Alan Bryce, MD: Your description is nice, how did the patient show up to the party? I think part of the good news here is we have an answer regardless of how they showed up. Have they been exposed to a prior androgen receptor pathway inhibitor [ARPI] or not? We can give them monotherapy. We now have some data supporting the combination therapy. I’ll throw a point out there, and I wonder how the panel feels, which is people talk about the 3 combination studies as a group, but we have 3 different PARP inhibitors and 2 different ARPI partners. I would never mix and match among these. These are set pairs, 3 standalone studies, and with the drugs being so different, I don’t think the PARP inhibitorsare interchangeable. Maybe that’s a debatable point, but I think they’re different chemically, so I wouldn’t mix and match or compare across the studies. I would examine each study separately, right?

Elisabeth Heath, MD, FACP: Honestly you shouldn’t do it anyway, which is why our earlier conversation was interesting, when it’s an indirect comparison. If you think about other cancers, and certainly we have Dr Zhang who’s a total renal expert, talk about lots of doublets there that have their own standalone trial, and yet what do I do in the clinic when these patients come in? It’s the nuancing of this person has this, this person has brain metastases. We do that in our kidney cancer population, and then you go, ah, that’s my doublet. But not everyone there in kidney cancer shows up to the party in such a heterogeneous way like our patients with prostate cancer. Part of the struggle is to try to figure out for every instance, what if you had this, and what if you had that? I think…did a great job with, if you showed up with this, you can go here. What I worry about is that we’re expert prostate folks, we think about this all the time. But for a person in a busy practice who’s seeing all sorts of cancer types and must figure out who showed up, when it was a lot simpler in the past, now you’re trying to integrate this, and let‘s not forget whether you did genomic testing or you didn‘t because that seems like mixed messaging too—it gets complicated. Do I think they’re the same? No. Are they the same class? Sure, but I think many of us who do drug development know we never lump them all together. They’re in the same class, but it doesn’t mean they’re the same.

Alan Bryce, MD: Fair.

Edwin Posadas, MD: I’d push even beyond that because the responses by the HRR [homologous recombination repair] deficiency are also quite different. ATM was a big disappointment for the field, even though it got lumped in with BRCA in the beginning. With all the studies, if you take a big step back, it puts PARP on the map for prostate, it’s here to stay. We’re going to have to get smarter with it, and the field will have to start adapting to doing some molecular testing for the benefits. Dr Bryce, I think your data, when you looked at the docetaxel versus rucaparib effect, it was striking that you were getting to a fundamental problem in the patient’s biology. Again, the positive message is there’s hope that we’re getting smart enough to use biology to our advantage. We’ve just got to come up with the right hypothesis and get the signal from the noise we have in our trials, but fortunately we’re not too bad at that.

Benjamin Lowentritt, MD, FACS: I also think we’re getting more safety data of these combination therapies, which shouldn’t be lost for wherever we end up using them. Unfortunately, the patients in these roles who are the ones with mCRPC [metastatic castration-resistant prostate cancer] are no longer hopefully what we’ll be seeing as the patients with mCRPC going forward, because they will have gotten more therapy up front. What we’re learning is that the drugs don’t have, or maybe do have in certain cases, signals that they should or can be used together. I think that’ll help us no matter what because I agree, they’re here to stay, and we’ve got to get comfortable with them because they’re probably, for the right patient, they’re going to be great.

Elisabeth Heath, MD, FACP: Can I say that we need to be clear for our audience today that we still all advocate, at least I do, for genomic testing. Although, we’re talking about data for all comers, that doesn’t mean you don’t test. I think that got lost a bit last year, where everybody confused the testing issue. To your point, Dr Bryce, these studies were also quite different in how people got in the study. One was a look back to say, what was their profile? One was a prospective approach, everybody new. One was mostly tissue with a little blood. They weren’t all the same blood tests. Some were germline, some were not. That is confusing for the practicing clinician, but I think the message here is you test germline and somatic, if you can.

Tian Zhang, MD, MHS: Absolutely. I can’t agree with that more. There are patients we miss, patients who have low tumor shed in their bloodstream, their ctDNA [circulating tumor DNA] doesn’t pick it up on the first go around. I’ve seen it where we biopsy the tissue, especially if it’s a visceral metastasis, I’ve had liver metastases where we biopsied and ctDNA has been negative, and we biopsied the liver, and that has come back with that BRCA2 alteration. How much can we help our patients if something doesn’t look right and doesn’t feel right? That’s the art of medicine that you all were talking about earlier. But if it’s not the run of the mill disease and if it looks off, then I’m a strong proponent of testing and sequencing to find that genomic answer. With the all-comers conversation of these PROpel and TALAPRO trials, I’m not totally sold that everybody needs PARP inhibitors plus an AR [androgen receptor]-targeted therapy in unspecified patient populations. I still think the benefit we see is higher when patients have HRR alterations.

Elisabeth Heath, MD, FACP: Dr Bryce, one of the interesting things that came out of that meeting discussion also is the end points, and we got into a bit of a heated discussion about overall survival versus median PFS [progression-free survival] to anything else you want to throw in there. I think that being mindful of how the trial was designed, whether you agree or not, is a critical piece. If it wasn’t designed to answer a specific question, we can sit here and debate all we want, we’d just not get the answer because it wasn’t designed to get the answer. That’s almost a, “shoot, I wish we’d known about this years ago.” But I think that, especially in oncology, this conversation is not changing anytime soon. It depends on all of us as well as our pharmaceutical collaborators to pick the right end point so we don’t have one of these, “gosh, what are we going to do” moments, which tends to happen a lot nowadays, more than I’d like to see.

Edwin Posadas, MD: Dr Heath, to follow-up on that, it underscores the importance of getting these patients on the trials. There’s so much that we know, but it’s clear from this conversation, which is reflective of how the field feels, we still have a lot of unanswered questions that we need to deliver to get this care…into the hands of clinicians and patients to maximize the benefits we see potentially happening. But without the trials and the participation from both the doctors and the patients, it won’t happen.

Alan Bryce, MD: That’s a great point Dr Posadas, because one of the fundamental changes in our field that’s driving this entire conversation is the fact that we’re now putting a lot of patients on studies. We all remember the battle days when breast cancer could put more patients on 1 study in a year than we would put on 10 studies. Ten years ago, before abiraterone and the COUGAR studies in 2011, 2010, there was no prostate cancer at ASCO [the American Society of Clinical Oncology annual meeting]. When was prostate ever in the plenary [session] at ASCO? Now it’s like every other year. We don’t want to go back to the bad old days where no one was bothering to do studies and no one was asking questions. We need to cure this disease. The job isn’t done until every patient is cured. We’re not here just trying to extend life by a couple of months, we want the whole kit and caboodle.

Transcript edited for clarity.