Provenge and Clinical Outcomes by Baseline PSA Level

The following information was presented at ASCO 2018 by A. Oliver Sartor, MD, Tulane Medical School, New Orleans, LA.

Provenge (Sipuleucel-T) is the first and only FDA approved immunotherapy for men with prostate cancer. It was approved for men who have metastatic castration-resistant prostate cancer (mCRPC) and who are also asymptomatic or minimally symptomatic.  

Provenge was approved because of the results of the phase III clinical trial named the IMPACT trial. It randomized 512 men with mCRPC in a 2:1 ratio to receive Provenge (n=341) or placebo (n=171). The trial’s primary endpoint was overall survival (OS), adjusted for baseline levels of serum PSA and lactate dehydrogenase. 

The trial demonstrated that in the Provenge group, there was a relative reduction of 22% in the risk of death as compared with the placebo group corresponding to a 4.1month improvement in median survival (25.8 months vs. 21.7 months). 

As required by the FDA, there was a post-hoc analysis of the men participating in IMPACT assessing the prognostic and predictive value of baseline variables.

The analysis showed that the PSA was the strongest baseline predictor of overall survival (OS) with the greater benefits being experienced by men with lower PSA values.  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.

Since Provenge was the first cancer vaccine, the FDA required that there be a second, confirming study prior to their approving the treatment.  This trial, PROCEED, also evaluated men with mCRPC.   The primary objective of PROCEED was to evaluate the cerebrovascular event risk and the secondary outcomes that were evaluated were OS and time to death from disease progression, stratified by baseline PSA. Men from this trial were followed every 3 months after Provenge for 3 years minimum or until death or withdrawal. 

The PROCEED trial included 1,976 subject men.   Their median baseline PSA was 15 (0–7497) ng/mL.  Just over half of the men had a Gleason score ≥8 (51%); prior therapies included local (78%) and hormonal (99%). Overall, 1,255 of the men died (63.5%). Like in IMPACT all the outcomes were significantly worse in the 2nd, 3rd& 4th PSA quartiles vs the 1st (lowest PSA) quartile. 

Additionally, the overall survival and time to first cerebrovascular event were longer in the men who received Provenge and who were in the lowest baseline PSA quartile vs those who had 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 consistant with that seen in IMPACT.  PROCEED clearly validates the cohort from the post-hoc analysis of IMPACT. 


We have always recommended that Provenge be used early in the disease.  Unlike our other treatments for metastatic prostate cancer, Provenge takes time to become effective.  Lower PSA means that, in most incidents, it is earlier in the disease process.  Given our long time held belief and this new evidence, Cancer ABCs strongly recommends that the day you find out that you have become castrate resistant is the day you should begin to arrange for getting Provenge.  Why wouldn't you?  

Clinical trial information: NCT01306890 


1. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med2010;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. Urology2013;81(6):1297-1302.

Joel T. Nowak, MA, MSW wrote this Post.  Joel is the CEO/Executive Director of Cancer ABCs.  He is a Cancer Thriver diagnosed with five primary cancers - Thyroid, Metastatic Prostate, Renal, Melanoma, and the rare cancer Appendiceal cancer.