Advancing Treatment Strategies in mHSPC: Addressing Disparities and Optimizing Care

A roundtable discussion, moderated by Pedro Barata, MD, of University Hospitals, highlighted the evolving treatment landscape of advanced prostate cancer, including hormone-sensitive prostate cancer (HSPC) and castration-resistant prostate cancer (CRPC). The panelists analyze expanding treatment intensity, the utilization of androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs), and integrating patient-reported outcomes (PROs) in care. Dr. Barata was joined by Andrew Armstrong, MD, MSc, of Duke University School of Medicine; Cora Sternberg, MD, of Weill Cornell Medicine; and Evan Yu, MD, of UW Medicine.

In the third part of this series, disparities and the optimization of care is discussed, along with the use of ADT and ARPIs.

View the next segment of this roundtable series: Balancing Treatment Intensification, QOL in mHSPC: Insights on Patient Management, Bone Health

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Dr. Barata:
It’s been fantastic, thank you for that. So we talked about PET, we talked about finding oligometastatic maybe in some of these men perhaps. So we are getting into the area or setting of the metastatic hormone-sensitive disease. It has been defined by conventional scans, CT scan and bone scan. That is changing with PET scans. We are finding more disease, we’re upstaging patients, we’re finding more disease, perhaps in a lot of them, metastatic disease. And of course, the field has changed dramatically in the last eight, nine years. First with chemo, then with different novel moral therapies, RPIs, and in some situations triple therapy.

And we have been reported over time how our practice, when I say our practice, referring to US, has changed. But the real world data still suggests that about half of men are still not offering, let’s call it treatment intensification, meaning ADT castration, ARPI plus/minus chemotherapy, despite all the phase three trials that we have demonstrating a benefit. So I’m going to ask the first question. Cora, I’ll start with you. Do you still see those men, maybe second opinioners, who come to see you or someone from your team? They’re still coming treated in that setting with ADT or ADT with a first generation anti-androgen, which is now we consider ADT alone. Do you still see that men? Is that the 50% real where you practice. And if it is, what are your thoughts? Why is that still happening?

Dr. Sternberg:
I know that that’s still happening, and it’s still happening primarily in the community. Not necessarily in the main academic centers. Because in the community, doctors don’t just take care of prostate cancer, they take care of breast cancer, prostate cancer, bladder cancer. They may not be every kind of … Lung cancer, colon cancer. They may not be up-to-date with all of the studies that we have with metastatic hormone-sensitive prostate cancer, showing that the combination with an ARPI is much better and that the patients live longer. They just haven’t read all those studies. They haven’t read every colorectal study, every prostate study, every study. So I think that that’s important. What’s interesting is that when patients are getting treated with PSMA PET, we don’t really have any data on that at all. All of these studies have been done with conventional imaging. I was trying to look and to find studies.

I even asked Andy the other day. There’s one study around that’s really looking, and I’ve been looking through PubMed. There’s no studies that are really … All of these studies, that were not done with conventional imaging. And then once, if patients come to you on ADT alone and on therapy, based on a PSMA PET, how do you follow them? Are you supposed to follow them with another PSMA PET or are you supposed to follow them with conventional imaging? But I think that the problem has to do with the fact that many of the drugs are not available in Europe and in many countries. They’re expensive, and many of the community doctors are not using it. So we know that many are treated also by neurologists. There’s some 50% of people that we know around the world that are treated with ADT alone. Perhaps not in my institution or yours, but that’s what’s happening.

Dr. Barata:
So Andy, you helped develop some of these data. Just to summarize really quickly. So we had CHART and STAMPEDE supported docetaxel along with ADT. Then we’ve seen LATITUDE and STAMPEDE for abiraterone. Then in 2019, we had your data, ARCHES, ENZAMET. We had TITAN supporting enzalutamide there and apalutamide there. And then more recently, we had the data for triplets with darolutamide, with the ARASENS trial, along with docetaxel ADT. And then PEACE-1 for docetaxel, abiraterone and ADT. That’s a lot of Phase III trials.

Dr. Armstrong:
And you got ARANOTE. Got ARANOTE as well.

Dr. Barata:
And then that’s perfect, ARANOTE, which I’ll ask you a little bit to remind us what exactly that read out at ASMO. So what else do we got to do? Because I feel like in every single meeting, we have updates in all these different trials and we have pretty clear, it’s in the guidelines. What are we missing, if anything?

Dr. Armstrong:
Right. We have a blessing of riches right now, as Cora mentioned, all this evidence as you just mentioned. I think one key step is implementation of this in clinic, and your own data has shown that there are disparities and access and costs and who prescribes it. That choice that you make, the predictors of not having access to these drugs are socioeconomic, which has tracked with race and ethnicity. The decision not to give a drug has been often observed in the community and community urology practices where it’s complicated.

