Alicia Morgans: Hi, my name is Alicia Morgans, and I'm a GU Medical Oncologist and Associate Professor of Medicine at Northwestern University in Chicago in the US. I'm so excited to have here with me today, a friend and colleague, Dr. Ashley Ross, who is an Associate Professor of Urology, also at Northwestern here in the US. I've asked Dr. Ross to talk with me a little bit about how he thinks about patient selection, conversations with patients, and operationalizing oral GnRH antagonist use in his clinical practice. Thank you so much for being here with me, Dr. Ross.

Ashley Ross: Thanks for having me.

Alicia Morgans: Wonderful. So, Ash, let's start with that first question. How do you actually think about choosing patients, either new patients or patients who have been on longer-term ADT who might be good candidates, for use of a GnRH antagonist that's an oral agent?

Ashley Ross: Yeah, so it's a great question. As the audience and as you well know, relugolix was recently approved for advanced prostate cancer, and the data, showed us a bunch of things. One, that it certainly can cause castration, it certainly can lower the testosterone to fairly significantly low levels, maybe lower than some of the injectable agents, and additionally, there seemed to be at least a signal for a decreased amount of major cardiovascular events.

And so, when I'm thinking about starting a new agent or a new androgen deprivation therapy regimen for an individual, I first think about their cardiovascular risk. For the patients, I see that have a history of major cardiovascular events, or even things that are pretty significant in their history for risk factors, those are who I push for the new agent and tell them, "Look, this exists. You're a patient that I used to think about for degarelix." For degarelix, in my hands at least, I sometimes would get skin reactions that were bothersome, but I tell them that, "It's an easier way to take the drug as an oral pill, and it's now available. We should strongly think about that." So that's one category of patient, the one with history of major adverse cardiovascular events. Guys who have had MIs, guys who have stents are high on my list, guys with CHF are high my list, people who've had previous stroke or high on my list.

The second group of patients I have are there some patients who we're thinking that we might end up doing a limited-time or an intermittent androgen deprivation therapy approach. Now, there's less evidence in terms of the oncologic efficacy of doing that with relugolix versus doing it with an injectable agent, but the reality is that the spirit of the intermittent androgen deprivation therapy at least, is that the testosterone will recover, you'll have symptomatic improvement with that recovery, and that might make your overall quality of life better. The reality is, that with injectable, particularly LHRH agonists, that there's a good percentage, at least 10%, of men will never recover their testosterone, and many, many men will never get back to their normal level. That has not been the case with relugolix. And so, if I'm thinking about an intermittent androgen deprivation approach, I tell them that we have a little bit of a blind spot with the oncological data, but this is more akin to the spirit of letting your testosterone recover and having you feel better.

Finally, I sometimes think about the negatives of the pill, and I tell the patients that compliance can be a big issue and it can be hard to gauge as a provider. It's hard to be able to understand what the patient, how compliant are they really going to be? With my LHRH injectable agents, I usually don't check in with a patient in the time between the 1 and 3 months, the first month and the third month that I gave the injection. That's the first time, unless they contact me, I'm asking them about hot flashes, quality of life, et cetera.

With relugolix, because of some of the experience I've had now with patients taking oral antiandrogens and other pills in the later disease setting and having been a couple of times exposed to actually poor compliance that leads to bad outcomes in those patients, I'm strongly, and actually already implementing, a month in asking them, "Well, how many pills have you really taken?" And try to make a safe space so I understand, have they been compliant or not? And if I sense or ask them, "How do you do with your other medications? How much polypharmacy? What's your method for a pill box or other type of method for this?" And they just say, "It's always been a struggle." That might be a reason for me not to reach for the medication.

Alicia Morgans: I think that's so interesting because I completely agree. As a medical oncologist, I use a lot of oral agents. We've had abiraterone and enzalutamide for many years now, and of course we have apalutamide, darolutamide now as well, we've got PARP inhibitors for those patients for whom they are appropriate. So I have used these oral agents and I actually always check in with people at a month and I ask them how it's going. I also check lab work. And so I think in this setting, we can check testosterone, and because the recovery is so fast, if patients are really non-compliant, they may not have complete suppression of their testosterone, which we would be able to see on that laboratory test.

But I think it's great, I completely agree with that approach, where we check-in, and as you said, make a safe space because it's okay if you find that you can't be compliant or you don't want to be compliant. I think that's an opportunity for a conversation because maybe an injectable is a better option, maybe there's something more, maybe the side effects are bothering you, maybe there's something we can do to support you. So I think that's actually a great thing to do, and it makes a lot of sense in the setting of an oral agent. So all of that sounds good, and I would agree with those patient selections.

