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Dan George: Hi. I'm Dr. Dan George. I'm a Professor of Medicine and Surgery at Duke University Medical Center and Director of GU Oncology and Co-Chair of the Duke DCI Center for Prostate and Urologic Cancers. And I'm here today with my colleague, Dr. Megan McNamara, also a medical oncologist at our Duke Cancer Institute, and we're talking about a study that we recently presented at the Genitourinary Cancer Symposium on the VA database and the outcome of patients treated with abiraterone or enzalutamide according to race.

Megan, tell us a little bit about the study.

Megan McNamara: Yeah, so this is an interesting study that we did looking at patients with metastatic castrate-resistant prostate cancer who had not received chemotherapy for mCRPC and were treated with abiraterone or enzalutamide, specifically VA patients. And what we found was that patients who were African American had longer survival when they were treated with abiraterone or enzalutamide compared to white patients. 

Dan George: So this is a little bit surprising. I mean, Megan, we think about patients with African ancestry, African American patients, as having a disease that's more aggressive, a disease that's presenting at a later stage, perhaps becoming metastatic sooner, and even having a much higher rate of death from prostate cancer. So help me understand a little bit ... This seems like a paradox. What's going on?

Megan McNamara: Yeah. Exactly. So we know that African Americans have 2.5 times higher risk of mortality from prostate cancer compared to Caucasians, and yet, we're seeing this emerging kind of growing findings in our field with several different therapies, docetaxel, Provenge, abiraterone, and our studies really build on that, that even despite the fact that they have more, African Americans have more aggressive prostate cancer, they have higher mortality for prostate cancer, there is a paradox, exactly like you said, that they appear to respond better to prostate cancer treatments, and that's what our study shows, as well.

Dan George: You know, it's really interesting. So we can see that sometimes at the tumor level, right? PDL1 status, associated with worse outcome in cancers, but more responsiveness to PDL1 inhibitors.

Megan McNamara: Yep.

Dan George: So it looks like now we're looking at the, you know, at the host level, the germline level, with these patients, associated with race, something's going on that's affecting these cancers that's making them more responsive, not just to hormonal therapy, you're saying, but to chemotherapy and immunotherapy, as well.

Megan McNamara: That's right. That's right.

Dan George: You know, it's interesting. You brought up these other studies with docetaxel and with sipuleucel-T, and those are really based on clinical trial data. Susan Halabi did a nice presentation, just published in JCO, a meta-analysis of 11 different Phase 3 clinical trials with small percentages of African Americans in each. The sipuleucel-T was a prospective registry that patients consented to and accrued to. Your study's different. How is it different?

Megan McNamara: So the key difference with our study is that these are real world patients. So these are patients that are not kind of a selected trial population. These are real world patients who are just getting treatment in the VA that we captured in our database and in our study. And that's really the key difference because they're kind of more relevant to patients who are just in the clinic.

Dan George: Yeah. This really, it's real, kind of, you know, mimicking our own practice experiences. In fact, I think, you know, you show some of the data around their comorbidities. You know, we see high rates of pretty significant comorbidities.

Megan McNamara: Yep.

Dan George: And in this patient population, even higher in some of the African American cohort than in the white cohort. And yet, you know, we're still seeing this prolongs overall survival. Not just cancer-specific survival.

Megan McNamara: That's right. Yeah. We saw more hypertension and diabetes in the African Americans, which you might think would be reasons that they would have shorter survival, but even despite that, we still observed that they were living longer when treated with abiraterone and enzalutamide.

Dan George: You know, the VA's an interesting system because ... For a lot of reasons. But one of them is because this is really kind of like a, you know, a full coverage system for these patients, so there's not the sort of financial burden of the medicine, and these patients that are part of the VA system, they have equal access to these drugs. I mean, what does this say about the health disparity we see with race and treatments?

Megan McNamara: So that's a really key aspect of our study, the fact that we used the VA database helps control for access to care, which can be one thing that sometimes might cause reasons for differences between survival. So we potentially eliminated that or reduced that by controlling for access to care, so that really lets us hone in on the biological differences that are contributing to survival, which is really what we want to identify and understand. 

Dan George: All right, great. So where do we go from here?

Megan McNamara: That's a great question. So you know, I think the next step is really two key things. So this was a retrospective study. It was a large sample size, but it was still retrospective, which is potentially vulnerable to the limitations of retrospective studies. So the next step is to do a prospective study that validates these findings prospectively and will also allow us to collect samples so that we can do correlative analyses to try to understand what is the difference, why is there this difference in survival.

And then I think the next step is also to try to move this earlier. So these are pretty advanced patients, metastatic castrate-resistant patients. What would happen if we moved this earlier into hormone-sensitive disease or even high-risk localized disease? Would the benefit be even greater? 

Dan George:: That's really exciting, you know, and when you think about it, this patient population being even benefiting to a greater extent ... Perhaps we're really underestimating the effects of these drugs because these patients aren't really part of our clinical trials. They're underrepresented in our clinical trials.

Megan McNamara: Yep.

Dan George: Imagine if a third of our patients in castrate-resistant prostate cancer trials were African American? We might even see a greater overall response in survival associated with these agents.

Megan McNamara: Yeah. Completely agree. Yep.

Dan George: Well, great. Well, great work. Thanks for sharing.

Megan McNamara: Thank you. Thanks for having me.