC. Long-term follow-up will be necessary to determine if clinically important events, such as distant failure, are affected by therapy. Treatment was generally well tolerated. Clin Cancer Res; 17(13); 4558-67. Ó2011 AACR.

Dendritic Cell–Based Immunotherapy: State of the Art and Beyond

“…Grade 3 or 4 treatment-related toxicity is extremely uncommon when DC vaccination is given as monotherapy (15). These data are confirmed by the available data from phase III trials where DC vaccination is compared with placebo (16)(17)(18)(19). Therefore, DC vaccination is considered safe and expected to preserve the quality of life in cancer patients.…”

Vaccination with Antigen-Transfected, NKT Cell Ligand–Loaded, Human Cells Elicits Robust In Situ Immune Responses by Dendritic Cells

“…Recently, Sipuleucel-T (Provenge, Dendreon Corp.), an autologous DC vaccine for patients with prostate cancer that uses prostatic acid phosphatase fused with GM-CSF, showed biologic activity and prolonged median survival in phase III vaccine trials and became the first antigen-specific, cellbased immunotherapy to receive U.S. Food and Drug Administration (FDA) approval (19). This promising initial outcome with autologous cellular therapy will require long-term follow-up but may herald a new era of prolonged overall cancer survival resulting from tumor antigen-specific T-cell responses.…”

Sipuleucel-T for the treatment of metastatic prostate cancer

“…time to biochemical failure, they did find a 48% increase in PSADT in the sipuleucel-T arm compared with placebo (p = 0.038). 60 A second analysis of the same patient population also demonstrated no significant difference in quality-of-life between the sipuleucel-T arm and the placebo arm. 61 Understanding of clinically important outcomes, such as distant failure, will require long-term follow-up.…”