SUO 2018: ProVent: A Phase 3 Study of Sipuleucel-T Therapy in Subjects with Localized Prostate Cancer Followed by Active Surveillance

Phoenix, Arizona (UroToday.com) Differentiating between low grade prostate cancer that will remain indolent to one that will progress is quite challenging. The goal of active surveillance is to reduce overtreatment while retaining the option of treating patients who develop high-risk features. Radical definitive treatment with either radical prostatectomy or radiation therapy although effective, is associated with significant short and long-term side effects. These include sexual dysfunction, urinary incontinence and bowel issues.  Active surveillance is increasingly accepted as a treatment option for low- and favorable intermediate-risk prostate cancer. However, within 3 years, 30% of patients on active surveillance will have either an histological upgrade or have chosen treatment for other reasons1. To date, there has been no approval of any treatments in the active surveillance space.

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.

UroToday ProVent trial design
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

References:
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
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