Maximizing Survival in Metastatic Hormone-Sensitive Prostate Cancer: The Role of Triplet Therapy - Kelvin Moses

April 15, 2024

Zach Klaassen and Kelvin Moses discuss the continuum of care for metastatic hormone-sensitive prostate cancer, focusing on triplet therapy. Dr. Moses highlights the ideal patient profile for this treatment, emphasizing collaboration between urology and medical oncology. They stress the manageable nature of chemotherapy and its finite duration. The conversation extends to disparities in prostate cancer care, particularly among African-American patients. Dr. Moses underscores the importance of aggressive treatment for younger patients and the reassuring response of PSA levels. They also touch on the significance of time to castration-resistant prostate cancer and fostering collaborative relationships in patient care. Overall, they advocate for prioritizing aggressive upfront treatment to maximize survival and quality of life.


Kelvin Moses, MD, PhD, Director of the Comprehensive Prostate Cancer Clinic and Associate Professor, Vanderbilt University Medical Center, Nashville, TN

Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Well Star MCG, Georgia Cancer Center, Augusta, GA

Read the Full Video Transcript

Zach Klaassen: Hi, my name is Dr. Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. And I'm pleased to be joined today by Dr. Kelvin Moses, who is a professor of urology at Vanderbilt University Medical Center in Nashville, Tennessee.

Thanks so much for joining us today, Dr. Moses.

Kelvin Moses: Good to be here.

Zach Klaassen: So today we're going to talk about a passion of both of ours, and this is the continuum of care for metastatic hormone-sensitive prostate cancer. And so we both see a lot of advanced prostate cancer. Specifically, today's discussion will be around triplet therapy. So, in your practice, who's sort of the ideal patient for triplet therapy in 2024?

Kelvin Moses: Yeah. So if you look at the major trials that have come out over the last couple of years, the patients who were included were otherwise fairly healthy. So they had a performance status of zero or one. They did allow for bone pain as long as it could be treated. The vast majority of the people in those trials had de novo metastatic disease. If you look at a couple of them, it was over 80%. So it might not be quite known if patients who develop it after treatment or who have been on hormone therapy for a while benefit. But certainly, those with de novo disease are probably the best ones. And then obviously, they need to be fit enough to go through chemotherapy. And with prostate cancer, as we all know, because it's a single agent, it's much better tolerated than most cancers, but still, patients need to be fit enough to undergo chemotherapy.

Zach Klaassen: And one thing I mention to my patients, and you probably do the same, is that this is not chemotherapy until you have toxicity or you die. This is six cycles, you're done in roughly four, four and a half months. Is that something that you bring up with your patients as well just to sort of get them on board with that aspect of it?

Kelvin Moses: Yeah, I really emphasize it's a single agent once every three weeks, six times. And so even if they're getting hit with it, it takes them a couple of days to recover. But my guys who are working still work. My retired guys are still going out on the golf course. So it is not that it's just bowling them over and like you said, it is a finite time.

Zach Klaassen: Yeah, for sure. So once you identify these patients, how are you collaborating with medical oncology? I'm assuming they're given the chemotherapy. How are you coordinating with medical oncology from the university level?

Kelvin Moses: And it is really a team approach. So patients who see me first, I'll usually coordinate the hormone blockade part of it, and then I have colleagues who are in the clinic at the same time, so I can send them there or they may already have an appointment. We don't have one clinic where everybody's there, but we practice in a multidisciplinary fashion and they will send patients to me for androgen deprivation, whether it's injectable or even if they want surgery, if they want orchiectomy. And so we play nice in the sandbox, as I like to say.

Zach Klaassen: That's kind of the theme we get from the academic centers, that there's mostly good collaboration between the two. And I think you kind of took the next question out of my mouth. It sounds like you're giving the majority of the ADT plus darolutamide and they're doing most of the chemo, and you're seeing both patients, whether they see them first or you see them first?

Kelvin Moses: Yes, we usually share them. Now I know there are some who go to medical oncology first and they can handle everything, and that's perfectly fine. But because we have the comprehensive prostate cancer center here at Vanderbilt, we do see a fair amount of patients with advanced prostate cancer. So again, yeah, we do prescribe the oral medications as well as the injectables or surgery. We're lucky here too, we have a specialty pharmacy, so they really coordinate a lot of it just to make it easy for the patients. They deal with the insurance companies. They deal with the industry partners. And so they bring down costs tremendously. Most of my patients aren't paying anything out of pocket or less than $100 a month, which is great. These new therapies are very expensive.

Zach Klaassen: That's a good point. I'm going to jump off that a little bit. So when you get these patients rolling, are the APPs seeing them? Are the residents seeing them? Are you seeing all these patients? How does it work once you get rolling? Because it sounds like you have a great team set up there from all the insurance and everything else along with that as well.

Kelvin Moses: Yes, we have a good process. It's one of two attendings. We do have an APP, and she will see new patients, but typically a lot of our guys are kind of in cruise control, so she'll see them with undetectable PSAs, no symptoms. I do have a resident in the clinic with me, and I'll still go see the patients. But for the patients who are in cruise control, it's really a quick visit because, as we'll probably get into, most of these medications are actually pretty well tolerated. So unless they're having significant side effects or the PSA is rising for some other reason, that's a really kind of a chip shot visit.

Zach Klaassen: For sure. I want to talk a little bit about both of our practices being in the south of the United States, which still has tremendous disparities, not just when you have cancer but also just in screening and patients coming in. And so I know you and I have talked many times about how several times a month, an African-American, 47-year-old comes in, he has got a PSA of 1600. And those listening in other parts of the world, this does happen in the United States.

When you see these patients, are these patients all getting triplet therapy? Are they on board with it? How are you counseling these young African-American men specifically?

Kelvin Moses: Yeah, so I tell them, look, you have aggressive disease. It's not immediately fatal, but it can be and maybe will be. Their life expectancy otherwise would be another 30, 40 years. So I say we should probably be as aggressive as we can upfront in order to prolong the time before new metastatic disease shows up or castration resistance develops. So I go through all the options. I say single, double, triple therapy. I quote all the data, but then I tell them, I say, hey, look, what is your priority? What is important to you? And if as close to we can't cure, but as close to undetectable disease as possible for as long as possible, then I say, we should really go at this. You're a young healthy guy otherwise. You can live with metastatic cancer for years. But what we want to do is make sure we maximize that survival while maintaining your quality of life. These guys are still in their working age, they're still providers for their homes. So we want to keep them productive but also get them as well treated as early as possible. So I will definitely emphasize triple therapy and let them know that beyond double therapy, the adverse effects are not significantly different.

Zach Klaassen: One thing I want to get your opinion on too is we've seen some post-hoc data from there since talking about PSA basically undetectable within 9 to 12 months, and sort of those patients doing remarkably well. So are you using that particularly in these young men to say, hey, it's almost like our test is cancer patients, we got to hit you hard. You're younger than most. This is why we're doing it, and this is why with the PSA undetectable rates at roughly 9 to 12 months really do make a difference. Are you talking to them about that as well?

Kelvin Moses: Yeah. So the benefit with this triple therapy, you get this rapid reduction in PSA, durable response of PSA. And so yeah, that's what I tell them. I say if we're out one or two years and still with an undetectable PSA, you get the every other year bone scan just to make sure and things are less avid, all the better. These guys that come in, that PSA, not to use the phrase lightly but they kind of live and die by that number. And so to have that reassuring response is really good for disease management, but also for a little bit of peace of mind.

Zach Klaassen: And I think another question I want to ask you on that same train of thought is we know the time to CRPC kappa marker curves, you could drive a truck through those curves. And I think from a clinical standpoint, talking to the patient that's actionable data because that means PSA is going up, we just talked about PSA anxiety, and it also means another treatment. So are you using time to CRPC as well when you counsel these folks?

Kelvin Moses: I do. I probably emphasize overall survival more just because that sort of question starts to get a little esoteric for them when you start talking about the development of castration resistance. But I do bring it up because I say if and when we progress to the next stage, these are our options, but the window starts narrowing a bit. So the longer we can put that off, the better. I always give them hope and options. And even as we know, plenty of trials in the MCRPC have shown extended survival with multiple classes of medications. But again, with metastatic disease you're talking about five to seven years, some of the young guys, 8 to 10 years. But when you get to CRPC now you're talking two, three, four years. So I definitely let them know that that's our goal.

Zach Klaassen: Yeah. We've talked already about the collaboration with medical oncology and both of us have great relationships. For those out there that may be in community practice or even in academic practices where that relationship isn't quite as good, what's your message to folks in terms of this multi-D approach, really putting the patient first and fostering that collaboration if they don't have it already?

Kelvin Moses: Yeah, I think prostate cancer in general, up until really CHAARTED came along, or maybe Sip-T, once guys progressed to hormone therapy, urologists sort of gave up on those patients and said, 'Hey, you're going to get shots the rest of your life and you're going to be dead within three years.' So, we have to sort of reclaim our patients because we're the ones who saw them initially, we did their surgery or we sent them to radiation, we're still following their PSAs. And so those patients have developed trust in us. And I think that's one of the things we can communicate with medical oncologists and say, 'Hey, we know these patients well, we're happy to see them with you. If they show up with hematuria or urinary obstruction or they need perc tubes or whatever, we can work with you.' And again, on the medication side, at least in the academic world, my salary doesn't change if you're on Enza or Daro or Docetaxel.

So I think if you can establish that, 'Hey, I already have a relationship with this person and I can work with you with them and maybe help explain things,' then I think that would improve the relationship if there isn't one already or if it's been adversarial before.

Zach Klaassen: Yeah, that's well said. Great conversation. Anything we haven't hit on that you want to talk about, maybe a couple of take-home points for our listeners?

Kelvin Moses: Yeah, I think really the proof for triplet therapy is out there and you can parse the three different studies, PEACE, ARASENS, ENZAMET and say, 'Okay, is one better than the other?' But without a head-to-head trial, you don't know that. But particularly if you look at ARASENS, a 33, 36% reduction in the risk of death, I mean that's significant. And that's where both groups in all the trials had subsequent therapy. So there's something to be said about that initial aggressive treatment with chemo and dual hormone therapy that's really helping these patients. And again, once they're off chemo, they're just sort of on cruise control with hormone therapy, so we should really be emphasizing this.

Zach Klaassen: No, that's fantastic. Dr. Moses, thanks as always for your time and for your expertise today.

Kelvin Moses: Yeah, always good to see you.