Prospective, Real-World Data Analysis Showed Additional Overall Survival Benefit with Sipuleucel-T in African American Patients – Oliver Sartor

Oliver Sartor joins Charles Ryan in a discussion on a Phase 4 registry trial in men with metastatic castration-resistant prostate cancer (mCRPC).  The IMPACT study analyses suggested that overall survival (OS) was longer in treated and control patients with low baseline PSA, and OS benefit was greatest for sipuleucel-T versus control in the patients with the lowest PSA (Schellhammer Urol 2013). Eligible mCRPC patients were scheduled to receive 3 sip-T infusions at ~2-weekly intervals. Dr. Sartor explains that the objectives included cerebrovascular event risk (primary) and OS (secondary). Follow-up was every 3 months after sipuleucel-T for 3 years minimum or until death or withdrawal. This analysis provides data on 221 African American (AA) patients and 1649 Caucasian (CAU) patients who received sipuleucel-T. In terms of all patients, the median overall survival (OS) for AA patients was 35.2 months and the median OS for CAU patients was 25.8 months. When patients were matched for prostate-specific antigen (PSA), prognostic variable for overall survival after treatment with sip T, AAs continued to maintain an overall survival advantage with a median OS of 35.3 months compared to 25.8 months for CAU patients. The median baseline PSA prior to sip T was 29.48 ng/mL. Among patients with PSAs less than 29, the median OS was 54.3 months in the African American cohort and 33.4 months in the caucasian cohort. After adjusting for other known prognostic factors, AA race was associated with prolonged OS benefit compared with CAU, HR=0.60, 95% CI 0.48–0.74; p < 0.001.  

AA patients from the PROCEED registry have improved overall survival compared with CAU patients after treatment with Sipuleucel-T. This difference is most pronounced for patients with a low PSA prior therapy – a difference of 21 months. Additional prospective correlative studies are necessary to examine why this difference exists – and if such a difference may exist for other immunotherapies.

Biographies:

A. Oliver Sartor, MD, Professor of Medicine and Medical Director, Tulane Cancer Center; C. E. and Bernadine Laborde Professor of Cancer Research, New Orleans, Louisiana, United States

Charles J. Ryan, MD, The B.J. Kennedy Chair in Clinical Medical Oncology at the University of Minnesota and Director of the Division of Hematology, Oncology and Transplantation, Minneapolis, Minnesota, United States
Read the Full Video Transcript

Charles Ryan: Hello. Today we're talking from ASCO 2019 in Chicago and I'm delighted to be joined by Dr. Oliver Sartor from Tulane University. Oliver, always a pleasure to speak with you a lot going on as usual. I wanted to start with a couple of things you're involved in or particularly knowledgeable about. First is the PROCEED data issue around race and outcomes on sipuleucel. Very interesting. Tell us about that work.

Oliver Sartor: Yeah, so first of all, thanks for having me, Chuck, and we've been involved with sipuleucel-T and PROCEED registry for a long time and, when we set it up initially we weren't exactly sure what we were going to do. It's set up under an FDA mandate actually to a potential cardiovascular and stroke events. Turns out there's nothing there and I didn't ever think there was anything there. We have the opportunity to collect prospective data on about 1,700 patients, treated in real-world settings. So this is just people going in to get their SIP-T as they would in commercial product. And that's exactly what we did and then we followed.

And the most interesting thing out of the registry in my opinion was the fact that we had a fair number of African Americans. We had about 220 African Americans, and the majority were Caucasian, but then a few other ethnic groups. Not enough to analyze any other ethnic groups. But we did a direct comparison between the African American outcomes for survival because of course, we can ascertain survival very cleanly. And the Caucasians and when we did the overall sort of analysis, it turns out that African Americans were living longer. Now you may or may not be aware, there've been a series of studies, Susan Halabi has done some. And then there's a little trial with abiraterone called Abi Race trial that Dan George presented on last year, also sort of suggesting African Americans would do better. But those differences were relatively minor. These differences were relatively large.

