Read the full video transcript:

Dr. Alicia Morgans: Hi, and welcome to ASCO 2018 coverage. Chuck and I are delighted to have with us Dr. Susan Halabi, who is a Professor of Biostatistics and Bioinformatics at Duke, and who is the first Biostatistician to become a fellow of ASCO, so thank you so much for being here with us today, Susan. 

Dr. Charles Ryan: And congratulations. 

Dr. Susan Halabi: Thank you Dr. Morgans and Dr. Ryan. I'm delighted to be with you this afternoon. 

Dr. Alicia Morgans: We're really excited about a presentation that you're going to be giving here at ASCO. Can you tell us a little bit about that?

Dr. Susan Halabi: I'm delighted to give you an overview of my presentation. We know that African-American men are diagnosed at a later stage of diagnosis in the United States. We also know that African-American men have higher incidence and mortality rates than Caucasian men. We also know that African-American men have unequal access to health care. 

Now, all this information is based on the US population, so we wrote a proposal that was funded by the Department of Defense to answer a specific hypothesis, and that is:  Are African-American men more likely to have shorter survival, and worse survival outcomes than Caucasian men?

In order to test this hypothesis, we pulled data from nine clinical trials that included about 9,000 men. These are all men with metastatic castrate-resistant prostate cancer, that were enrolled in phase-three trials that randomized patients to either docetaxel prednisone, or docetaxel prednisone Plus, an experimental arm. 

What's really interesting is in all of these trials there was no survival advantage, so from a statistical point of view it was very easy to perform this kind of analysis. 

Now, remember our original hypothesis was that African-American men did worse than Caucasian. When we looked at a univariate analysis we were comparing the survival distribution in African-American men versus Caucasian. 

To our surprise, African-American men had a very similar survival distribution compared to the Caucasian men. They both had about a medium survival time of 21 months, but when you look at the nitty details and do more ... you zoom in and you do analysis adjusting for any imbalances that may affect the survival outcome, what we found out was the hazard ratio was .81 for African-American men, compared to Caucasian men, which is ... really this is a very striking finding, and it is important to know that only 500 of the over 8,000 men were African-American men, so I think the key take-home messages, I would say are the following:

The first one is that we observed, in general: low enrollment of African-American men in all these trials. Now, only three of the nine trials were conducted in the US, and they were conducted by the NCI, National Cancer Clinical Trials Network. 

From these three trials, when we zoom on those three trials and we perform the same analysis, the results are even more striking. In fact, African-American men had better survival median of 21 months, compared to 20 months in about 30% of the patients that were enrolled by the NCI NCTN, and the hazard ratio was .76, and this was highly significant. 

But, what's important to know, is this is really not a criticism about industry trials, because, as we all know, industry trials are conducted globally, and it's going to be very difficult to enroll African-American let's say from Europe, and from Asia; but I think the take-home message here is we all as scientists, researchers, and medical oncologists, we really need to make concerted efforts to vigorously enroll African-American men so they are well-represented in clinical trials.  And, when you eliminate access to clinical trials, actually African-American men are doing better than white men.

Dr. Charles Ryan: Does this mean we should be stratifying by race in trials, in order to balance if we have one group that's going to do better than another group? Should that be a stratification factor? 

Dr. Susan Halabi: Dr. Ryan, this is an excellent question, and I don't think I yet have an answer to that question, because we're not sure why we have these results. Does that mean that African-American men have biologically different disease than Caucasian men? Or is it an issue of access to care, or is it that African-American men respond better to treatment?  I think these are unanswered questions, but I think this is the largest analysis to date that has been undertaken, and sadly enough, even though it's the largest analysis, only 500 men out of the 8,000 were African-American men.

Dr. Charles Ryan: Do you think this applies to docetaxel treatment, and abiraterone treatment? And any other therapies in there?

Dr. Susan Halabi: This is an excellent question. The phase-three trials were only based on docetaxel           prednisone, so you cannot generalize these results to the general population, because you have only patients who were treated with docetaxel, and also you cannot generalize these results, because as we know, only 3% of cancer patients in the US are enrolled in clinical trials; so because of those two factors, I would say maybe this ...This is why the results are unexpected. It may be that African-American men who enrolled in those trials were heavily selected to be the fittest.  Because all these patients were treated with chemotherapy. 

Dr. Charles Ryan: Right.

Dr. Alicia Morgans: That's true, but it really does speak to the fact that there could be differences that we're not measuring, whether these are driven by some constellation of genetic polymorphisms, which is probably what's happening if it's truly happening. 

And that, we should really strongly play a role in trying to enroll a diverse group of patients in our clinical trials, and maybe that could be balanced by stratification if we need to, but we should at least take the first step, as your group, I think, has done in the Abi Race Study, to look at all of our therapies in a more racially-diverse way. 

