Biomarker-Directed Therapy in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) - Clara Hwang
October 16, 2022
Clara Hwang, MD, Medical Oncologist, Henry Ford Cancer Institute, Detroit, MI
Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts
Alicia Morgans: Hi, I'm so excited to be at ASCO 2022 where we had the opportunity to see some excellent data presented during the ASCO Poster Discussion session, some of the work done by Dr. Clara Hwang. Thanks so much for being here.
Clara Hwang: Oh, thanks for having me. I'm really excited to talk about our work. Absolutely.
Alicia Morgans: Wonderful. Well, can you tell us a little bit about it? Set the stage for us, let us know what you studied, what you investigated, and what you found.
Clara Hwang: Sure. So we were really motivated by the known disparities in Black versus white men. So we know that Black men are about twice as likely, actually more than twice as likely, to die from prostate cancer than white men. And so that motivated our work. And what we did was we wanted to explore this in the setting of precision medicine for prostate cancer. So now this has become the standard of care. So we know that there are certain biomarkers for which we can prescribe targeted therapies. And so we wanted to ask a couple of questions. So number one, were there are differences in the frequency of these alterations for Black and white men? And then number two, were there differences in treatment patterns for these molecularly defined cohorts?
Alicia Morgans: And I think one of the more powerful things about this study is that you were able to do this within the PROMISE Consortium. Can you tell me a little bit about that group that's worked together to gather data?
Clara Hwang: Yes, the PROMISE Consortium, it's a collaboration between about 18 different institutions. And the goal of this consortium is to collect clinical, so very high-quality clinical data along with genomic data. So all of the men in this database have had either somatic or germline genetic testing.
Alicia Morgans: And I think that's so important because it gives you the opportunity to have enough of a sample size of a racially diverse group, which would be so hard in a single institution.
Clara Hwang: Yes, that's so true. In the end, our sample size for this particular analysis was about 1,000 patients.
Alicia Morgans: That's huge. Fantastic. And what did you find?
Clara Hwang: It was about 20% African American and then 80% white. So we looked just at Black versus white men. And so we looked overall at actionable alterations and we defined that as mismatch repair deficiency or homologous recombination repair deficiency or high tumor mutational burden. And so overall we didn't see any differences in the Black versus the white cohort. But when we looked down to the cohort of patients who had mismatch repair deficiency or MSI high, we did find that that was more frequent in our Black patients than the white cohort. Yes, it was about 9% versus about 4%.
Alicia Morgans: That's really interesting and so important again that you had such a large sample size that suggests that this may be a real difference, at least among the patients who are enrolled in this particular registry. What do you do with that information?
Clara Hwang: Well, I think, first of all, we need to make sure we're looking. As you mentioned this, these patients in the registry, they had all had genetic testing. So we weren't really able to ask the question, are all men getting genetic testing? So I think that's, first of all, a very important question. But then the next question really is, how do we treat these men and what are their outcomes with, for example, targeted therapies? So we also looked at whether men who had actionable alterations, whether they did receive targeted therapies. The individual cohorts were kind of small. So although we saw differences, they weren't statistically significant. But when we looked at the combined cohort of all men who had an alteration that could be prescribed targeted therapy, we did see differences in the frequency with which targeted therapy was prescribed.
Alicia Morgans: And what were those differences?
Clara Hwang: We did find actually that Black men were less likely to be prescribed targeted therapy than white men. So I think this is actually where our responsibility comes in as an oncology community, right? The biologic difference, we don't really have a whole lot of control over that, but we do have the ability to prescribe these targeted therapies to our patients, make sure they have equal access to these therapies. So I think that's really where our responsibility lies.
Alicia Morgans: And there could be so many reasons. Maybe it's because of disease biology and clinical presentation.
Clara Hwang: Absolutely.
Alicia Morgans: But at the end of the day, a difference is a difference. And it is, as you said, our responsibility to try to get these patients the treatments that we know can benefit them. And so important to measure differences, identify them so that we have that feedback reflected and we can say, we're doing something differently for these populations of patients. How do we make it better?
Clara Hwang: Yes, absolutely. And you're right, we don't understand exactly why we see these differences in treatment patterns. They could be start some of it institutional, some of it could be maybe the Black men that we studied were earlier in their treatment course, so it wasn't appropriate yet maybe to offer them targeted therapies. Some of it could be availability of clinical trials too, because some of the patients who received targeted therapy did have it prescribed as part of a clinical trial. So yes, we don't understand all of those differences, so we're hoping to look at that in the future.
Alicia Morgans: And so important. Well, I'd love to hear what message you have to the audience, just sort of a closing thought or summary for this very important study that is one of the first to really shine a light on differences between Black and white men who are treated at least in the US and who were identified through this PROMISE Registry.
Clara Hwang: I think the take-home message is, number one, we do have to look for these alterations. So it's very important to do this biomarker testing. And then I think the next message is, is that we need to make sure we're using this information and prescribing target therapy to people who qualify.
Alicia Morgans: And it's important for us to consider that we have to treat the patient, whoever he is, and make sure that he gets the right therapy for him and not use anything other than the disease characteristics, the patient's preferences, and the right treatment for that individual, certainly not race as we're making those decisions.
Clara Hwang: Absolutely.
Alicia Morgans: And I sincerely appreciate your help.
Clara Hwang: Thank you very much.