Treatment Decisions for Patients with Metastatic Castration-resistant Prostate Cancer: A Retrospective Study of Real-World Experience - Tia Higano

Alicia Morgans invites Tia Higano to discuss data analysis amongst patients with mCRPC who were enrolled in the Flatiron Health prostate cancer registry from 2013-2017.  Findings include the discovery that 77%  of patients receive some form of life-prolonging therapy and that only 60% of the patients ever received either denosumab or zoledronic acid.  Alicia and Tia conclude by stating the importance of real world data and differences between academic centers and community centers.
Biographies:

Alicia Morgans, MD, MPH

Celestia (Tia) Higano, MD, prostate cancer specialist and professor of medicine at the University of Washington School of Medicine. She is also director of the Genitourinary Oncology Clinical Research Group at the University of Washington and a member of Fred Hutchinson Cancer Research Center.
Read the Full Video Transcript

Alicia Morgans: Hi, I'm excited to have here with me today, Dr. Tia Higano, who is a Professor of Medical Oncology at the University of Washington School of Medicine and the Fred Hutchinson Cancer Research Center. Thank you so much for being here Tia. 

Tia Higano: You're welcome Alicia.

Alicia Morgans: Of course. So we've talked multiple times. You know, I'm always intrigued by what you're working on and I know you've been doing some exciting data analysis in a Flatiron Registry and I'd love to hear what that project was and you know what your findings were?

Tia Higano: Sure. Well, the idea behind this was, as we all know, we've had all these new drugs in the metastatic CRPC setting. 

Alicia Morgans: Yes. 

Tia Higano: And just trying to get a handle on what people are doing out there. So the Flatiron Health Registry is a registry of, I don't know, I think 200 and something or other cancer clinics around the country. So this is all US based. So I should, you know, clarify that it's what we're talking about is this is treatment patterns within the United States. 

And most of the clinics are community-based. So that's another difference because certainly there are probably significant differences between what we might do in academia versus what everybody else is doing out there. And what we did in this was asked them to pull 4000 patients with metastatic prostate cancer, you know, randomly, and then to further pull out the patients with metastatic CRPC.

Alicia Morgans: Which they can do and Flatiron and as much more challenging in things like Sierra Medicare.

Tia Higano: Absolutely. Because I've been through that exercise too. 

Alicia Morgans: Yes, yes.

Tia Higano: So that resulted in about 2500 patients more or less with mCRPC. And so these patients were treated between 2013 and 2017. So that's the other thing to keep in mind, with, with some of the comments I might make and I'll try to remember to bring those up. But, so you know what we were looking at it again, is lines of therapy and what the sequences were and just treatment patterns. So the first part of the data was of the 2500 plus or minus patients, about 77% receive some form of life-prolonging therapy. So that's abi, enza, docetaxel, cabazitaxel, radium or sipuleucel-t.

But that means the remainder didn't get anything. I mean they did not get anything, but, so then about half of those 77% then went on to get a second line therapy.  And then half again of those went on to get a third line therapy. I guess in that particular time period a lot of people were doing this, but the most common first-line therapy was either abi and enza.  And the most common second line therapy was either abi or enza depending on what they had the first time.

Alicia Morgans: That's really interesting. So really sequencing the AR agents back to back. Rather than going on to a different mechanism of action.

Tia Higano: Yes. But it's also sort of, you know, well at least right now we all know that's something we probably wouldn't advocate, but you know, so I just want to go back to the dates. I mean, that was a different time. And I think a lot of us might've been doing that too.  And including combinations because that was part of it. And certainly, the preclinical trials going on at that time with the hopes that the two different mechanisms of action would result in a better outcome. But that wasn't really the case, we know that now. So, yeah, so that was, you know, interesting. The other sort of key finding, which is upsetting and that's, this is not related to the timeframe, is that only about 60% of the patients ever received either denosumab or zoledronic acid. 

Alicia Morgans: Wow. 

Tia Higano: Yeah. 

Alicia Morgans: At any time point, at any dose, not the up to monthly dosing, which is, you know, the indication? 

Tia Higano: Right. Yeah, I believe so. I'd have to double check that. But even still and now, because there are, and I'm sure you're well aware, there's many people who are using,  either one of these drugs in other than indicated dose schedule. 

Alicia Morgans: Yeah, of course. 

Tia Higano: So, I honestly, I can't remember if we looked at that particular question and that's a good question. I'll have to go back and look. But, you know, it's upsetting because we've had this kind of data for a long time that that recommendation's been in the NCCN for a long time. And I'm not saying that 100% of the patients should have been treated because certainly there are some, you know, where there's contraindications or whatnot or you know, financial reasons, but you know, the centers that are in this database, certainly are centers that must have practice pathways. 

And so it's kind of like, why, how could it be that high? But, you know, on the other hand, we know from, you know, Phase 3 trials that that's about the same thing.

Alicia Morgans: Yes. Except that this is metastatic CRPC and a lot of the recent Phase 3 trial data on these low utilization rates are really ... We've had some ...

