Real-World Data With Sipuleucel-T Showcase Promising OS in mCRPC

Sipuleucel-T (Provenge) was associated with a median overall survival of 47.7 months in a subgroup of patients with asymptomatic or minimally invasive metastatic castration-resistant prostate cancer.

Celestia S. Higano, MD, FACP

Sipuleucel-T (Provenge) was associated with a median overall survival (OS) of 47.7 months in patients with asymptomatic or minimally invasive metastatic castration-resistant prostate cancer (mCRPC) when their baseline prostate-specific antigen (PSA) was ≤5.27 ng/mL, according to real-world results of the PROCEED registry that were published in Cancer.1,2

“The median survival of four years following treatment with Provenge is meaningful,” lead study author Celestia S. Higano, MD, FACP, professor, Division of Medical Oncology, Department of Medicine, University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, said in a press release. “PROCEED provides a real-world portrait of the expected OS after sipuleucel-T in mCRPC patients in the modern era of five additional life-prolonging agents.”

Sipuleucel-T was approved by the FDA in 2010 for the treatment of patients with asymptomatic or minimally symptomatic metastatic mCRPC, and is listed as a category 1 recommendation by the National Comprehensive Cancer Network.

In the multicenter, open-label, observational PROCEED registry, investigators enrolled 1976 patients with mCRPC who received sipuleucel-T between 2011 and 2014 in the everyday treatment setting. Patients underwent a 1.5 to 2.0× blood volume leukapheresis for antigen‐presenting cell isolation, followed by a sipuleucel‐T infusion 3 to 4 days later. Infusions were repeated in biweekly intervals for 3 infusions.

The median age was 72 years, and the median baseline PSA was 15.0 ng/mL. Moreover, 86.7% of patients were white and 11.6% were African American. Most patients had an ECOG performance status of 0 (66.5%) or 1 (30.0%). Some patients received prior therapy, including but not limited to abiraterone acetate (Zytiga; 8.3%), enzalutamide (Xtandi; 2.8%), docetaxel (11.3%), cabazitaxel (Jevtana; 1.7%), and radium-223 dichloride (Xofigo; 0.1%).

A total 1902 patients had ≥1 infusion of sipuleucel-T; 1248 (65.6%) patients were treated in oncology practices, while 654 (34.4%) received the treatment in urology practices. A total 79.1% of patients had sipuleucel-T at 140 community clinics, while the remainder received the therapy at 52 academic institutions. Central venous catheters were used in 891 patients (46.8%).

Investigators assessed OS, serious adverse events (AEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs), which included abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium-223 dichloride. Patients were followed and assessed every 3 months for ≥3 years or until death or withdrawal from the trial.

At a median follow-up of 46.6 months, results showed that the median OS was 30.7 months (95% CI, 28.6‐32.2 months). There were 1255 deaths, 964 (76.8%) of which died of disease progression; death or survival could not be established for 45 patients.

The median time from the first sipuleucel-T infusion to prostate cancer—related death was 42.7 months (95% CI, 39.4-46.2). Other causes of death were either unknown (12.3%), other (10.8%), a cardiac event (3.3%), a CVE (1.4%), and a new primary cancer (0.6%). More than 1 cause of death could be recorded for a patient.

Findings from a posthoc analysis showed that that the median OS was longer for patients in the lowest baseline PSA quartile (≤5.27 ng/mL) compared with those in the second (>5.27 to ≤15.08 ng/mL), third (>15.08 to ≤46 ng/mL), and fourth quartiles (>46 ng/mL), at 47.7 months (95% CI, 43.5‐50.7), 33.2 months (95% CI, 30.9‐35.5), 27.2 months (95% CI, 24.1‐29.8), and 18.4 months (95% CI, 15.9‐21.2), respectively. Moreover, the hazard ratios for each quartile versus the lowest quartile were 1.6 (95% CI, 1.3‐1.9), 2.0 (95% CI, 1.7‐2.4), and 3.0 (95% CI, 2.6‐3.6), respectively.

