Metastatic Hormone-Sensitive Prostate Cancer: Data From ARASENS and ARANOTE

EP: 1.Breakthroughs in Imaging Modalities for Prostate Cancer

EP: 2.Prostate Cancer Imaging: Unmet Needs and Knowledge Gaps

EP: 3.Recent Progress in the Prostate Cancer Treatment Landscape

EP: 4.Key Unmet Needs in Prostate Cancer Management

EP: 5.Goals of Treatment for Non-metastatic Castration-Resistant Prostate Cancer

EP: 6.nmCRPC: Clinical Trial Data on AR Inhibitors

EP: 7.AR Inhibitors in nmCRPC: Real-World Data

EP: 8.Importance of Quality of Life When Choosing Therapy for nmCRPC

EP: 9.Non-metastatic Castration-Resistant Prostate Cancer: Patient Monitoring Strategies

EP: 10.Optimizing Care for Patients With Non-metastatic CRPC

EP: 11.Treatment Goals for Patients With Metastatic Hormone-Sensitive Prostate Cancer

EP: 12.Factors in Selecting Therapy for Patients With Metastatic Hormone-Sensitive Prostate Cancer

EP: 13.mHSPC: Use of Triplet Therapy

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EP: 14.Metastatic Hormone-Sensitive Prostate Cancer: Data From ARASENS and ARANOTE

EP: 15.Metastatic Hormone-Sensitive Prostate Cancer: Data From ENZAMET and ARCHES

EP: 16.Metastatic Hormone-Sensitive Prostate Cancer: Data from TITAN and PEACE-1

EP: 17.Educating Patients on Treatment Options in Metastatic HSPC

EP: 18.Novel Treatment Modalities in Metastatic Hormone-Sensitive Prostate Cancer

EP: 19.Overview of the Metastatic Castration-Resistant Prostate Cancer Treatment Paradigm

EP: 20.Metastatic CRPC: Advent of PARP Inhibitors

EP: 21.Practical Application of PARP Inhibitors in Metastatic CRPC

EP: 22.IO Therapy in mCRPC and Clinical Pearls

Transcript:

Alan Bryce, MD: There’s a lot of studies in this space. I’m going to give Dr Posadas the task of starting us out. Let’s start walking through these studies, and we’ll split it up among all of our faculty here. Dr Posadas, why don’t you walk us through talking about the triplet therapy with darolutamide, ADT [androgen deprivation therapy], and docetaxel? What are the data supporting this?

Edwin Posadas, MD: The ARASENS trial has been a very big deal for our field. It’s a large trial with over 1300 patients, so we’re talking about the ability to dive deep into this. When we first heard the data some time back about improved overall survival, that resonates strongly with the field, that the triplet was more effective than a doublet of just ADT with chemotherapy alone. It left us with this question that you had asked earlier Dr Bryce, who do you give chemotherapy to? I think Dr Lowentritt spoke very nicely to that. That becomes the sticking point. For the ARASENS trial, it was decided that everyone was going to get chemotherapy regardless of the arm you were on, the question is whether the addition of darolutamide made a benefit. The answer was yes, but many of us in the academic field got a little nitpicky with that answer and wanted some details. What was nice is [Maha] Hussain, [MD, FACP, FASCO,] was able to present some additional data that shed light, or at least sparked a whole new set of conversations over this field.

Patients were reanalyzed from the standpoint of high versus low volume. I think we were all very...seeing high volume patients benefit from this type of therapy. It was interesting to see that, at least statistically speaking, the low volume patients also had a benefit. I looked at the curves personally at the meeting and said, they look close to one another, but I guess the tail kind of separates out. The hazard ratio ended up being quite similar between the two, it was 0.69 and 0.68, so a 31% and 32% benefit whether you were high or low. Then a step further was taken, looking at high risk versus low risk patients, where again, there was benefit in both the high and low risk subgroups. I was even more taken aback by the fact that the low risk metastatic hormone-sensitive patients had a greater benefit proportionally, with a hazard ratio of 0.62 versus 0.71. I think a lot of us are talking about what this means at this point for these patients. We come back to the point that within the context of the ARASENS study, chemotherapy was already a foregone conclusion. In a de novo population, especially a higher risk group, that makes sense. I think a lot of us would say, I’m comfortable at least considering the triplet or some intensified therapy for de novo high volume patients. What we do with the lower volume patients, low volume high risk, maybe we think about it. But the low volume low risk, even though the data are there in this trial, I think we still need to know more.

Perhaps we will have more answers because one thing a lot of us have been thinking about is, how much of the triplet is driven by the chemotherapy and how much of it is driven by the hormonal manipulation? Hopefully, with trials like ARANOTE that are coming forward, we will have better insight into that. Some people are even asking the question, do you even need the ADT around with how powerful these ARSIs [androgen receptor signaling inhibitors] or ARPIs [androgen receptor pathway inhibitors] are at the end? I thought it was interesting that within the ASCO GU [American Society of Clinical Oncology Genitourinary Cancers Symposium] abstracts this year, there wasn’t the…study looking at darolutamide monotherapy in the hormone-sensitive population that suggested it’s quite active. I don’t find that surprising. There have been studies like that with enzalutamide, and we’ve done that with bicalutamide back in the day. These are options we need to know a bit about to put on the table, because as the panelists have said, we deal with a very heterogeneous group of patients. Being able to navigate their toxicity and their benefits becomes critically important.

Alan Bryce, MD: Absolutely fair. We can say without any question that the addition of darolutamide to a docetaxel, ADT backbone improves outcomes in all patient populations. It was tested in the ARASENS study, unequivocally, the addition of darolutamide is a positive. But does everyone need docetaxel is the open question.

Edwin Posadas, MD: I think that’s a 100% right.

Elisabeth Heath, MD, FACP: Having performance status and a frailty appearance could help us decide chemotherapy fitness. I again refer to…as she was thoughtful to create a scale. Sometimes when we need to count the points and ask, how much trouble are they going to be in, things like falls and the wibbly wobblies do count as a point. For example, if you’ve had a fall within 6 months, all of a sudden your risk goes up; if you’re older, your risk goes up. If you’re getting a genitourinary treatment, ie, docetaxel, the scale also fits for GI [gastrointestinal] drugs, so if you’re GI or GU, you get a point. Every one of these gets you to a level where you could have a bit more thoughtful discussion among your colleagues as well as your patients to say, with the numbers here I’ve tallied, the percentage, let’s say it’s a 75% or 80% chance you’re going to be in trouble, ie, grade 3 to 4 to 5 toxicity, you might say right then and there, maybe this is not a good idea. Not that you look bad, it’s just look at all these parameters starting to eat up the thought process of maybe you shouldn’t get it. I think somewhere in there, we never do that in a prospective way. But I use that scale to get to a certain percentage of how likely you are going to be in trouble. I think it helps the patient figure that out in a way that is a bit outside of what we talk about. For real-life practice, I think we need to use all the tools we can use to help make this decision.

Alan Bryce, MD: Fair, absolutely.

Tian Zhang, MD, MHS: Could you tell us, is there a website with that nomogram? Or is it just from the publication that was there?

Elisabeth Heath, MD, FACP: Yes, it’s from the publication, it’s a JCO [Journal of Clinical Oncology] article maybe about a decade ago. I consider that work that she’s done her legacy. It’s phenomenal insight, and she was such a well-known geriatric oncologist. That’s a lot of our patients too. If you’re in that 62-year-old pot, you don’t get a point because that’s not part of her scale. I’m certainly happy to share that with you. If you Google it, like many of us will, the graph just pops up; it’s a terrific resource. Sometimes when you’re trying to articulate the experience we all have on this panel, to let’s say our trainees or even those who see a lot of patients but maybe don’t see a ton of patients with prostate cancer, it’s easier for people to be able to put that into some sort of context.

Tian Zhang, MD, MHS: To your point, when we’re thinking about patients for docetaxel candidacy, the trial was patients who were good candidates for docetaxel, and it was enrolled in an era where we had standard of care abiraterone also available for our patients. So the patients who went onto ARASENS were what most people were thinking were good docetaxel candidates. In real-world practice, not every patient is going to be a good docetaxel candidate. I totally agree with you.

Transcript edited for clarity.