Cabazitaxel as a Third-Line Treatment After Docetaxel and an Androgen Receptor Targeting Agent in mCRPC Patients – Alicia Morgans

December 27, 2021

Alicia Morgans joins Oliver Sartor in this UroToday conversation highlighting a modeling analysis of cabazitaxel compared to repeat treatment with an androgen receptor targeting agent (ARTA) among patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and the alternative ARTA. This analysis uses a hypothetical cohort of patients who are similar to the CARD patient population and looks at the health economic implications of using cabazitaxel in that third line mCRPC space, as compared to sequencing another AR targeted agent. In the CARD trial, cabazitaxel was shown to significantly improve clinical outcomes compared to a second course of treatment with ARTA in mCRPC patients who previously received docetaxel and the alternative ARTA.

Biographies:

Oliver Sartor, MD, CE and Bernadine Laborde Professor of Cancer Research, Medical Director of the Tulane Cancer Center, Assistant Dean for Oncology Tulane University School of Medicine

Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts


Read the Full Video Transcript

Oliver Sartor: Hi, I'm Dr. Oliver Sartor, medical oncology at Tulane University, and Medical Director of the Cancer Center down in Tulane. And really a pleasure for me to introduce someone who needs no introduction, and that is Alicia Morgans, and Alicia is GU Medical Oncology at Dana–Farber. And welcome, Alicia.

Alicia Morgans: Thank you so much, Oliver. It's truly a pleasure to be here with you.

Oliver Sartor: A pleasure for me as well. We're going to discuss a presentation that you gave at ESMO very recently, and it was interesting. It involves the CARD trial. I want to, first of all, hear a little bit about what motivated you to do this study, and then a little bit about the findings, of course. But let's start out with, what motivated you to get focused on this particular issue?

Alicia Morgans: Sure. I really appreciate that question, because I think a lot of what we do as oncologists, is helping our patients make choices that make sense for them, both in terms of disease control, but then also, having to make sense from a practical standpoint. Part of practicality for patients, and for clinicians, of course, is health economics. And really, that transfer of data from efficiency in a clinical trial, to effectiveness in our clinical practices, does require some understanding of what are the implications, in terms of, who's going to pay for this? How do we actually deliver this treatment to our patients in a way that helps them have access to the treatment that they need?

So this analysis is really, using a hypothetical cohort of patients who are similar to the CARD patients, and we can go through what that kind of patient is at some point, but really, it's to understand in this cohort, what are the health economic implications of using cabazitaxel in that third line mCRPC space, as compared to sequencing another AR targeted agent.

Oliver Sartor: Good. Can we back up just for a second? Because I think most people may be familiar with the CARD type population, but can you cover that a little bit, just to give us that background?

Alicia Morgans: Sure. CARD was really a phase four clinical trial, that was looking at patients who had metastatic castration-resistant prostate cancer, who had already received treatment with docetaxel and an AR targeted agent, either abiraterone or enzalutamide, though they had to have received that drug for 12 months or less and have had progression of disease with both of those treatment approaches. And in the CARD trial, patients were randomized to receive cabazitaxel at 25 milligrams per meter squared, or that alternate AR targeted agent. And really, they had a radiographic progression-free survival primary endpoint, and secondary endpoints included complications, like SSEs, as well as overall survival. So it was really to try to understand whether cabazitaxel would be a good option for the next line of therapy, as compared to that second AR targeted agent.

Oliver Sartor: Right. And I'll just comment a little bit. I thought the CARD trial was very important because it was the first, really third-line trial. Everybody had docetaxel, everybody had an AR targeted agent, and now the question was, what comes next? So overall survival, positive, most people know that. But let's go into your analysis in a little more detail. Tell me, Alicia, about what you found in this study.

Alicia Morgans: Sure. We tried to look at all of the complications that patients may experience when they are getting treatment for their cancer, as well as the benefits. Things like progression-free survival that is prolonged, and overall survival that's prolonged. And there are ways, in health economic analyses, to transfer those benefits and those complications into real dollars. And so that is what was done with a health economics team, that is really skilled in that. And Dr. Nick Vogelzang and I gave our impressions of what hospitalization times would look like, and what those complications would be, in terms of time lost for patients, particularly. The rates of these events were taken from the CARD data, so that was coming from real data. And all of these things were quantified, in terms of 2020 US dollars. So they put a dollar amount on them. And then as we looked at the rates, and then looked at the dollars, we were able to convert that into health resource utilization.

So in a cohort of about 100 patients who were analyzed 18 months after hypothetically starting a CARD regimen, either cabazitaxel or that alternate AR targeted agent, we found that about nine patients had that prolonged radiographic progression-free survival, who would not if they had a second AR targeted agent if they were then treated with cabazitaxel. Two patients had progression-free survival when treated with cabazitaxel, as compared to that second AR targeted agent, and 17 people were alive when treated with cabazitaxel, versus the second AR targeted agent.

To dig into hospitalizations and skeletal-related events, we found that there were 58 fewer hospitalization days for patients treated with cabazitaxel, and two fewer ICU days with cabazitaxel, then again, the second AR targeted agent.

Oliver Sartor: That's really interesting. I think people typically associate chemotherapy with more toxicity, more hospitalizations, we actually found the opposite. Let me just ask you, what about hospitalizations that may have occurred from febrile neutropenia, or that sort of complication? I'm sure that entered into the equation.

Alicia Morgans: Absolutely. So that's what was included. We looked at all of the AEs, essentially, in the CARD data, and then converted each of the ones that would actually cause hospitalization, into percent of hospitalization, and febrile neutropenia, that's all going to include hospitalized patients. And then, that is how they looked at how those rates would actually translate from an AE chart in a paper, into these kinds of outcomes, like hospitalizations and ICU days.

So essentially, where Dr. Vogelzang's knowledge and mine came in, is that we would say, well, what percentage of patients with febrile neutropenia are actually hospitalized? That would be 100%, at least in my practice. What percentage of those patients then have higher grade complications that they need ICU stays? And so that was estimated. Things like hypercalcemia, what percentage of patients are treated as an outpatient, versus what percentage of patients are treated as inpatient? So there was actually a fair amount of literature review. We couldn't just come up with these numbers with our own gestalts. We had to go back and say, well, here are some papers where these complications were managed, and this percent, essentially, goes in the hospital, this out. And that's where, hopefully, some of the thought came into this analysis.

Oliver Sartor: Good. Quick question about G-CSF. Was G-CSF an assumption? Was G-CSF utilized with the cabazitaxel?

Alicia Morgans: It was utilized in the same way in our hypothetical cohort, as it was done in cabazitaxel. So I would say, G-CSF administration in itself, was not actually analyzed in the model, because it was the rate of febrile neutropenia, sort of the downstream effect of use, or not use.  Or even if you use, you may still get febrile neutropenia, but it was a downstream adverse event that was really categorized and included in this analysis, rather than the use of the agent itself.

Oliver Sartor: Great. Well, that is a really nice synopsis. Now the conclusion that I would draw, is that chemotherapy in these third-line patients turned out to be advantageous. Not only from the RPFS and the OS, which has been previously reported but also from the health economic perspective. I think those are important findings.

Alicia Morgans: I appreciate that, and I agree. We really found I did mention, but we also found a 21% reduction in SSE events, as well as in end-of-life care costs. So the actual cost, when we translated to dollars, went down, and a 17% reduction in overall healthcare resource utilization reduction. So I think, from a patient perspective, as I said again, in terms of practicality, as well as from a disease controls perspective, I think that this is helpful to demonstrate that both are actually winning, when we change our mechanism of action and use cabazitaxel in this space.

Oliver Sartor: Right, Okay. I'm going to ask you to keep the response to the next one short, but it's going to be a really hard question. There has been the TheraP trial, done by the Australians, comparing the PSMA-Lutetium 617 and the cabazitaxel, and then the VISION trial, which is also kind of a third, or fourth, or fifth line trial. And I wonder if you might give any inclination about how you might view the isotopes in this context?

Alicia Morgans: I think it's a great question. But to your point, I think it's really challenging to answer. In my practice, I hope that patients will have access to all available therapies, and until we see data that the use of one drug really precludes the use of another drug, I think we are going to want to try to use everything that we can to help these patients improve quality of life and maintain the length of their lives.

So I guess the short answer is, TheraP suggests that we could really kind of maybe choose cabazitaxel, versus Lu-PSMA-617, and how do we make that choice? Well, I think from a clinical perspective, we can look at that it's only a phase two study, of course, but we can look and try to make that choice with our patients. It will take a whole other analysis to include, of course, the cost of complications, the cost of the drug, for both of those approaches, to really understand whether it makes sense from a healthcare resource utilization perspective, but that's not always the decision-maker. Sometimes it's patient preferences, and sometimes just quality of life. Sometimes it's the ease of receipt of therapy. So each patient will still need to make that choice himself. But if that analysis is done in TheraP, we will have, at least, more information to inform that decision.

Oliver Sartor: Right. That is a great answer. Alicia, really a pleasure to be able to chat today, and we really appreciate your contributions to ESMO, and we look forward to your new career at Dana–Farber.

Alicia Morgans: Well, thank you so much. It is always a pleasure to talk to you.
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