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.

SUBMITTER: Graff JN 

PROVIDER: S-EPMC4279604 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature