Metastatic CSPC: Educating Patients and Addressing Unmet Needs

EP: 1.Overview of Prostate Cancer and Treatment Modalities

EP: 2.Case 1: A 59-Year-Old Man With Nonmetastatic CRPC

EP: 3.Nonmetastatic CRPC: Importance of Patient Risk Status and Genetic Testing

EP: 4.Frontline Treatment Approaches to Nonmetastatic CRPC

EP: 5.Practical Advice on Novel Imaging Strategies in Nonmetastatic CRPC

EP: 6.Factors in Selecting Therapy for Nonmetastatic CRPC

EP: 7.Optimizing Management of Nonmetastatic CRPC: Darolutamide Therapy

EP: 8.Case 2: A 72-Year-Old Man With Metastatic CSPC

EP: 9.ARASENS Trial: Darolutamide-Containing Triplet Therapy for mCSPC

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EP: 10.Metastatic CSPC: Educating Patients and Addressing Unmet Needs

EP: 11.Case 3: A 70-Year-Old Man With Metastatic CRPC

EP: 12.VISION Trial: 177 Lu-PSMA-617 in Metastatic CRPC

EP: 13.Testing for Germline/Somatic BRCA Mutations in Metastatic CRPC

EP: 14.PARP Inhibition in Metastatic CRPC: The PROfound and TRITON2 Studies

EP: 15.Looking Toward Future Management Strategies in Prostate Cancer

Transcript:

Alan Bryce, MD: I think maybe we can ask the first 2 questions together. Eleni, how do you counsel your patients about the role of chemotherapy in this setting?

Eleni Efstathiou, MD, PhD: It's usually one of those very long first meetings where you go through all the potential options— leaving out ADT [androgen deprivation therapy] alone, and you present the different agents and the pros and cons. The question about chemotherapy—it's the dreaded word—but what helps is, once the patient has the understanding that this is a 6-cycle-and-out process, [then] we're done. And if it happens early on, we also always comfort the patient when we have this discussion; we are going to go to full dose. It's very likely you will have no problem, but we will be there if need be. Let's say [they are of] Asian descent, and the like, to cut down on that. You have to babysit these men. I know we're speaking to oncologists who are not necessarily the only practicing GU [genitourinary] oncologist. Prostate patients are a completely different breed. They're vulnerable even when they look like they're doing CrossFit and running around more than we are. It just the nature of the beast. The fact that they’re losing their testosterone makes them very vulnerable. And that is where a lot of time is spent: describing that, yes, we saw it with the CHAARTED [Chemohormonal therapy versus androgen ablation randomized trial for extensive disease in prostate cancer trial] data. We saw that dip in quality of life and they literally tell them, “Life will suck for 3 months, we will be there for you after that; we'll be fine.” But now with the addition of darolutamide, I had a man who I was struggling trying to start. He was falling apart. He had been admitted. I met him in inpatient because he had gone into diabetic ketoacidosis. And at the same time, [he had] high volume, highly symptomatic constitutional symptoms. The guy is on docetaxel and darolutamide—which I started just when the press release came through—and he's doing great. But at first, I give them the worst-case scenario and we take it from there. That's kind of my approach: no sugar coating. It's chemo. You're older men – let's do this. Again, it might be a little bit of a tougher approach to life, but it usually works.

Alan Bryce, MD: You started out talking about how they need to be babied, and then you ended up so tough. That was a transition.

Eleni Efstathiou. MD, PhD: Kind of like, “We're here for you. That's how we babysit you. We'll see you every week. We'll be on the phone with all of that, we will hand-hold you, but it's not going to be pretty.” They know. The younger guys do well, but when our older patients come on, it's harder. We agree on that.

Alan Bryce, MD: Dan, what about unmet needs in this space?

Daniel Landau, MD: Well, we're getting better, thank goodness. Just a few years ago when I told everybody I was going to be a GU oncologist, they looked at me and said, “Why? You guys don't have anything that you can offer patients.” Thank goodness, we've made quite a few strides in this setting, but making strides come with certain challenges. One is understanding sequencing, understanding the exact value of chemotherapy as we're debating, hopefully, [whether] it's going to be less and less as time goes on. But 1 thing you mentioned is that still the best survival data does come from combination therapy. We're still stuck in the chemotherapy world, for now; hopefully moving away from this, but there are a number of other exciting things, hopefully, on the horizon, whether that's going to be more PSMA [prostate-specific membrane antigen]-directed therapy, whether it's going to be other combinations on the horizon. I think the future is very bright as opposed to what my colleagues told me just a few years ago.

Alan Bryce, MD: What I like to tell patients when I give these talks about mCSPC [metastatic castration-sensitive prostate cancer] is this concept of treatment intensification recognizes that since 2015, we're on an unbroken winning streak of 9 straight studies. Intensification works, and we're late to this game. Look – intensification with multidrug therapy was proven with MERCK back in the seventies. Come on. And it takes 45 years for prostate cancer to start to do the same thing. The research in this space is going to be gangbusters for the foreseeable future because every drug that is yet to be tested in first line is going to be tested in first line. We're going to be doing various combinations; obviously PARP inhibitors are coming into the first line. Lutetium-177 is coming into the first line in clinical trials. And I don't think we're about to slow down. We've gone to 2 drugs, we’ve gone to 3, we’re going to try various combinations. I think part of the message in this space is please think about the clinical trials, because there are a lot of great questions to be asked and answered in this space. And if we take it 1 step further, my real hope—and I alluded to this with the way I practice—we're going to be somatic testing every patient and defining the different genotypes with different treatment pathways per genotype. Just like up-front breast cancer where it's ER [estrogen receptor]-positive, HER2 [human epidermal growth factor receptor 2]-positive, triple-negative. That's what prostate cancer has to look like. To me, that's where I hope we are 5 years from now.

Eleni Efstathiou, MD, PhD: And actually, institutions like where I'm at, when I proposed exactly that they embraced it like up-front, let's just throw the whole sequencing and put it in a cloud and have it to further explore it. That's the way to go and not butterfly-collect those tissues for some use at some point, which is what is the traditional. I really liked your point, Alan, about how late we are in the game. I think that I'm seeing the light being you're in this amazing institution and I'm now back into a great general hospital, and I'm seeing all these 90-year-old men who now are looking into life with still a lifespan. Back in the eighties and nineties, you'd say: 65- and 70-year-old, and you would say, well, there's no expectation. These have changed thanks to the advent of modern medicine. And this is helping us just to joke a little bit about it. Today, I had three 90-year-old patients. One of them was ready to go to his South-of-France escapade, another one on a Kenya visit to see the elephants. It is like they're living the life and they have the expectation to live well and longer. That is what has changed, literally.

Transcript edited for clarity.