Sipuleucel-T in the treatment of prostate cancer: an evidence-based review of its place in therapy

Abstract

Metastatic castration-resistant prostate cancer is the lethal form of cancer of the prostate. Five new agents that prolong survival in this group have emerged in the past 5 years, and sipuleucel-T is among them. Sipuleucel-T is the only immunotherapy shown to improve survival in prostate cancer. It is currently indicated in asymptomatic or mildly symptomatic patients, as it has never shown a direct cancer effect. This paper describes the process of creating the sipuleucel-T product from the manufacturing and patient aspects. It discusses the four placebo-controlled, randomized clinical trials (RCTs) of sipuleucel-T, focusing on survival and adverse events. There are three RCTs in metastatic castration-resistant prostate cancer, all of which showed improved overall survival without meaningful decreases in symptoms, tumor volumes, or prostate-specific antigen levels. One RCT in castration-sensitive, biochemically relapsed prostate cancer attempted to find a decrease in biochemical failure, but that endpoint was not reached. Adverse events in all four of these studies centered around cytokine release. This paper also reviews a Phase II study of sipuleucel-T given neoadjuvantly that speaks to its mechanism of action. Additionally, there is a registry study of sipuleucel-T that has been used to evaluate immunological parameters of the product in men ≥80 years of age and men who had previously been treated with palliative radiation. Attempts to find early markers of response to sipuleucel-T are described. Further ongoing studies that explore the efficacy of sipuleucel-T in combination with immune checkpoint inhibitors and second-generation hormonal therapies that are summarized. Finally, the only published economic analysis of sipuleucel-T is discussed.

Gene-based Interventions for Cancer Immunotherapy

“…Sipuleucel-T (Provenge), a dendritic cell-based vaccine for the treatment of metastatic castration-resistant prostate cancer, is the only example approved for use in humans. Its manufacture is done in a personalized manner, which involves the extraction of the patient's peripheral blood mononuclear cells (PBMCs) by leukapheresis, transport of the cells to Dendreon's facility (New Jersey, USA) for in vitro culture, maturation of DCs and loading with PA2024 (hybrid protein of GM-CSF and prostate-specific prostatic acid phosphatase, PAP) before returning the cells to the hospital where they will be administered to the patient [80].…”

What is the role of sipuleucel-T in the treatment of patients with advanced prostate cancer? An update on the evidence

“…Cells are then suspended in lactated ringer's solution and returned for infusion into the patient. The entire process takes about 4 weeks to complete [Graff and Chamberlain, 2015].…”

“…Phase IV analysis -PROCEED registry PROCEED is a phase IV registry established by the manufacturers of sipuleucel-T to evaluate patient characteristics and product parameters for patients treated with sipuleucel-T [Graff et al 2015].…”

Antiproliferative effect of a synthetic aptamer mimicking androgen response elements in the LNCaP cell line

“…5,6 Recently, Sipuleucel-T as a cancer vaccine and Radium-223 have been introduced for PCa refractory to hormone therapy. 7 Androgen receptors (ARs) (NR3C4; nuclear receptor subfamily 3, group C, member 4) have a crucial role in the development, function and homeostasis of PCa cells. ARs can be activated as a transcription factor via binding to androgen hormones (either testosterone or dihydrotestosterone).…”