Case 1: Patient Choice in Initiating AR-Targeted Therapy in nmCRPC

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Neal Shore, MD, FACS:It’s the spectrum. My pushback to you is that you said, “I’m just going to tell you about taking the class of the drug.” But I’ve been doing some more work on this notion around what’s calleddiscrete choice experiment. For patients to become more involved, in saying to them, “Look, I’m going to give you an extended number of months for a MFS [metastasis-free survival] or overall survival, but your trade-off is fatigue—grade 1, grade 2, grade 3.” Or, “Your trade-off might be some blunting of your cognition.” Or, “The trade-off may be GI [gastrointestinal] adverse effects.”

And I think we have not done, historically, a good enough job in explaining this to our patients. Patients have heterogeneity the way we have heterogeneity. You may be very aggressive. I may be more conservative in my desire to institute another line of therapy. Some patients are very conservative, or are more risk-seeking in taking on certain adverse effects. So that’s why I think in the field, and all of GU [genitourinary] oncology, quite frankly, in much of what we do, we need to do better. We need to have evidence. Do the studies. Do the trials like we’re all participating in. But we also need to be explaining these choices to patients better.

Kenneth Kernen, MD:I’m sorry to jump in, but maybe the idea is: We should be tracking it better. Whether we have an educational system that tracks FACT-P [Functional Assessment of Cancer Therapy-Prostate] or something, because 1 of the other problems is most of these guys, when you say, “Hey, how are you,” are going to say, “I’m fine.” And their spouse may say, “Hmm, not so much,” because they are having some neurocognitive issues, or some blunting, and adverse effects. So maybe part of our role in doing that is we should be doing a better job tracking it.

Alicia Morgans, MD:I completely agree. I think that’s both in clinical practice and also in the trials. I guess to stay on this blunting idea, things like FACT-P are actually incredibly blunt instruments to try to understand the nuances that are affecting people who are “asymptomatic” in this nonmetastatic CRPC [castration-resistant prostate cancer] population. And what I find so frustrating is that the clinically meaningful difference, for example, for FACT-P was actually defined in a very different population. This is a population with metastatic CRPC. These guys had been through things that nonmetastatic CRPC patients have never experienced and won’t probably experience for years. And so, what’s meaningful to them and the difference they’re willing to tolerate could be completely different. So I think as a field, I agree with you. We do need to reassess the measure by which we are understanding these changes, and really make a decision to move in a direction to be more precise.

Jorge Garcia, MD:Especially, and I agree with that… We know the M0 space is sort of a space that we may not access with emerging technology—with imaging such as fluciclovine PET [positron emission tomography], PSMA [prostate-specific membrane antigen] PET—and especially when these agents are getting moved completely to the frontline setting. People with metastatic disease, actually, even in combination with radiation therapy in the neoadjuvant/adjuvant space. So it is very likely that our patients may actually start seeing this class of agents even upon diagnosis, right? And they may stay on this class of agents for longer period of times, exposing them to significant risk.

Alicia Morgans, MD:Absolutely. As we think about this patient and about the course that he’s had, I’d love to hear some closing thoughts. What are your thoughts on this patient; and more generally, on the treatment of nonmetastatic CRPC, Jorge?

Jorge Garcia, MD:A lot of people ask me, “Jorge, how do you make your decisions?” And a lot of people say, “Well, it 1 feature, 2 features?” It’s the whole case. This case is more than a doubling time, in my opinion. But I think that doubling time is extremely important in the context of a rising PSA [prostate-specific antigen] syndrome, meaning after you fail biochemically and through the natural history of your disease. But I also want our audience to actually realize that it’s not about a doubling time. It’s about the entire structure behind that—his pathology, his inability to achieve an undetectable PSA, and his failure early on; and perhaps even that he actually may have some genomic abnormalities that we haven’t even talked about yet but may be important for us to tap into because they may be used for therapeutic purposes down the road for this patient.

Alicia Morgans, MD:Absolutely.

Kenneth Kernen, MD:I would agree with Jorge on all of those things. I also think 1 of the things we didn’t touch on, that I think is critically important, is bone health and the overall health of the patient. One of the things we try to do from the get-go, once we institute ADT [androgen deprivation therapy] is get him on calcium and vitamin D. We put him in an exercise program. We have a program in our multidisciplinary tumor board back home where they can go for a consult, because I think that’s important, and get them on some sort of bone health agent as well. In a lot of these clinical trials, if you look at the amount of patients who actually got bone health agents, it’s shockingly low—10%, 11%. So, again, I think for someone like a patient like this who has not done well all the way along, it’s critical to probably get this guy on bone health treatment early on as well.

Alicia Morgans, MD:Absolutely. Start early, and make sure that it continues. What do you think, Neal?

Neal Shore, MD, FACS:That’s a really good point. I think in SPARTAN and in PROSPER, the use of bone health agents is about 10%. In ARAMIS, interestingly, it was about 3%.

Kenneth Kernen, MD:Right.

Neal Shore, MD, FACS:In both arms. It’s balanced. And yet, they had fewer fractures, and they actually have balanced falls. I tend to, in somebody like this patient who appears to clearly have aggressive disease, who has good performance status, and if accessibility is not an issue, I believe in treating these patients and offering them the opportunity for therapy. And I do believe in looking at the doubling time. It’s very important. I use the Memorial Sloan Kettering Cancer Center calculator. It takes literally 30 seconds to put in 3 to 4 data points, and the answer is there for you. And if it’s north of 10 months, way north of 10 months, I don’t start therapy. I tell the patients I’ll continue to follow them with PSA until they reach that point. I think this is really a good case to show the options we now have. I do think, again, it gets back to us learning more about this whole issue of, it’s more than just fatigue. It’s a lot more involved. It’s more complicated. We need better validated tools, as you said. Things are now kind of blunt. I think there’s going to be some very exciting trial data that are going to be forthcoming in the near term.

Alicia Morgans, MD:Absolutely. To reiterate, patient selection is key. Using the PSA doubling time to help make those choices is important. Things like the Gleason score and time to recurrence also really help us make the decision for initial ADT. And then PSA doubling time, again, when we think about adding these agents. But at the end of the day, maintaining patient quality of life, improving it if we can, is going to be critical for this population, even as it evolves, and as we see imaging evolve over time. I really appreciate your thoughts on this.

Transcript edited for clarity.