I wonder, how does that conversation go? If you're starting in a new patient on, on one of these agents, I think those conversations are relatively easy, and as you kind of alluded to, we bring it up, we particularly talk about it with patients maybe with cardiovascular disease, anyone who has a cardiologist, this is a conversation we have. But for patients who have had this ongoing relationship with a GnRH agonist or whatever injectable that they're receiving, how are you having that conversation with them? Are you having that conversation? What does it look like if you are?

Ashley Ross: So, in that setting, I had picked the patients that had the most cardiovascular risk, and so far, I've only made it to that conversation twice with switching patients. One gentleman had almost symptoms, to me, that seemed like, and he wasn't sure, but maybe still some residual defects in potentially some angina., And actually we ended up sending him in to his cardiologist. He's getting evaluated, he has an extensive cardiac history. I told him that I would really prefer he switched agents. Now again, there's not a lot known. It's unclear to me, and I think there's more research to be done, on, what is the biggest time where plaque gets mobilized? When's the biggest time where it forms? Is it when you switch, can you recover some of the function? Or is it something where you'd rather start with a GnRH antagonist and then switch to an agonist? Is that the way to do it?

But regardless, I told the person, it can't hurt, it might help. And he talked to this cardiologist and others, they agree that there might be less cardiovascular risk with it, but at the end, he felt so comfortable getting the injections, even though there's this assistance programs now, he wasn't sure how the billing would end up for his Medicare, and he decided to stay with the injectable agents. So that conversation was not successful to my goal, but at the same time, it was interesting to go through his thought process with it. And like you said, people are very familiar and there are still holes in the data. Because what's unknown is if I switch to the oral agent and then we'd end up maybe giving him a therapy holiday at some point, who knows if his testosterone will recover, how much real benefit it would have.

The other patient where we've had the conversation that we're going to switch and it's going to be a success, is a patient who has progressive disease in terms of just relevating PSA. The guy is going towards CRPC, we checked his testosterone and his testosterone was creeping up. Instead of being where it had been around 30 or 20, it now was approaching 50, it was like 48. And so we said, "Look, as the backbone of your ADT, let's at least try to move you to relugolix so that we can get your testosterone more suppressed." And that might be a reason for us to then recheck one more PSA, because there's no clinical progression, before we think about intensifying therapy with another agent on top of androgen deprivation.

So that person, we haven't fully gotten to the end of the road with, but I think we're going to make the switch. There's a lot of rationale there for my first gentlemen, again, they looked at the logistics as a little bit daunting, the evidence is not as concrete as they wanted, and they just felt that they wanted to stay with their injectable.

Alicia Morgans: I think those are actually both successes. You said the second one was the success. It was a switch, but I think these are both successes because you had real frank conversations with patients, you talked about the data, and then the patient was able to really make a choice. And it's nice, I think, to have this opportunity to have those conversations, to share the data that we now have, and to give patients the autonomy, that choice that they can make. So, that's actually fantastic, and I love that you're able to do that in your clinic.

In my clinic, what we've been doing for patients who are on longer-term therapy, because sometimes the timing can get a little tricky, is that I've talked to a lot of patients about this particular approach, some of the pros in terms of cardiovascular risk. And for those people who are interested in trying, we're having a check-in, even if we're on more of a 3-month followup basis, we're checking in about 1 month prior to their planned injection, we're doing a tele-health at that time, we're, if they still feel comfortable, putting in the script, and we're seeing how that prior authorization process goes. And if they get their bottle of pills before that next appointment, we're having them come in for that next appointment, doing lab work, and then they're going home that night and starting their relugolix, because that's when they would have been due for their injection.

So, I think there are all kinds of approaches, but we're all going to have to kind of figure this out as we go, and for patients who do want to switch, giving them a little lead time, because we, at this point, are not 100% sure if that prior-auth process has been helpful, in my clinic, at least. As you're trying to engage and get patients this medication, have you had challenges with getting authorization? Has that been smooth sailing? Are there ways or strategies that you have of trying to get the drug actually in the patient's hand?

Ashley Ross: I think a few things. One, just to highlight, I think the approach that you were taking is phenomenal and I had not thought of thought about that, because it takes a little bit of foresight and things and I think that's something that I'm going to incorporate into my practice. Second, early on, it seemed like a little bit of a black box to me. I think that one time we made a mistake of trying to put a patient on it, we ordered it through their normal pharmacy, and they were looking at us like we had two heads and we got a little bit frustrated.

