Sipuleucel-T, is an autologous cellular immunotherapy originally indicated for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer patients. In the IMPACT study this treatment has demonstrated a 22.5% reduction in risk of death when compared to placebo and was generally well-tolerated2. The results of a small study suggested that cytolytic T cell responses may correlate with overall survival3. Furthermore, in localized prostate cancer patients, neoadjuvant Sipuleucel-T has been shown to increase cytotoxic T-cell infiltration at the tumor rim4.
In the ProVent study (NCT 03686683) the primary goal is to determine if Sipuleucel-T will decrease the development of histopathologic progression in subsequent prostate biopsies that patients on active surveillance undergo. This is an open-label, phase 3 multicenter trial comparing Sipuleucel-T to active surveillance in patients with newly-diagnosed localized, low-and favorable intermediate-risk prostate cancer. The study design is demonstrated in figure 1. The goal of the study is to enroll at least 450 patients over a period of 1 year. Eligible patients will include those with International Society of Urological Pathology (ISUP) Grade Group 1 (Gleason 3+3, >=3 positive cores, or 1 core positive with >=50% cancer involvement from a systematic biopsy) or ISUP grade group 2 (Gleason 3+4, <50% of cores positive from systematic biopsy), diagnosed within the previous 12 months. Patients will need to have a life expectancy of at least 10 years and be candidate for primary curative therapy if prostate cancer progression occurs. Patients will be randomized in a ratio of 2:1 to receive Sipuleucel-T or undergo active surveillance. In the Sipuleucel-T arm, patients will receive 3 biweekly infusions and be followed for immune responses. Both groups will be followed on a regular basis every 6 month, for a minimum of 3 years. Follow-up will entail PSA, clinical disease changes, prostate biopsies (between 12-18 months, and between 33-39 months). All biopsies will be centrally assessed for histological reclassification relative to baseline.
Figure 1 – ProVent trial design:
The primary end-point of the study is the proportion of patients without an ISUP upgrade at year 3. Lastly, secondary endpoints will include: the number of patients with subsequent prostate cancer treatment, patient-reported outcomes, and safety. Additionally, exploratory end points will include genomic analysis and prostate tissue immunohistochemistry.
The study is currently actively recruiting patients.
Presented by: Neal Shore, Carolina Urologic Research Center
1. Klotz L, et al. J Clin Oncol 2015
2. Kantoff et al. New Engl J Med 2010
3. Antonarakis et al. Clin Cancer Res 2018
4. Fong et al. J Natl Cancer Inst 2014
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona