Ep. 11: Factors in Selecting Therapy for mCRPC

Transcript:

Neal Shore, MD, FACS: Does anybody on the panel want to talk about their own experience in terms of how these patients are presenting in your clinic?

Alicia K. Morgans, MD, MPH: In my clinic, there are definitely more patients who have de novo metastatic disease, which has implications if we’re choosing therapy in the metastatic CSPC [castration-sensitive prostate cancer] setting. I don’t know if we really addressed it in our CSPC conversation, but de novo metastatic disease may be a population of patients who receive benefit from up-front chemotherapy. Not necessarily more so than AR [androgen receptor]—directed therapies, but they receive more benefit than patients who have recurrent metastases after localized therapy. That’s something I’m seeing more of because of changes in PSA [prostate-sensitive antigen] screening.

That is going to have downstream effects in the metastatic CRPC [castration-resistant prostate cancer] setting. If I used chemotherapy in the up-front setting, then I certainly can use cabazitaxel in the metastatic CRPC setting, but I also have the option of using 1 of the androgen receptor—directed therapies. We all do this. As we’re thinking about choosing therapies in the metastatic CRPC setting, we’re always thinking back, “What did they receive before?” Whether it’s in the nonmetastatic CRPC setting, the metastatic hormone-sensitive setting, or the metastatic CSPC setting, I always think about changing mechanism of action.

That’s what we need to do and what we find is most effective: not necessarily chemotherapy to chemotherapy but particularly with the AR-directed therapies. We’re fortunate to have multiple approaches available to us. I’m not sure what all of you think, but changing mechanism of action and not sequencing AR therapy after AR therapy is a key tenet to the way I think through things and the way I talk to patients. It’s something I try to avoid.

Neal Shore, MD, FACS: That’s a really good point, and the data that I’ve seen show that there’s a lot of AR-AR sequencing that happens, and possibly it’s going on for a whole host of reasons. It may just seem that it’s convenient. It’s exchanging 1 oral therapy for another oral therapy. We’re going to talk more about that. But let’s get into the granularity of it. Pedro, you have a patient who comes in, and they’ve been treated with ADT [androgen deprivation therapy] and 6 cycles of docetaxel for hormone-sensitive, metastatic, high-volume disease that had spread to the bone and soft tissue. Now they present to your clinic with mCRPC. What goes through your thought process in offering additional therapy?

Pedro C. Barata, MD, MSc: It’s a loaded question, so thank you for that. I would test for genomic information, which we can discuss.

Neal Shore, MD, FACS: That’s great. What would you test for?

Pedro C. Barata, MD, MSc: Up front, I try to be ahead of the game. Knowing what we have as far as standard of care, but also what else I do that’s outside the box. As a side note on the genetic information, all patients with advanced prostate cancer should get germline testing, right? It’s now in the guidelines, and the reason for that would be not only because we can impact therapeutic implications for these patients, which we’ll get to in a second, but also because it impacts how we find families at risk for hereditary syndromes. It can address that and have a huge impact on the family, for prostate cancer or other cancers. We can do that. The sooner we do it the better, because we have time and don’t need to rush to find their parents or siblings or children, right? That’s 1 part of the story, the germline status.

For the patient who is in front of me, the question is about some great, emerging targets for therapies out there. I’m obviously thinking about the homologous recombination repair deficiencies. I’m thinking about microsatellite instability. A little less prevalent, but also relevant, are the PTEN and PI3K-AKT pathways. Those are factors that are relevant for us to know. We’ll talk a little about the therapeutic implications of those targets.

On top of the germline testing, I also think about somatic testing, whether it’s in the tumor, tumor tissue, or circulating tumor DNA. The caveats of tumor tissue are that oftentimes in prostate cancer, as William Oh referred to, 90% of patients will have disease in the bone, about 50% will have disease in the nodes, and about 20% will have visceral disease.

It is a problem for us, in terms of performing biopsies, to get access to tissue in the context of metastatic disease. There’s archival tissue that is there from a radical prostatectomy, but it happened 4, 5, or even 10 years ago, right? A lot of us are using or pushing for circulating tumor DNA assays and NGS [next-generation sequencing] assays on circulating tumor DNA, because we don’t have access to tissue the same way we do for other cancers. That somatic information provides more value than having only germline information.

Transcript Edited for Clarity