ASCO 2018: Sipuleucel-T OS and Clinical Outcomes by Baseline PSA Quartiles in Patients with mCRPC: PROCEED Registry

Chicago, IL ( Sipuleucel-T is an autologous cellular immunotherapy for asymptomatic/minimally symptomatic men with metastatic castration-resistant prostate cancer (mCRPC). The seminal phase III clinical trial leading to FDA approval of Sipuleucel-T was the IMPACT trial, randomizing 512 men with mCRPC in a 2:1 ratio to receive Sipuleucel-T (n=341) or placebo (n=171)1. The primary endpoint was overall survival (OS), analyzed by means of a stratified Cox regression model adjusted for baseline levels of serum PSA and lactate dehydrogenase. In the sipuleucel-T group, there was a relative reduction of 22% in the risk of death as compared with the placebo group (HR 0.78, 95% CI 0.61-0.98), corresponding to a 4.1 month improvement in median survival (25.8 months vs. 21.7 months). The treatment effect was also observed after adjustment for use of docetaxel after the study therapy (HR 0.78, 95%CI 0.62-0.98). 

In a post-hoc analysis of the IMPACT trial patients assessing the prognostic and predictive value of baseline variables, PSA was the strongest baseline predictor of OS2. Interestingly, the sipuleucel-T treatment effect appeared greater with decreasing baseline PSA. The OS HR for patients in the lowest baseline PSA quartile (≤22.1 ng/mL) was 0.51 (95%CI 0.31-0.85) compared with 0.84 (95%CI 0.55-1.29) for patients in the highest PSA quartile (>134 ng/mL). The estimated improvement in median OS varied from 13.0 months in the lowest baseline PSA quartile to 2.8 months in the highest quartile, whereas the estimated 3-year OS in the lowest PSA quartile was 62.6% for sipuleucel-T patients and 41.6% for control patients. As such, the purpose of the study presented by Oliver Sartor, MD, and colleagues at ASCO 2018 was to analyze and potentially validate the prognostic value of baseline PSA in PROCEED, a phase IV registry study in mCRPC patients.

For PROCEED, mCRPC patients were scheduled to receive three sipuleucel-T infusions at ~2-weekly intervals. A key inclusion criterion was subjects with advanced prostate cancer who were set to receive sipuleucel-T or who underwent their first leukapheresis for the manufacturing of sipuleucel-T <6 months prior to enrollment. The primary objective was cerebrovascular event risk and the secondary outcomes were OS and time to death from disease progression, stratified by baseline PSA. Patient follow-up was every 3 months after sipuleucel-T for 3 years minimum or until death or withdrawal. 

There were 1,976 patients enrolled in PROCEED between 2011–2017, with a median age of 72 years, with the majority of patients were Caucasians (87%). The median baseline PSA was 15 (0–7497) ng/mL.  Just over half of the patients had a Gleason score ≥8 (51%); prior therapies included local (78%) and hormonal (99%). Overall, 1,255 patients died (63.5%). All outcomes were significantly worse in the 2nd, 3rd& 4th PSA quartiles vs the 1st (lowest PSA) quartile. 


Overall survival and time to first cerebrovascular event were longer in sipuleucel-T treated patients in the lowest baseline PSA quartile vs sipuleucel-T treated patients with higher PSA. Survival of nearly 5 years was seen in the lowest PSA quartile. Although PROCEED did not have a comparator arm, the trend for longer OS is concordant with that seen in IMPACT, and PROCEED externally validates the cohort from the post-hoc analysis of IMPACT. Clinical trial information: NCT01306890 


1. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010;363(5):411-422.
2. Schellhammer PF, Chodak G, Whitmore JB, et al. Lower baseline prostate-specific antigen is associated with a great overall survival benefit from sipuleucel-T in the Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial. Urology 2013;81(6):1297-1302.

Presented by: A. Oliver Sartor, MD, Tulane Medical School, New Orleans, LA

Co-Authors: Celestia S. Higano, Matthew R. Cooperberg, Nicholas J. Vogelzang, Shaker R. Dakhil, Christopher Michael Pieczonka, Jeff Vacirca, Raoul S Concepcion, Ronald F Tutrone, Luke T. Nordquist, Carl A Olsson, David F. Penson, Ian Schnadig, James L. Bailen, Bryan Mehlhaff, Nancy N. Chang, Nadeem Anwar Sheikh, Bruce Brown, Andrew J. Armstrong; University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA; University of California, San Francisco, San Francisco, CA; Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Wichita NCORP, Wichita, KS; Associated Medical Professionals of New York, PLLC, Syracuse, NY; New York Cancer and Blood Specialists, New York, NY; Urology Associates P.C, Nashville, TN; Chesapeake Urology, Towson, MD; Urology Cancer Center and GU Research Network, Omaha, NE; Integrated Medical Professionals, PLLC, Columbia University Medical Center, North Hills, NY; Vanderbilt University Medical Center, Nashville, TN; Compass Oncology, US Oncology Research, Tualatin, OR; First Urology Research, Louisville, KY; Oregon Urology Institute, Springfield, OR; Dendreon Pharmaceuticals LLC, Seattle, WA; Dendreon Pharmaceuticals, LLC, Seattle, WA; Dendreon Pharmaceuticals LLC, Seattle, WA, US; Duke Cancer Institute, Duke University, Durham, NC

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA