Prostate Cancer: Evolving Treatment Approaches - Episode 5
Neal Shore, MD, FACS: Pedro, can you summarize some of the other really fascinating studies and trials that are ongoing in mCSPC [metastatic castration-sensitive prostate cancer] that you or anybody else is a part of?
Pedro C. Barata, MD, MSc: Absolutely. Actually, it’s great because this space is getting so much more crowded, and we know it’s going to become even more crowded. I can quote 2 or 3 studies. One is exploring darolutamide, which is another novel AR [androgen receptor]—directed therapy, on top of ADT [androgen deprivation therapy] and chemotherapy, which is a standard of care. That one is called the ARASENS study. The other study is asking a little bit of a different question and is called PEACE1. It’s basically adding abiraterone to docetaxel, plus or minus radiation to the primary tumor. That addresses the role of addressing the primary tumor in the context of metastatic disease. We have other trials.
We are exploring triplet therapy, for instance, with chemotherapy—carboplatin and cabazitaxel—on top of abiraterone, called CASCARA, which is an academically led trial. We are seeing PSMA [prostate-specific membrane antigen] therapeutics, which we’re going to talk about later today. Moving into the hormone-sensitive space, we have a large phase III trial that is already approved via the cooperative groups and NCI [National Cancer Institute]. That’s going to launch relatively soon. These are exciting times, and we’re going to have more good solutions in the near future.
Neal Shore, MD, FACS: And molecular profiling too. We’re doing a couple of studies with PTEN loss, looking at PIK3/AKT druggable targets. Is there anything exciting for you all in the mCSPC space, William?
William Oh, MD: Just as in the mCRPC [metastatic castration-resistant prostate cancer] setting, in this metastatic hormone-sensitive setting, the question is with sequencing and combinations. We’re going to get some prospective data, but just as a reminder, when ENZAMET was presented at ASCO [American Society of Clinical Oncology Annual Meeting], 1 of the reasons it became a plenary talk was that about 40% or so of the patients actually got chemotherapy and were randomized to enzalutamide. There was a chance to look at the 40% of patients who got chemotherapy versus the 60% who didn’t. Basically, in the group that got chemotherapy, there didn’t seem to be an additive benefit to using enzalutamide. That’s not proof, but it seemed to suggest that combining these treatments, at least in this early attempt, is not necessarily beneficial. We really shouldn’t be doing that outside a clinical trial. Some of the trials that Pedro just mentioned will get us to that point regarding whether we should be giving chemotherapy plus an AR-targeted therapy to these patients with hormone-sensitive prostate cancer.
Neal Shore, MD, FACS: That’s a great point. It’s always been the bane of the development of the taxanes. They’ve really had a hard time finding couplet therapy benefit, but hopefully we’ll see that at some point.
Nancy Ann Dawson, MD: I was just going to make 1 other comment about the ENZAMET trial. The ENZAMET trial at the moment shows us that you don’t want to put those therapies together. But with the ARCHES trial, patients were allowed to have up to 6 cycles of docetaxel before they got enzalutamide. That trial actually showed benefit whether you had received previous docetaxel or not. Those patients actually had an improved outcome, and 1 of the things we forget about when we’re thinking about sequencing is that there are data that support that. Let’s say you chose to give a patient docetaxel for 6 cycles. There are data that actually would support that adding a drug like enzalutamide after that might be beneficial to them as well. It’s not administered at the same time.
Alicia K. Morgans, MD, MPH: I think the subset of patients in that trial—and when we think about TITAN too—was only 10% of patients or so who had had the combination of all 3 agents. I absolutely agree that this information will be coming, but at this point I don’t use all 3 agents, certainly not concurrently because of the ENZAMET toxicity data. But the added benefit in the setting of financial toxicity and potentially adverse effects, we just don’t know. It’s something that we’ll see with PEACE1, as well as with other studies I definitely look forward to seeing soon.
Neal Shore, MD, FACS: That’s a great point. You’re right: there was a small subset in TITAN and in ARCHES where we saw some benefit. It wasn’t predefined, and you had to look at the forest plots. It’s an interesting point. Patients may sometimes want to say, “Hey, you gave me my 6 cycles of docetaxel and my PSA [prostate-specific antigen] is still nadiring. What else can I take?”
Nancy Ann Dawson, MD: As you said, a patient I just saw had gotten 6 cycles of docetaxel and his PSA had dropped but was now plateauing. He still had lots of bone metastases. And he said, “Is there anything else you should add?”
Transcript Edited for Clarity