Findings Highlight Efficacy of Sipuleucel-T in African-American Men With Prostate Cancer

Oliver Sartor, MD

The median overall survival (OS) for African-American patients who received sipuleucel-T (Provenge) as a treatment for metastatic castrate-resistant prostate cancer (CRPC) increased by nearly a year when compared with Caucasian patients, based on preliminary data from the PROCEED registry presented at the 2017 American Urological Association.

“The basic ‘punchline’ for this study is African-Americans see more of a benefit with sipuleucel-T based on the PROCEED registry report,” said Oliver Sartor, MD.

PROCEED enrolled 420 Caucasian patients who were matched with 210 African-American patients by baseline prostate-specific antigen (PSA). OS was examined with univariate and multivariate analyses evaluating independent factors.

OS was 39.5 months for African-American men compared with 28.1 months for Caucasian patients. African-American race emerged from this research as an independent predictor of longer OS, but further biological studies need to be done to determine the reasoning behind these results.

OncLive: Can you give an overview of this study?

What were the most significant findings?

In an interview with OncLive, Sartor, a medical oncologist at the Tulane University School of Medicine, discussed the analysis of African-American men receiving sipuleucel-T for CRPC compared with Caucasians, and the implications of this research.Sartor: I think most individuals are familiar with sipuleucel-T as it's been FDA approved since 2010. As part of that initial approval, the FDA requested more analyses. The response was to put together a registry called PROCEED. There are more than 1900 patients in the registry and this was a real-world experience where individuals who are receiving sipuleucel-T commercially have their various demographics and basic biochemical levels put into a database. They are followed for survival along with additional therapies. It's a simple concept of people treated with sipuleucel-T. The analysis was focused on African-Americans as compared to Caucasians. Unlike many studies in the past, there was a very positive effect for African-American patients. In fact, it was surprisingly large. The basic punchline for this study is: African-Americans see more of a benefit with sipuleucel-T based on the PROCEED registry report.

Can you explain the science behind these results?

The way we did the analysis was relatively convincing. We know PSA is important when it comes to predicting sipuleucel-T responsiveness and survival. We matched 420 Caucasians with 210 African-Americans looking at all their PSA scores. We then looked at a multivariate analysis to make sure that African-Americans would continue to have the effect when other factors, such as hemoglobin and alkaline phosphate were taken into account. The bottom line is we had a multivariate analysis, which in my opinion is quite convincing.There are 2 basic theses that you could propose. The first is that the immune system is reacting more appropriately in African-Americans—meaning the immune system in African-Americans is more effective at slowing cancer growth.

The other hypothesis is the tumors present in African-Americans might be more prone to being attacked by the immune system. Of course, you can also combine the 2 hypotheses. It could be better immune systems and more responsive tumors, but none of this has been tested yet.

What are the major implications of this analysis?

In my opinion, the concept of a more active immune system in African-Americans has some credence, but of course, that's more of a hypothesis than a fact. There are several major implications. The first is, African-Americans with metastatic CRPC who are candidates for sipuleucel-T, should all have access to sipuleucel-T.

Secondly, I am going to make sure they get it early when the PSA is relatively low because that is when the best outcomes were seen. From my prospective, African-Americans ought to get sipuleucel-T because it appears as though their responsiveness was quite high.

What is the safety profile different with sipuleucel-T?

What are next steps with this research?

There are also more implications, but this could also lead to a broader hypothesis that perhaps African-Americans are more responsive to immunotherapy across a wide spectrum of cancers. If that's true that's a huge implication, but of course, that is just a hypothesis; we have to prove it and determine if it’s true or not.Sipuleucel-T is a very safe product. You can have a few headaches, chills, and flu-like symptoms. There is not really any difference that is apparent in the toxicity, but the toxicity is moderate anyway. One question that we need to settle is to now look at the cellular immunity and the actual changes in the cells in the sipuleucel-T─treated patients, both Caucasian and African-American. We need to explore more cellular studies to look at this immune response.

What are the main points that you would like the audience to take with them?

The second is, as I raised the hypothesis earlier, we need to determine if the immune therapies are more active in ethnic groups, particularly African-Americans, going forward because now immunotherapy affects many different tumors, making this question very important. The first point is that African-Americans receiving sipuleucel-T do better than expected and in this comparative analysis, African-Americans do better than Caucasians, particularly with low PSAs—25 or lower.

Are there any combinations with sipuleucel-T currently under investigation?

Take home point number 2 is we need to learn a lot more. There are some hypothesized studies of sipuleucel-T in combination but at this point it's too early to speculate.

Sartor AO, Armstrong A, Ahaghotu C, et al. Overall survival analysis of African-American and Caucasian patients receiving sipuleucel-T: preliminary data from the PROCEED registry. J Urol. doi:10.1016/j.juro.2017.02.1089.