Management of Advanced Prostate Cancer in Urology: Update on Androgen Receptor Inhibitors - Episode 7

Approaching Treatment of mCSPC

, , ,

Vivek K. Narayan, MD, MS, shares thoughts on approaching treatment selection of mCSPC and Ashley E. Ross, MD, PhD, comments on the use of relugolix in patients.

Neal Shore, MD, FACS:Vivek, now we have level 1 evidence. It’s in the NCCN [National Comprehensive Cancer Network] Guidelines, AUA [American Urological Association], ESMO [European Society for Medical Oncology], ASCO [American Society of Clinical Oncology], EAU [European Association of Urology]—it’s out there. How are you educating the folks at Penn [University of Pennsylvania Perelman School of Medicine]—fellows, residents, urologists, oncologists? Our colleagues who are listening, how do you make a decision? What’s going on when you’re knee to knee in the clinic with a patient or a family member? How do you differentiate an issue around safety and adverse-effect profiles as well as monitoring?

Vivek K. Narayan, MD, MS: In terms of selection of what additional therapy to add? The way I try to frame the discussion with patients with de novo high-burden metastatic disease is that we have a wealth of potential options. The most important point, as we alluded to earlier, is that something needs to be added to the underlying ADT [androgen deprivation therapy]. There’s a lot of nuance about which therapy to add, but what we can easily say is that to improve long-term outcomes, we need to use some initial combination approach.

The decision about up-front taxane chemotherapy vs an AR [androgen receptor] signaling inhibitor is obviously much more difficult or personal. I remain a high utilizer of initial chemotherapy in patients, especially with de novo high-burden metastatic disease. My rationale there, and the discussion I have with the patient, is it’s not often, “Which option are we going to choose?” but rather, “Which are we going to use first as your initial treatment for metastatic prostate cancer?” Especially considering the PEACE-1 data and with some of the other emerging data that are going to come out over the coming year, there can be a potential role, now with higher level 1 evidence, for potentially early incorporation of chemotherapy and potentially AR-directed therapy as well.

Neal Shore, MD, FACS: I appreciate that. Ash, let me ask you. You and I have had some debates, and I’ve learned that I’ll never accept debating Ash again because he’s just impossible. He kills me. One of the questions you and I have debated upon the role for this new oral GNRH antagonist, relugolix. Where does a drug like relugolix, fit into the mCSPC [metastatic castration-sensitive prostate cancer] treatment regimen when you’re talking to your residents and fellows?

Ashley E. Ross, MD, PhD: I was excited to see it approved for a few reasons. The most exciting characteristic of relugolix is in the defined therapeutic space. In other words, if you have someone who’s going to get hormone therapy with their radiation, I find I’m reaching for it the most in men with this defined window of 6 or 18 months, particularly younger guys who want to have their testosterone recover very quickly after the therapy is over. Sometimes, I’m also using it in my older gentlemen, where I don’t know how they’ll tolerate the effects of ADT or if they have some cardiovascular adverse effects.

In guys who have mCSPC and are going to be on lifelong hormonal androgen deprivation therapy, I don’t know if that’s the wheelhouse for relugolix. I still reach for it as my initial therapy for people with cardiovascular morbidity. There are some mixed data around that, but there’s a cost component to it. There’s a drug-drug interaction component. If I’m going to have someone on lifelong ADT because they have CSPC [castration-sensitive prostate cancer], I usually don’t reach for it.

There’s 1 unique state that might be too nuanced for this discussion. That’s PET [positron emission tomography] PSMA [prostate-specific membrane antigen]. You’re finding guys with oligometastatic disease, particularly in the case of oligometastatic disease after definitive treatment to the pelvis. They’ve had a prostatectomy. They’ve had radiation. Their PSA [prostate-specific antigen] is rising again, and they have a BCR [biochemical recurrence]. You scan them. On PET imaging, you see 3 spots. That’s another place where I think about a definitive window of androgen deprivation therapy, and I’m not sure if I’m going to use a combination systemic intensification in that window. I’m certainly not going to use a triple therapy like PEACE-1. In that setting, where I might do 6 months of ADT again as I ask my radiation oncologist to “spot weld”metastases, it’s another great wheelhouse for relugolix. That’s really nuanced, and I’m sorry to even have gone there. But there’s power to relugolix. A lot of it is that quick-recovery testosterone, which isn’t what we’re looking for in the guy who has fulminant metastatic CSPC.

Neal Shore, MD, FACS: These are all great points—a great discussion and a review of so much—it’s the proverbial embarrassment of riches in mCSPC, and there are many better things to offer our patients. Clearly, combination therapy is the standard of care, bar none, hands down. We all agree with that. And we have the luxury of 4 AR pathway drugs, 2 specific androgen receptor pathway inhibitors. Abiraterone is an androgen biosynthesis inhibitor, or a ligand inhibitor, and docetaxel is in the form of a taxane.

Transcript Edited for Clarity