And then, we're at the same institution and you had actually trailblazed this for the institution, so we talked to some of your advanced providers and said, "Well, how are you guys doing it?" They'd linked us in with a specialty pharmacy, and we had talked to Myovant and the Myovant team and their representatives. That's, to me, one of the large purposes of the sales rep, is actually to both help you navigate that and help you get patients to the drug, and second, to inform you of these programs for authorization.

So once we got plugged in with our specialty pharmacy, we're kind of blessed that they're doing a lot of that leg work that they've collaborated well with the relugolix team, and it actually has been fairly seamless. Even for a patient that I had who really needs almost instant castration, like I was actually thinking of giving him ketoconozole, but his status of some of his liver function, I just wasn't sure and I thought it might be too aggressive, he didn't want to have an orchiectomy, he's an older guy, didn't want to go to the OR, and we had an easier time with our specialty pharmacy getting relugolix started than we did getting authorization for Firmagon, or degarelix. So that was a testament of how good our pharmacy has done things here, but I think it does take a lift, it does take a champion, in our case at Northwestern, you were our champion and our specialty pharmacists were with you on that.

And I think that for the providers out there, what I would suggest, is to work with either the specialty pharmacy that they've already been working with for their enzalutamide, for their Abi, or work with the relugolix reps closely and tell them that, "This is your job. You have to figure this out for me." And they should be highly motivated to do that, actually, and I would say, and hopefully if they're watching they'll forgive me, it's okay.

I think I was rather aggressive with them on the last conference call we had about them really holding my hand, making sure everything is perfect for the first 5 or 10 times, because if the data for the approval for the FDA, I think, was strong enough that this drug should be in the routine compendium of our practices and it can't be completely onerous on the provider side or the patient side each time and there also can't be this cloud of uncertainty, which is why your approach of, "Let me preplan for this a month before so no one's frustrated," is much better than my approach of, "I need this now, and let's figure it out." And so I say kudos for that.

But the second is I think that everyone wants to work towards that same goal. So it's been easy for me because you trailblazed it, but I think work with your rep, work with the specialty pharmacies, don't expect the pharmacists out there at CVS to know about this at all. They will eventually, but right now, no.

Alicia Morgans: Yeah, I would agree with that. And the only way I came up with my approach was actually after trying approaches similar to yours. And it gets frustrating, so we have to devise ways to work around it. I've actually tried to get the patients to help with that a little bit, which is why I say, "Look, let's have a talk. Let's talk a month before. We're going to make your appointment, then we'll also have an appointment in 3 months when you're actually due. And if you decide to change your mind or if there's any delay in getting this approved, then we'll have that little forewarning before you actually need your injection." But believe me, the drug's only been out for a couple of months and so I've tried your approach several times as well, and sometimes it can work, but it does usually take a little bit of time, just like it does abiraterone, enzalutamide, apalutamide, darolutamide, any of these agents that we have to send through for the specialty pharmacy.

Ashley Ross: On that same subject, as you know, there are these patient assistance programs to help. One of my patients who got the drug then told me what his copay was, and I thought, "Well, have you actually used the patient assistance program or did you just pay for it?" And I had a suspicion that he had not used the patient assistance programs, and we went, again, back to the rep to make sure that that was happening. I still have some gray area around those programs, but I think they do a couple things. One, they try to ensure a low copay, or two, I think they defer or omit costs for the first, I think it's 30 days and maybe up to 60 in some patients, to basically help with all those prior auths and help us figure it out so that we're not, like my guy who had a high volume metastatic disease so he's just not waiting while we figured out to be on therapy.

Alicia Morgans: I completely agree. We don't really have the time for people to be waiting for therapy. So I do think as we continue to use these drugs more and more and as individuals and practices use these drugs more and more, this will be much more reflexive. I also think that, over time, more patient assistance programs will know about the drug and will be able to help with guidance. I know the company itself does have some pretty robust resources.

And I actually didn't think you were being heavy handed or pushy at all when you talked to the reps, because that is their job, is really to help us, and I think that they view it that way too. They were really appreciative to even hear that we had this feedback and that we needed this assistance in trying to get drugs for our patients. So I think that was all actually quite a positive experience, and communicating what you need is always, I think, the right thing to do if it helps patients at the end of the day.

So I really value, your conversation about this and your insights, and I do think it'll be important for us to update this conversation, maybe in a few months after we both have a little more experience and can perhaps give even better guidance on how to eventually get relugolix into the hands of patients for those patients who are appropriate so that we can improve outcomes for the men that we take care of. Thank you so much for your time today, Dr. Ross.

Ashley Ross: Thank you, Dr. Morgans. Always a pleasure. Happy to do a follow-up, and thank you for this opportunity. I learned a lot through it myself, so that's great.

Alicia Morgans: Great.