Around the Practice: Improving Outcomes in Advanced Prostate Cancer - Episode 5

Patient Case #2: Choosing Optimal Therapy in mCRPC

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Raoul S. Concepcion, MD, presents the case of a 64-year-old-man with mCRPC, and Jason M. Hafron, MD, CMO, leads the discussion on the optimal treatment approach for the given case.

Raoul S. Concepcion, MD, FACS: Let’s switch gears. Now we’re going to move into module 2, which is choosing an optimal therapy for patients with metastatic castration-resistant prostate cancer [mCRPC]. In this case, we have a 64-year-old man who was being treated for metastatic prostate cancer with lower abdominal pain, constipation, lower urinary tract symptoms. His PSA [prostate-specific antigen] was 30.2 ng/mL. His initial biopsy showed Gleason group 5 (5+5), all cores positive. He had 2 metastatic bone lesions in the pelvis, but no nodal involvement. His ECOG performance status was 1. For comorbidities, he was a diabetic. Let’s just summarize this. This is a patient who presented with high-grade disease, underwent radical prostatectomy, got started on ADT [androgen deprivation therapy]. Initial work-up was negative. He had ADT plus bicalutamide because he never hit nadir and then rapidly progressed to having recurrent disease with 2 metastatic bone lesions in the pelvis. By definition, he has metastatic castration-resistant prostate cancer and presents for initial therapy.

In this case, he’s treatment-naive, but he is metastatic and he’s castration-resistant. The choices are docetaxel plus ADT, ABI [abiraterone] plus ADT, Enza [enzalutamide] plus ADT, or other? Let’s let the audience vote. Jason, I’ll start with you again. This is the patient we used to see 10 years ago. I don’t think we’re seeing them much now because we’re treating so many patients early and in the nonmetastatic space, but this was a guy who would have presented. What are your thoughts relative to this guy? High-grade disease, really blew through ADT quickly and became metastatic.

Jason M. Hafron, MD, CMO: First of all, if germline hasn’t been tested, I would get my germline testing. I like to get somatic testing up front; it is probably not going to make a difference at this point, but I like to understand the pathology of his disease. Vitamin D, calcium, get him on these bone resorptive agents because there’s more and more literature saying that’s important to get that started right away. Then in our center, we mostly start with sipuleucel-T [Sip-T]. For early mCRPC, we like to start with Sip-T and then typically transition to one of the oral treatments. Then the choice of the orals is what we’ve already discussed. Fitness for an ARI [alpha-reductase inhibitor], fitness for [abiraterone], and talk to them about chemotherapy, their fitness, can they tolerate chemotherapy? The key is having that discussion with the patient, the shared decision-making model, understanding what their goals are, looking them over from head to toe and seeing what the best treatment regimen is, but it would probably be Sip-T plus an oral in our institution.

Raoul S. Concepcion, MD, FACS: Dan, if you will, he was germline negative. What are your thoughts about somatic testing early in somebody like this who’s never seen a line of therapy? I guess the question is how early are we now moving up genomic testing for these patients?

Daniel P. Petrylak, MD: Certainly, I think the yield is going to be pretty low. Usually, I like doing somatic testing when I have a change in condition. If they’ve gotten visceral disease, or this patient is accelerating fairly rapidly, so it’s possible you’re going to see something. But I would probably at the beginning, at castration-resistance is the time I would check for it. May I make comments about treatment?

Raoul S. Concepcion, MD, FACS: Yes.

Daniel P. Petrylak, MD: This is a dilemma because he is sort of out of the category where we would use Sip-T. What I mean by that is the absolute PSA value. I like to use Sip-T early if the PSA is less than 22 ng/mL, which is an indirect measure of the volume of disease. The patient does have 2 lesions on bone scan, so he’s got a really low volume disease, but rapidly progressive. If you’re going to give Sip-T, I would consider giving it in this situation prior to chemotherapy or second-generation hormones.

Raoul S. Concepcion, MD, FACS: Oliver?

Oliver Sartor, MD: I’m similar to Dan on this one. It’s a little borderline for Sip-T because of the aggressive nature of the progression. He really didn’t get a lot of the hormones. The people who have a tendency to do a little better on the Sip-T are those who have a little more indolent disease. At the time of the Sip-T studies going all the way back, this was published in 2010. It’s 11 years ago, it didn’t have access to the novel hormones, so there’s a question about how much do we add on the Sip T front when you have the novel hormones? That’s an unanswerable question. I just raise it, but I don’t mean to give an answer because I don’t know. In terms of the testing, it’s reasonable to consider the somatic, and you can either do it now or do it later. I sometimes find that if the biopsies are done elsewhere that you can shuffle around for a month or so before you even get some tissue to do the somatic testing. If I know I’m going to need it, and I know I’m going to need it in this patient, I might go ahead and try to get the somatic testing relatively early, even though I don’t know what to do with it at the time I get the results back because I’m probably going to use a secondary hormone.

Now, the one thing I’m going to raise, and this gets into a future category that is very undefined, the PROpel study, which is a combination of abiraterone and olaparib, has reported by a press release that it is “positive.” I don’t know what that means. I don’t know if positive means slam dunk positive. It’s positive in the eyes of the manufacturer, which may not be the positive that I want to see, but it raises this new question about PARP inhibitors coming up front. There’s another study called the TALAPRO-2 looking at enzalutamide in combination with talazoparib. We don’t know anything about that, but I would simply say that if PROpel is positive, then maybe the TALAPRO-2 is going to be positive too. Even though today, we’re kind of walked into probably considering these novel hormones, it could be that combination therapies may play in the near future. I think we’ll hear about it at ASCO GU [American Society of Clinical Oncology Genitourinary Cancers Symposium], but we just have to learn more. Anyway, I just wanted to raise the PROpel study and mention it.

Daniel P. Petrylak, MD: With the PROpel study, the devil is in the details. I’m excited that it showed a positive result. However, we’ll draw on our experience at Yale School of Medicine; Joe Kim, MD, who works in our group, did a randomized trial of olaparib plus or minus cediranib, used potentially to increase BRCA-ness by causing hypoxia, randomized phase 2. Our primary end point in selected patients was rPFS [radiographic progression-free survival], very similar to the other trial. What we found when we analyzed the molecular data was rPFS was being driven by BRCA1/BRCA2 patients. It may be that the combination prolongs PFS [progression-free survival] or OS [overall survival] in that subgroup. The subgroups would be crucial in this trial to understanding how to use this combination.

Raoul S. Concepcion, MD, FACS: Ultimately, I would have loved to have seen another arm, which would have been PARP only. They had [abiraterone], they had [abiraterone] plus the PARP, but they didn’t have the PARP only. And to your point, Dan, at the end of the day, is all this going to be driven by BRCA2? Who knows?

Transcript Edited for Clarity