Tia Higano: Oh yeah, and that's understandable. That's certainly understandable. But even ...

Alicia Morgans: But even in ERA 223.

Tia Higano: I was just going to say there, it was about the same. So that was another important finding. And then I think the third thing is when you really did the calculation, that only 20% of the patients were getting docetaxel as I said, so it's 

Alicia Morgans: In the entire treatment paradigm for mCRPC?

Tia Higano: Yeah. 

Alicia Morgans: 20% of patients? And that had been approved actually you said, what were the years? 

Tia Higano: 2013 through 17 ... Yes. 

Alicia Morgans: That was ...

Tia Higano: But I mean, I, so I'm the kind that hates to have a patient, you know, go to heaven without the benefit of having at least trying docetaxel. 

Alicia Morgans: Yes.

Tia Higano: And so, the fact that the majority didn't get any at all, it's now certainly this didn't follow all these patients out until death. So, but even still, it seems a very low number by the time, and this looked at, you know, first line, second line, third line not to have gotten docetaxel anywhere in there seems wrong. 

Alicia Morgans: Yeah, and that's really surprising. 

Tia Higano: Yeah. 

Alicia Morgans: Now it could be through part of that follow-up period. It could be some of those patients had just docetaxel per CHAARTED. Right.

Tia Higano: Well probably ... 

Alicia Morgans: In the metastatic hormone sensitive. 

Tia Higano: I don't think so because of the time period.

Alicia Morgans: You went through 2017?

Tia Higano: Well through September of 2017. Yeah. But I mean by the time they became castration-resistant, I doubt we would have been operating off the CHAARTED data yet.

Alicia Morgans: Yeah, you're right. I think you're right. I'm just trying to come up with why?

Tia Higano: Yeah. I know ...

Alicia Morgans: Because 20% is very low. 

Tia Higano: Yeah.

Alicia Morgans: And you also had, what was it, almost 20 something percent or 30% who never got treatment at all?

Tia Higano: Yes. At the beginning. Yes. Yes. They never got a first-line therapy or life-prolonging therapy. Maybe they got bicalutamide or something. I don't know. But...

Alicia Morgans: Yeah. But nothing that would be disease-directed. 

Tia Higano: Correct. 

Alicia Morgans: And proven to prolong life. 

Tia Higano: Exactly. 

Alicia Morgans: So these, I think these findings are really compelling, concerning because we have guidelines to help all of us as practitioners try to work through these problems. So what is your, what's your message? What do we do with this data and how do we take it moving forward as something to learn from and to move forward and do something positive? 

Tia Higano: Well, yeah, I think it's just going to be messaging. I mean we'll obviously publish a paper about it. 

Alicia Morgans: Yeah.

Tia Higano: And I think just increasing awareness that, hey guys, this is what we saw you are doing out there. 

Alicia Morgans: Yeah.

Tia Higano: And now the thing I mean, I'm curious to know but there's too few of them. If there is a big difference between academic centers and community centers.

Alicia Morgans: That's one thing. 

Tia Higano: But honestly, I'm not really sure because there's still like believers and nonbelievers out there. 

Alicia Morgans: I also wonder, and you'll have to let me know if you've already done this, have all of those patients been referred to medical oncology? So. if those patients’, providers are still only urologists, they're not going to get docetaxel.

Tia Higano: Yes. So I had that same hypothesis. However, I believe the Flatiron patients come from cancer centers, not urology offices.

Alicia Morgans: Well we should definitely confirm and get the provider of record.

Tia Higano: Yeah because I was asked that, and I, that was the first thing I said is that could be a reason. But then when I was thinking we're these, you know, the type of centers that are in Flatiron I think do not include just ...

Alicia Morgans: Urologists?

Tia Higano: Urologists. 

Alicia Morgans: Okay, well work to be done. Certainly working together with these patients in a multidisciplinary fashion or at least making sure that they have access or consideration to all of these life-prolonging therapies and certainly the supportive medicines.

Tia Higano: Right. Yeah, that's what bothers me that, you know, how could we, you know, now that we've seen the data from ERA 223, three and the fact that patients in that, which I think we've talked about before.

Alicia Morgans: Yes.

Tia Higano: You know, didn't have as many fractures when they had bone health agents as the ones who didn't. I mean, well we know of course. So this is what I want to say. We didn't know that data in 2017 obviously. 

Alicia Morgans: True. 

Tia Higano: But we know it now and moving forward, I think the addition of this data to that, those findings in ERA 223 hopefully should come together to help people feel more like a believer for those who were nonbelievers before. 

Alicia Morgans: Absolutely. Well, thank you so much for bringing more information to light. Sometimes reflecting back on ourselves is one of the most important steps to moving forward in a positive direction. 

Tia Higano: Absolutely. 

Alicia Morgans: And I really appreciate your interest in helping us do that as a community because if we don't look, we won't understand what's going on in the real world.





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