Tian Zhang: Thanks for having me, Zach.
Zachary Klaassen: So we know we've made a lot of progress in mHSPC in the last decade or so, but that transition to mCRPC, when that starts to happen, how do you have these conversations with your patients?
Tian Zhang: Yeah, hard to do, but certainly very common in our practices for metastatic hormone-sensitive prostate cancer to start having castration resistance and progressing despite even the best options that we have in the frontline setting. So we have those conversations even upfront when we talk about putting them in the management of doublets and intensifying treatments, and we'll have preempt that conversation say, some people do great, some people not so great, and biology, prostate cancer is such that with treatment pressure, sometimes they'll turn in more into castration resistance. And so having that conversation a little earlier as they're sort of getting settled in year one of hormone-sensitive disease will help that conversation later on when it has to happen for hopefully a select population patients who develop castration resistance.
Zachary Klaassen: And you're right. It's a hard conversation. It's not fun. I mean, patients, they like to see the overall survival curves, but they like to see that time to mCRPC curve because as we know, that's a lethal form of prostate cancer. Treatments have to change. So it's important to have those discussions. I like how you laid out that you have it early. I just want to back up a little bit. The big discussion these days is doublet versus triplet. How are you selecting your patients at that mHSPC setting?
Tian Zhang: Sure. Well, I'll walk you through a common scenario in my clinic, which is a patient who comes in with metastatic hormone-sensitive disease. Oftentimes nowadays, they're coming in with a PSMA PET scan because it's so available that many of our patients are receiving that as their first imaging study. I always like to think about folks in the CHAARTED high-volume versus low-volume criteria. So with that first visit, we're getting them started on hormone deprivation. We're having them acclimate to that within the first month or so. And I use that time to get my bone scan and sort of risk stratify. And then I start having those conversations of, "Hey, we'll likely be adding more treatment despite getting you on ADT. This is our first approach, backbone of our treatments, and we'll likely be adding on either an oral therapy or maybe an oral therapy plus a chemotherapy." And if we set those expectations up early, then patients know what to expect. They come back in about a month after they start their ADT and now they've settled in, their testosterone is in castrate range. And at that point, I can have the conversation of, "These are the drugs that are available." And we're often thinking about genomic risks as well. So we're getting that genomic data, "Here's your bone scan result, here's what we can do now." So I think it's really important now that we have AMPLITUDE data out in the hormone-sensitive space.
We have PSMA lutetium also coming into the hormone-sensitive space with PSMAddition readout, that we have some of those targeted conversations early, and then we can intensify their treatment. So they come back in, we have their bone scan result, and then we can start the conversation. "Are you high risk enough that chemotherapy makes sense in this particular setting?" And if it does, and I think our patients, they want to do what's going to get them the best outcomes. So if it's a doublet, we're talking enzalutamide, apalutamide, darolutamide, and picking with side effect profiles. I hardly reach for abiraterone in that setting. If it's a triplet, then putting in the docetaxel for the patients with high-volume criteria.
Zachary Klaassen: Yeah, absolutely. I think I like how you laid out that this is several visits. It's not something you have to lay on the patient at the first visit. I think that's important too. And something I've adopted in my clinic as well based on discussions with you guys who deal with this a lot. I think when we look at that transition to mCRPC, is there a different conversation as you're getting to that point of mCRPC based on whether that conversation started with a doublet or with a triplet?
Tian Zhang: I think if you started with a triplet and the pattern of progression is that they've had a really nice response and now it's a year or two later with metastatic hormone-sensitive disease, we are in good shape that many patients respond for many years, but now as they're progressing, then you can have that conversation of, "Remember what chemo felt like? You responded beautifully, let's think about it again." If it was a doublet that they started with, then chemotherapy is a little harder for them to wrap their heads around. But I think in the right situation, if disease is progressing quickly, especially on radiographic features, chemotherapy is likely a next-line option for castrate-resistant disease. And then we're thinking about all of our trials for patients to be exposed to novel therapeutics in those settings.
Zachary Klaassen: Yeah, great points. I think the topic of our discussion is creating a smooth transition to mCRPC. So for the listeners out there, maybe they're seeing some prostate cancer, they're seeing a lot, they're trying to think about factors to look for and who those patients we should be looking for. Is there patient-specific factors or maybe disease-specific factors where you're thinking this is starting to go towards mCRPC?
Tian Zhang: Yeah, that's a great question. And we follow people over time, so we get a lot of PSA values over time. And that is probably our first inkling of castrate resistance is when their PSA starts rising and they've been on the hormone suppression for at X amount of time. So ongoing hormone deprivation, PSA starts going up. Usually, the patients aren't feeling anything and they're in our clinics, they're on their doublet and they're feeling well and we just get this lab value that's continued to rise. And in those settings, there can be a lot of anxiety. We will redo their scans for sure if they haven't been getting ongoing scans and figure out, is there new disease? We will think about continuing what they've been responding to. So oftentimes in my clinic, we'll get some PSMA PET scans at this point. If there's only a couple of spots of progression, oligoprogression, we'll think about continuing their treatment while doing some radiation to those spots of oligoprogression. And maybe that helps smoothen the course because they're not treating and changing all the systemic therapy all at once, but rather adding a little bit of radiation in, get you some more time on your oral treatment and then move on to other systemic therapy.
Zachary Klaassen: Yeah, very helpful. Great discussion with you. Anything we haven't hit on you want to talk about? Any take-home points for our listeners?
Tian Zhang: Well, I do think there's a lot of good treatments coming down the pipeline for castration-resistant prostate cancer. There are some really promising antibody-drug conjugates, bispecific T-cell engagers, AR degraders. So I'm really hopeful that we'll see more mechanisms of drugs that are useful. And ultimately, in my practice, and I'm sure yours, we are seeing patients with metastatic hormone-sensitive disease live many years with their disease. And so my goal for many of my patients is to help them live longer and better and with preserved quality of life. But I do think that when we sequence these life-extending therapies, we can get our patients to live an optimal life and really make the most of their time. And it can be a very long time for a patient with hormone-sensitive that becomes castrate-resistant prostate cancer.
Zachary Klaassen: That's great. We had a great decade since STAMPEDE and CHAARTED and hopefully the next decade will be just as exciting as you laid out. So thanks for joining us on UroToday, Tian.
Tian Zhang: Thanks, Zach.