We then had a lot of background heterogeneity in terms of PSAs and African American PSAs were higher. And so we ended up doing a matched-pair analysis and we just took the PSAs, that's known to be important for sipuleucel-T, and we did two-to-one matching, and then we really crunched the numbers and every sort of analysis you can imagine. Bottom line is very, very, very substantial improvement about eight to nine month improvement for the sipuleucel-T overall. We looked at the lower PSA as you may or may not be aware that-

Charles Ryan: I'm going to stop you there. Just so the viewers know. an eight or nine month improvement in survival for the African Americans-

Oliver Sartor: ... For the African Americans.

Charles Ryan: ... relative to the non-African Americans-

Oliver Sartor: Relative to the Caucasians. Yeah.

Charles Ryan: ... Caucasians I presume was the majority of remainder.

Oliver Sartor: Yeah. And so, a very substantial advantage. Much different than kind of one or two month type of things. This is now what's previously reported. And then you may or may not know there was a Paul Schellhammer paper with sipuleucel-T, suggesting the benefit was magnified for those with a lower PSA. So we did that type of analysis as well. And it just absolutely got huge.

Charles Ryan: Right. Quartiles of disease, the lowest quartile of disease. And I've actually always used that as a guide for therapy. My use of sipuleucel-T has been in the patients who have longer, sorry, lower PSAs and better prognoses and longer survivals already. So it's always sort of made me wonder about a selection bias issue, but you saw that quartile effect?

Oliver Sartor: Absolutely. So we analyzed by quartile. We had African-Americans, we had Caucasians, everything matched out and it was a huge benefit in the African Americans. And then, we have to ask why? Is there something about the tumors? Is there something about the immune response? And of course we don't know, unfortunately, don't really have correlations. We don't really have biologic specimens. This is run in a real-world setting. But I'll say that it was substantial. Very substantial.

Charles Ryan: Okay, interesting. It's really interesting to see what's happening with regards to race. We've known for a long time that African Americans have a higher risk of dying from this disease but, we're beginning to see pockets of the disease and perhaps particular therapies that have some benefit even in this more aggressive disease phenomenon. We're also seeing, I think you'd agree, that if we correct for other factors that African Americans in some instances don't have a worse prognosis. And so it's engaging us in a debate around biology versus patterns of care and those types of things.

Oliver Sartor: Absolutely, couldn't agree more Chuck. And you know, the patterns of care ... very, very interesting questions in that arena. And of course, there's a lot of disparities with regard to access to care. And that's one of the reasons we did the PSA matching in this particular analysis because people were coming in, African Americans were coming in later with worse disease. They still did better. And so, it was really sort of surprising.

Anyway, the next step there is to really delve into the biology more and to really begin to understand there is some data from the non-cancer literature that the immune response as in African Americans to vaccines may actually be enhanced relative to Caucasians. So it could be that there actually is an immune sort of recognition phenomenon. That's just saying that we have to do so much more work before I could ever state that in cancer.

Charles Ryan: So, what's the take-home message for the treating clinician, urologists or oncologists now hearing this from you? What do they say to their patients about it?

Oliver Sartor: Well, first of all, I think if you are caring for African American patients, you really ought to consider the sipuleucel-T as an option, because the outcomes were better than expected. And second of all, I think these data underscore the fact that probably the most benefit is in the group of patients who have a relatively low PSA, kind of low volume to begin with. You don't want to be treated with some sipuleucel-T when the PSA is 500 and rising rapidly. That's not the subset.

Charles Ryan: I wanted to ask you a question on this data about response to therapy. We talk about survival as the primary outcome of the sip-T studies, and it has been. But the response to therapy been really low. Do we see an increase in the response to therapy with the African Americans?

Oliver Sartor: No. We really couldn't tease at that. We weren't really well-designed in this registry-type setting. One of the other things we captured nicely was actually additional therapies that were administered. And, one of the things that could potentially have explained better outcomes from African Americans is maybe they got more therapy, more intensive therapy, better therapy after the sipuleucel-T was administered. That, of course, was not the case. There were no real differences.

Charles Ryan: Right. Okay, great.

Oliver Sartor: Yeah.

Charles Ryan: Great.
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