Roundtable Discussion: Landau Leads Debate on Treatment Decisions for Patients With Metastatic CRPC

Case-Based Roundtable Meetings Spotlight, Case-Based Roundtable Meetings Spotlight May 2021: Solid Tumors,

The case of a 75-year-old man with stage T2N0M0 prostate cancer was the topic of discussion between 8 oncologists, a physicians assistant, and a nurse practitioner during a recent Targeted Oncology Case-Based Roundtable event moderated by Daniel Landau, MD.

The case of a 75-year-old man with stage T2N0M0 prostate cancer was the topic of discussion between 8 oncologists, a physicians assistant, and a nurse practitioner during a recent Targeted Oncology Case-Based Roundtable event moderated by Daniel Landau, MD, of the Medical Oncology/Hematology Department at Orlando Health Cancer Institute.

LANDAU: I think we’ll get relatively universal agreement that this [patient] was somebody who was high risk and the approach of radiation is very appropriate, as well as ADT. I think the comment that’s being made is that maybe we could have been a bit more aggressive, given how high risk he was, and introduced earlier second oral ADT.

LANDAU: What about introducing the osteoclast-targeting therapy? Does anybody want to do that at this point? Do you want to wait? There were 2 small lesions present.

VISVALINGAM: If there is more metastasis, I usually start [therapy right away].

ORTEGA: Usually, once we have a patient on ADT and we have evidence of bone metastasis, we’re aggressive in starting bone-modifying agents pretty early. [This is] because of the combination of issues that are going to be added to this gentleman, [who] already has bone disease and he’s already going to be on ADT therapy. So, the answer would be yes, we would agree with early intervention.

LANDAU: [The patient] is going to be at risk of osteoporosis, because now he’s going to be committed to long-term ADT. He already has bony lesions, so it’s very reasonable to go ahead and start your drug choice or [his] insurance plan’s drug of choice.

LANDAU: It seems as if most of the slant is toward abiraterone [Zytiga] and enzalutamide [Xtandi], with a little bit of a docetaxel as well. Radium 223, I don’t think this would be the right situation for that. Most of us seem to feel that we would offer an oral second-generation drug. Does anybody else want to weigh in on their decision on why they picked what they did?

DANDAMUDI: Basically, this patient has an mCRPC with minimal disease, it’s not like an extensive disease, so that’s why I went with the abiraterone. If there is extensive disease, I would have started him on docetaxel first and then…abiraterone or enzalutamide later.

LANDAU: Very reasonable. Any major reason that abiraterone outweighed enzalutamide in the answer choices? Does anybody feel very strongly about one versus the other?

DANDAMUDI: In my experience with enzalutamide, patients have more fatigue and weakness. I had a bad experience with enzalutamide compared with abiraterone, so that’s why I try abiraterone before enzalutamide.

KASE: One thing…with docetaxel, even though [the patient] doesn’t have significant burden disease, no visceral metastases, [is] it could be considered more early on. [It’s 6 cycles] and he does have some pains. He may get more of a benefit up front.

Starting chemotherapy earlier…gives you more options down the road that you could start to introduce, because a lot of times these patients with mCRPC don’t end up seeing all the lines of treatment. So it may not be a bad idea to bring up chemotherapy a bit sooner, get the 6 cycles…done, and then you can watch them after that.

LANDAU: The sequencing is always going to be a hot topic of conversation. When I voted on this case, I voted for abiraterone, but my finger was not far away from clicking on docetaxel either. I tend to present all the options to the patient and have a detailed conversation about the pluses and minuses of the different drugs. I don’t necessarily feel strongly that we need to use an oral therapy versus chemotherapy, but that would be what I went to in this case.

LANDAU: My answer to this is probably to look at doing both [cabazitaxel] and [test for microsatellite instability (MSI) and DNA repair deficiency] because there can be a delay in getting some of those…results.

LANDAU: Does anybody want to weigh in on their decision-making and why they picked what they did?

ORTEGA: My issue is on the sequencing about how we’re doing things. I would have probably checked MSI and DNA early in the sequence of everything. I think that at this point, with the volume of disease and aggressiveness of disease, that not only getting the testing results back but then trying to get authorization of all these things probably would put us a couple of months behind.

I’d be inclined to start with cabazitaxel first, just because of those issues. If I [had] ordered the test before and I [had] had it available, then I would probably be visiting that other option early.

LANDAU: When are you sending these patients for testing?

ORTEGA: As early as I can.

NAKKA: Because the patient already developed some neuropathy from the previous taxane chemotherapy, I’m hesitant to consider cabazitaxel right away. I usually start sending MSI [for tests] right around the time when I see that the PSA is starting to go up, so I prepare for the other options. Also, [regarding] the gene assay to check BRCA and other mutations, I would send that as well.

LANDAU: In our practice, whenever we see these gentlemen who are high risk off the bat with these very high Gleason scores or very high PSAs, I’m sending them to our genetic counselor immediately, often before they even have their local therapy. I agree with what we’re saying that it’s better to get this testing early so we’re not scrambling later on. You also mentioned the neuropathy. He did have neuropathy before, so the docetaxel was stopped early. It can be manageable. You can still offer these patients cabazitaxel, but you have to keep that in the back of your mind, that it may become a problem yet again.

KASE: Yes, I would definitely agree, especially with DNA repair deficiencies, and especially [seeing] he’s already received a taxane therapy. If he does have a BRCA mutation, [patients] generally respond better after receiving taxane. I think it’s niraparib [(Zejula) that’s] approved after taxane, while olaparib [Lynparza] you can use after abiraterone. But I think those patients did better after getting a taxane in general. All of this should have been more up front in the metastatic setting to prepare down the road.

COLEMAN: We test early for the assay to see if they have any mutations and [what] targeted therapy [will fit].

PARAS: I did choose abiraterone and prednisone for the same concept. Back-to-back chemotherapy would be sometimes harsh on a patient. With neuropathy, I’ll probably try a different mechanism of action. In this case, for the back pain, well, you can put them on abiraterone and probably [expect] symptomatic bone metastases.

Around that time I would also test for MSI and for BRCA mutation, I think it’s just a matter of sequencing. The way I see those patients, all of them would probably get this medication. It’s just a part of my sequencing, what their symptoms are and how their body can tolerate the treatment at the time.

LANDAU: We talked about the different treatment options. There have been a number of comments about his prior neuropathy. How much does age play a role to everybody when you’re picking your [treatment]?

DANDAMUDI: I would say quite a bit, depending on his performance status.

LANDAU: I always talk about biological age more than chronological age, which I think is where the performance status comes in.

TAN: In my patient population a lot of them are in their 60s and I consider comorbidities, especially in patients who have diabetes and prior neuropathy. Some of them have liver disease and things like that. In those types of patients, I would probably avoid abiraterone for those with liver disease and those with significant comorbidities, including diabetes.

Prednisone can also be difficult to give. Sometimes with chemotherapy, although it’s not written, but in the early hormone-sensitive phase, we do give docetaxel without the prednisone. Sometimes in the setting of other chemotherapies I try to drop down the prednisone, especially if the prednisone causes morbidity later.

LANDAU: I agree with you completely. If someone’s been switching from abiraterone to docetaxel, I’ll keep the prednisone on it because they were already on it, they were already used to it. But in general, I try to get rid of it as quickly as I can.

TAN: I have seen several people, although we give them very low doses of prednisone of about 10 mg a day, [who] do develop adrenal insufficiency. So I think we should make sure that we taper them off, especially because of their age and other comorbidities. We can see some signs of adrenal insufficiency in those patients.

LANDAU: Absolutely. A comment came up earlier about somebody who was on prior enzalutamide going on to abiraterone. I’ve not really been in the practice of switching from one to the other, outside of very specific situations. But to the group, I’m curious how often you do that and how often you’ve seen a benefit from doing this?

DOSHI: When the drugs [were] new in the market, we were doing it; but as we used it, we realized those second responses were very minimal or very short-lived so usually we switch.

LANDAU: I agree. I look at it as a shared mechanism of resistance between them. There are times that I have done it. I think a lot of us have seen that 1 patient or those few patients where it has worked. But as a whole, it’s not my preference, particularly in the patient who is becoming progressively symptomatic.

There was also a comment earlier about somebody who had issues with docetaxel, using cabazitaxel post docetaxel. I’ve done it, but I’ve been very cognizant of what the issues were with docetaxel before. So very early and aggressive monitoring of the neuropathy [is required, and] maybe the introduction of a Neurontin [gabapentin] or another agent to help offset it.

But I have wanted to offer cabazitaxel based on the survival benefit. Even with prior docetaxel issues, I have still offered cabazitaxel after it. Does anybody feel very differently?

ORTEGA: I just want to make another comment here, because this option has not been offered and it just came out of some recent data. [It concerns when] we’re adding apalutamide [Erleada] to abiraterone plus steroids, which tells us that maybe while they may not substitute for each other, there may be the possibility of some synergistic activity by them working at different sites.

In the future we might start looking at this slightly differently, given that study. If it’s true that by combining them we may get a long period of remission, this discussion may become mute in the future because they may have been on both [treatments] at the same time.

LANDAU: We participated in a study where we combined abiraterone and enzalutamide, but there was too much hepatic toxicity so that one had to stop. But there was excitement there and there’s still excitement now about where this may be heading.

LANDAU: I mentioned before about the early use of drugs like Neurontin to help with neuropathy issues. I also think one of the big changes with cabazitaxel, in terms of the toxicities, was that recently the recommended starting dose was lowered. That helped with my practice in managing some of the toxicities.

LANDAU: What do you think about cabazitaxel? Much experience? Have you seen a lot of adverse events?

ROCHE: We have 2 patients on it right now. One [just started and another] patient, a younger guy, is doing well. We’ve had a couple of patients on it in the past as well. I think considering COVID-19 and everything [that] sometimes it’s the patient who’s afraid to go on the intravenous treatment rather than the oral, because they want to stay home.

In addition to that, a lot of times—I don’t know about other practices—we have found that the urology [department] sees these patients for a long time, and we don’t get them until every oral agent is out the door.

LANDAU: Good point.