Additionally, data from a multivariable analysis showed that prognostic factors were independently associated with OS. These included time since diagnosis (HR, 0.72; 95% CI, 0.62&#8208;0.83; P <.001), lymph node only metastases (HR, 0.79; 95% CI, 0.63-0.99; P = .044), hemoglobin (HR, 0.87; 95% CI, 0.83-0.91; P <.001), PSA (HR, 1.22; 95% CI, 1.16-1.27; P <.001), ECOG performance status (HR, 1.22; 95% CI, 1.05-1.42; P = .009), age (HR, 1.30; 95% CI, 1.12-1.50; P <.001), visceral metastases (HR, 1.30; 95% CI, 0.95-1.78; P = .098), prior docetaxel/cabazitaxel (HR, 1.54; 95% CI, 1.25-1.90; P <.001), and prior abiraterone/enzalutamide (HR, 1.53; 95% CI, 1.16-1.27; P <.001).

Regarding safety, all-grade serious AEs occurred in 13.7% of patients and grade 3 to 5 AEs were in 9.2% of patients; the incidence of sipuleucel&#8208;T—related serious AEs was 3.9%. CVEs occurred in 2.8% of patients, and the rate per 100 person&#8208;years was 1.2 (95% CI, 0.9&#8208;1.6). Additionally, the CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results–Medicare database was 2.8%, and the rate per 100 person&#8208;years was 1.5 (95% CI, 1.4&#8208;1.7).

One or more of the ACIs were received by 77.1% of patients after receiving sipuleucel&#8208;T. In these patients, the 1- and 2-year treatment-free intervals were 32.5% and 17.4%, respectively. Moreover, 44% of patients with a PSA of <5.27 ng/mL did not receive any additional cancer treatments for ≥1 year. Of those patients, 95% were treated with frontline sipuleucel-T.

The PROCEED findings are consistent with a previous posthoc analysis of the phase III IMPACT trial in 2013, which also evaluated sipuleucel-T.3 Results of IMPACT showed that a lower baseline PSA level was associated with improved OS, and among those with a baseline PSA ≤22.1 ng/mL, the median OS was 41.3 months for those treated with sipuleucel-T compared with 28.3 months for those in the control arm.

“Median baseline PSA levels at mCRPC diagnosis have declined steadily since the approval of Provenge in 2010,” said Bruce A. Brown, MD, chief medical officer at Dendreon, the developer of sipuleucel-T. “Of the nearly 2000 patients enrolled in PROCEED between 2011 and 2014 a quarter had a PSA of <5.27 ng/mL, and these men lived much longer than those in the higher quartiles. It’s worth noting that the median baseline PSA levels observed in PROCEED are lower than those in the pivotal IMPACT trial and would likely be lower if PROCEED was enrolling today.”


  1. Higano CS, Armstrong AJ, Sartor AO, et al. Real&#8208;world outcomes of sipuleucel&#8208;T treatment in PROCEED, a prospective registry of men with metastatic castration&#8208;resistant prostate cancer [published online ahead of print September 4, 2019]. Cancer. doi: 10.1002/cncr.32445.
  2. Largest Real-World Study of Immunotherapy Shows Men with Advanced Prostate Cancer with Low PSA had a Median Survival of Nearly Four Years after Treatment with PROVENGE® (sipuleucel-T)[news release]. Seal Beach, CA: Dendreon Pharmaceuticals. Published September 4, 2019. Accessed September 4, 2019.
  3. Schellhammer PF, Chodak G, Whitmore JB, Sims R, Frohlich MW, Kantoff PW. Lower baseline prostate-specific antigen is associated with a greater overall survival benefit from sipuleucel-T in the Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial. Urology. 2013;81(6):1297-1302. doi: 10.1016/j.urology.2013.01.061.