Real‐world outcomes of sipuleucel‐T treatment in PROCEED, a prospective registry of men with metastatic castration‐resistant prostate cancer

Abstract

BACKGROUND: PROCEED (), a large registry, evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). METHODS: PROCEED enrolled mCRPC patients receiving three biweekly sipuleucel-T infusions. Assessments included: overall survival (OS); serious adverse events (SAEs); cerebrovascular events (CVEs); and anticancer interventions (ACIs). Follow-up was ≥3 years, until death, or study withdrawal. RESULTS: 1976 patients (2011–2017) were followed for 46.6 months (median). Median age was 72 years and baseline median prostate-specific antigen was 15.0 ng/ml. 86.7% were Caucasians and 11.6% African American. 1902 patients had ≥1 sipuleucel-T infusion. Median OS was 30.7 (95% confidence interval [CI]: 28.6–32.2) months. Known prognostic factors were independently associated with OS on multivariable analysis. 1255 patients died, 964 (76.8%) from prostate cancer (PC) progression. Median time from first infusion to PC death was 42.7 (95% CI: 39.4–46.2) months. Incidence of sipuleucel-T-related SAEs was 3.9%. Incidence of CVEs was 2.8% and the rate per 100 person-years was 1.2 (95% CI: 0.9–1.6). CVE incidence among 11,972 mCRPC patients from the SEER-Medicare database was 2.8%; 1.5 [95% CI 1.4–1.7]/100 person-years. 77.7% of patients received ≥1 ACI (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium-223) after sipuleucel-T; 32.5% and 17.4% of patients experienced a 1- and 2-year treatment-free interval, respectively. CONCLUSIONS: PROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. Safety and tolerability of sipuleucel-T in PROCEED was consistent with previous findings.

Survival of African-American and Caucasian men after sipuleucel-T immunotherapy: outcomes from the PROCEED registry

“…PROCEED was a multicenter, open-label, observational registry in mCRPC patients who received sipuleucel-T, whose primary outcomes have been described previously [4]. Patients were treated at academic and community sites in urology and oncology clinics, from January 27, 2011 to January 17, 2017 [25].…”

“…Sample size (described previously) was chosen to address the primary registry endpoint, which was to assess the cerebrovascular event (CVE) rate [4]. Originally set at 1500 patients it was later increased to 1900 to allow for 4500 person-years of follow-up provided the observed CVE incidence rate was <2.8 per 100 patient-years [4].…”

“…The objectives of the analyses presented here are to explore the observations of a difference in survival outcomes between races given the identification of race as an important factor in the multivariate analysis model presented in the primary paper [4], which further describes the outcomes related to the prespecified study objectives of quantifying both the risk of CVEs and survival in all subjects.…”

“…Safety in PROCEED was assessed by recording serious adverse events (SAEs) using MedDRA version 19.1 (for greater details, please see Higano et al) [4].…”

“…Sipuleucel-T improved median overall survival (OS) by 4.1 months versus placebo in the pivotal IMPACT trial (NCT00065442), with a separate post hoc analysis demonstrating a 13-month OS benefit in those with prostate-specific antigen (PSA) levels below the median of 22.1 ng/mL at treatment start [2,3]. In a contemporary real-world setting of care, data from the PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED; NCT01306890) found that mCRPC patients treated with sipuleucel-T had a median OS of 30.7 months; with a median follow-up of 46.6 months and an OS of 47.7 months (95% confidence interval [CI], 43.5-50.7 months) in the lowest baseline PSA quartile (≤5.27 ng/mL) [4].…”