But I think that’s increasing over time. In my practice, it’s like 95% of patients are getting doublet or more therapy. I think you’re preaching to the choir here, but we need to implement this work in the community. And whether that’s any ARPI, I think of them all is equally effective. But choices are going to be coming down to costs and toxicity and what’s right for that patient, and their drug-drug interactions and comorbidities. The decision on treatment intensification comes down to disease volume, whether they’re fit for docetaxel. There’s another form of triplet therapy, which is radiation to the primary. So if you have low-volume, synchronous disease, that’s triplet therapy. It’s level one evidence. And there’s already strong evidence that we need to now just educate the community about implementing.

Dr. Sternberg:
I think we need to really educate the community, but we also … Many don’t have specialized pharmacies, and that’s a huge problem.

Dr. Barata:
That’s a good point. So since you mentioned, Andrew, ARANOTE, can you please summarize the data really for our audience? Because my next question is it possible that some folks might get overwhelmed with all the options, they don’t know how to decide?

Dr. Armstrong:
I think we have a lot of options in mCRPC. Now, we have a lot of options in non-metastatic CRPC and we have those same lot of options in mHSPC. And at ESMO, we’ve heard the ARANOTE data from Fred Saad showing a significant delay in progression-free survival as you might expect with darolutamide, and a very clean sheet of toxicities as you have expected from other darolutamide trials.

It’s a very well-tolerated oral ARPI. It doesn’t penetrate the CNS, not a lot of hypertension or fractures or fatigue or falls. And so I think it’s got a very favorable side effect. Profile choices around doublet or triplet are now going to come down to which ARPI is the right and whether they’re high-volume and chemo-fit. I think all of them are right decisions. The wrong decision is not to offer those.

Dr. Barata:
Yeah, that’s a fantastic point. So Evan, I want you to walk us through. So many options. So we have ENSA, we have ABBI, we have APA, we have daro. I don’t know if you’re using chemo not in your clinic. Sounds like chemo alone is no longer center of care. If you do chemo, you do it along with an ARPI and ADT. You have the comment around DDIs. A lot of these trials have shown. All the efficacy endpoints are positive. You delay progression, you delay time to next treatment. They live long, patients live longer. But also quality of life seems to be preserved. So how do you present that to the patient? And by the way, how do you take the quality of life data in this context?

Dr. Yu:
Yeah, the first thing I do is I look at how does the patient present? Do they present with de novo disease? Do they present with recurrent disease, meaning they had radical prostatectomy or they had radiation to the prostate primarily in the past, and now they have recurrent metastatic disease? Because the prognosis is different there. I look at what the volume of disease is. Do they have high volume disease using the chartered criteria, which was actually an old SWOG criteria back from 1990, I believe. But which is having visceral metastasis or having four or more bone metastasis with at least one outside of the axial skeleton. So appendicular skeleton somewhere. That would put you in a high volume criteria. And so when you’re talking about triple therapy and use of docetaxel, yes, I do use it. But I tend to reserve it for patients who have de novo and high volume disease.

I think if you have a mix of de novo and low volume disease or high volume disease and recurrent, those are smaller subsets in the studies. I think it’s harder to definitively tease out the benefit. But de novo high volume, there’s clearly benefit. But the one thing I want to emphasize is the way the studies were designed, the ARASENS trial and the PEACE-1 trial. They were designed with the backbone of ADT and docetaxel. They were not designed with the backbone of a doublet of ADT and the ARPI. So it’s very clear that when you add that third agent, which is an ARPI, that there’s significant benefit for that kind of high volume de novo population. What we need to do as a field is we need to learn whether there’s really benefit to adding the docetaxel. And those studies are getting launched now, Alliance has a study right now with metastatic prostate cancer patients.

The focus is really looking at some molecular markers like RBp53p10. Do those patients gain more benefit from docetaxel. CCTG, the Canadians, and also SWOG have combined together. They’re planning on doing a study looking at starting with the doublet of ADT with an ARPI, and saying, “If you don’t get to an undetectable PSA, which tends to be a worse prognostic group, is there randomizing those patients to docetaxel or just continuing a doublet?”

So those are very, very reasonable studies to do. And here at ESMO, we actually saw some data, I believe it was from the STAMPEDE study, where they looked at using Decipher. And they didn’t find that Decipher yielded any predictive value with the ARPI, but it did with docetaxel. So not just prognostic value, but actual predictive value. And so applying something like Decipher to these couple new trials that I’m talking about, might be really interesting to further delineate who really needs that docetaxel and who doesn’t. Because we need to not just figure out treatment intensification and apply the data, but we also need to recognize that there are patients that were intensified that might not need it. Can we cull those patients out and be able to intelligently de-intensify people and save them toxicities?