Dr. Susan Halabi: Yeah, I totally agree. I think this area is going to be a rich area for future research. Definitely, this has really opened our eyes to the fact that African-American men who have access to clinical trials, will do not even as well as white men, but even better. But, we really need to dissect this. Is it due to biology, or is it due to access to care? 

And the interesting finding here is that when you give African-American men access to clinical trials, we're eliminating the disparity, and I think this is a…

Dr. Charles Ryan: They do better. 

Dr. Susan Halabi: Yes, they do better, so this is a huge finding. 

Dr. Charles Ryan: Yeah, it's a paradox because we've been taught, and we expect that the outcomes are uniformly worse for African-Americans, and one of the reasons we need to enroll them in clinical trials is because they have such a greater need, and now we have a new finding. It's really the second potential paradox recently in prostate cancer. 

The first being this idea that patients who have these MSI-High tumors have a really good response to immunotherapies where we previously knew that these had a more aggressive disease. It's really kind of a fascinating series of findings in the world in prostate cancer right now. 

Dr. Susan Halabi: Right. 

Dr. Alicia Morgans: I don't think that we should rest, though, and say that these patients ... I think we still need to look for difference, because what Susan said that was really, really important is that we may be selecting a population of men who are destined to do better. 

Dr. Charles Ryan: Yeah. 

Dr. Alicia Morgans: Because they only had ... There's only a small group of these men who have access to clinical trials. It's such a small percentage of the overall population, and if we really want to answer this question, if we really want to personalize care for men of African-American descent, we need to actually engage them where they are, so going to the clinics where these men are receiving normal care, not just identifying those men who are fit enough to come to Duke, for example, and enroll in a clinical trial. We need to get all comers, and I think that's going to be a critical part of answering this question in the future. 

Dr. Charles Ryan: Of course, it could be that the African-Americans have a specific gene that is associated with a better response, that is not specific to that population, that many of us also have. 

Dr. Alicia Morgans: Yes. 

Dr. Susan Halabi: Right. 

Charles Ryan: It's just less ... It's less prevalent. 

Dr. Susan Halabi: Right. 

Dr. Charles Ryan: If we could find that molecular link, that would also be really important. 

Dr. Susan Halabi: Right, and this is really the next step that we're looking at. Out of the three clinical trials that's funded by the NCTN, we have access to GWAS data from a study conducted in our group, CALGB9401, and this is what I'm doing. I'm looking at genetic polymorphisms in African-American men and white men, but unfortunately, when you look at definition of African-American, and you look at genetically the sample size, unfortunately it does become really small, so we have some challenges in answering this question.

Nevertheless, I think this underscores the importance of enrolling men of African-American descent and other minorities, because I think all drugs that are going to be approved in the United States and Europe should take into account the population, so they are well represented in these trials. 

Dr. Charles Ryan: But also, African men in Africa have a very high and even increasing risk of prostate cancer over time, where cancer is now becoming the lead cause of the death in the African sub-continent. 

Abiraterone, for example, is going to be generic in the US, and so could become widely available in Africa soon, so this is a finding that says, “We have now a therapy that is potentially,” and that would obviously require some validation, but, “potentially even more useful in an area of greater need such as Africa, in a situation where there's highly prevalent and more aggressive disease”. 

Dr. Susan Halabi: I totally agree that, and I think that there should be some measures from all groups, whether the funders, whether it's advocate groups. I think there should be more awareness, more training maybe of African-American men to the doctors, build trust in these communities so people feel that at the end of the day we're all benefiting from enrollment in these clinical trials. 

Dr. Alicia Morgans: And particularly them, because if these differences exist, we want these benefits to exist for everybody, not just the men who enroll in these clinical trials. We want everyone to be able to benefit, and we want to understand that benefit on a much deeper level, so I commend you for this. 

Dr. Susan Halabi: Thank you. 

Dr. Alicia Morgans: Do you have any closing thoughts as we wrap things up? 

Dr. Susan Halabi: Right. I would like to mention, because I talked a little bit about the trials, and three out of the nine trials were done by the NCTN, and what's interesting is that we found a huge difference in terms of enrollment between NCTN groups and the industry trials. 

For instance, 12% of all enrollment in NCTN were African-American, versus only 4% in industry, so if the NCTN, with limited resources, are able to enroll African-American men, why are we not doing it? We should be doing this. Everyone should benefit from these drugs, and from these clinical trials, and we need to ...It's really badly needed to collect specimens and do more in-depth molecular and genetic analyses. 

Dr. Alicia Morgans: Absolutely. It's time to really personalize not just to the molecular change that's driving things, but really the entire spectrum of differences in our patients, so that we can really understand what we expect in terms of outcomes, and what we ... what we can hope for, so thank you, again, for your work. 

Dr. Susan Halabi: Thank you. It's my pleasure.