In this large prospective analysis, African American race emerged as an independent predictor of longer OS in multivariate analyses, confirming observations of prior retrospective analysis of phase 3 trial data.
Sipuleucel-T (sip-T) is an FDA-approved autologous cellular immunotherapy targeting prostatic acid phosphatase among select men with metastatic castration-resistant prostate cancer (mCRPC). Previous retrospective analyses of three sip-T phase 3 trials showed a 30.7-month overall survival (OS) advantage for African American (AA) patients (pts) vs control pts while in the IMPACT trial, sip-T extended median OS by 4.1 mo vs control (McLeod AUA 2012 #P953). The PROCEED registry provides a prospective opportunity to confirm these observations in a larger group of AA pts.
Dr. Oliver Sartor, from Tulane University, spoke to UroToday about the implications of this provocative finding.
Q: What is the background against which the PROCEED trial data generated so much excitement for the care and outcomes of African American men with prostate cancer?
We’ve become accustomed to African Americans men with prostate cancer doing worse than Caucasians. Whether historically or currently, we end up with the same message: African Americans have more aggressive cancers; they are diagnosed at earlier ages; they are more likely to die from prostate cancer.
This finding was so exciting because it appeared that sipuleucel-T was more effective in the African American population, rather than less. Here is actually a therapy that not only helps people live longer, it helps African American men live longer than Caucasian men. That’s a very optimistic message.
Q: Was there something known about this agent that suggested or predicted that it would perform well or differently among African Americans versus a Caucasian or another population group?
In the cancer world, there is nothing that I am aware of. In this case [this study] we have an immunotherapy with more activity in African Americans than in Caucasians in any form of cancer that I am aware of. This may be a first.
This hint about this agent came some years ago from Dave McCloud, in a tiny study in which there was provocative suggestion -- a hint -- that African Americans may do better. Otherwise, within the rest of the literature, African Americans do worse.
The issue of more robust immune responses actually comes from vaccination literature, showing that with the same vaccine, the response might be more robust among African Americans.
So, I was anxious to look at this population across a broader number [of subjects].
We had 220 African Americans and 420 Caucasians – a pretty good sample set, all receiving the same treatment—[undergoing] multivariate analysis.
The bottom line is that the data held up.
This may be the first case of a treatment showing more activity in African Americans [than Caucasians] in a cancer population.Q: Could you describe PROCEED registry—its origins and purpose?
The PROCEED registry was mandated by the FDA to look at safety concerns and issues surrounding Provenge in a cancer population. Over 1,900 patients were accrued from a large number of sites and tracked: what therapies they received, when they died...
Patients’ previous treatments varied, and subsequent treatment varied, but everybody [in the Registry] received sipuleucel-T. The fact that the basic information from the Registry was intact enabled us to perform this comparison.
Q: Did factors other than race differ?
As expected, age was a prognostic factor, and as expected, alkaline phosphatase, which has been well demonstrated to be a prognostic marker in prostate cancer [was different]; [and] hemoglobin. A variety of markers in addition to race were predictive of survival. But those are things we already know about.
Q: Could you speak briefly to the study design and some findings?
The study design was as simple. People were selected by their physician to receive Provenge, and followed for survival. Everybody in the study received Provenge, and over time there were a series of deaths. Those were the two commonalities.
This was a registry rather than a clinical trial. [Enrolled patients] could have had a variety of prior treatments or post-treatments. All patients had castrate-resistant metastatic prostate cancer and all were chosen by their physicians to receive Provenge.
First, we did a matched population by PSA. The ages were the same. The ECOG performance statuses were a little worse in the African American population—34 vs. 25% for ECOG 1. PSAs were the same, but hemoglobin was a little lower in the African American population. People with low hemoglobin do worse, as we and many others have shown.
High alkaline phosphatase was worse, but the two populations were the same. LDH [values] were the same [between groups]. We were not able to put this in the multivariate analysis as we didn’t have enough samples to be definitive. It is generally better to have prior local therapy, yet African Americans were worse…
[Persons] who have had prior chemotherapy usually have a worse prognosis. In this case, the African Americans did a little better.
At baseline there were some differences. African Americans were less likely to have had surgery; and more likely to have a worse performance status. They were more likely to have a low hemoglobin.
Our multivariate analysis took these factors into account, When we looked at everything in the Provenge-treated population, all [factors] were predictable except for race. African Americans still had a worse prognosis.