Transcript:
Alan Bryce, MD: Let’s switch gears and talk about mCRPC [metastatic castration-resistant prostate cancer]. Dr Zhang, how have the recent paradigm shifts in nmCRPC [nonmetastatic castration-resistant prostate cancer] and mHSPC [metastatic hormone-sensitive prostate cancer] impacted how you think about mCRPC?

Tian Zhang, MD, MHS: First, it’s a continuum of diseases. Our metastatic hormone-sensitive diseases most likely progress to metastatic castration-resistant disease. What’s great for patients, as you’ve highlighted, is that there’s a wealth of options that we can help sequence for our patients. We have a lot of these trials, and many options are looking at intensifying treatments. There aren’t as many that look at de-intensifying. To this regard there’s an Alliance [for Clinical Trials in Oncology] study in the cooperative group setting called A-DREAM that is looking at de-escalation. That trial will help us decide when and who we could stop treatment on. As this continuum progresses and there’s more castration-resistant disease, and as we look at lutetium-treated patients, we’ll need to look at mechanisms of resistance and how to tackle those mechanisms. To Dr Posadas’s point earlier, we need to monitor our patients for molecular changes, whether by circulating tumor DNA profiling or multiple biopsies and sequencing. We need to think carefully about how they’re resistant to each progressive therapies in sequence.

Alan Bryce, MD: Absolutely, and it’s amazing. Backing up to the last conversation, if you do triplet therapy for mHSPC, that means first-line mCRPC can be lutetium because they’ve gotten their dosing, and they’ve gotten their antigen receptor pathway inhibitor. It’s amazing that we can potentially move it up that quickly, but this difficulty of patients falling off lines of therapy and trying to get drugs in is a shifting paradigm.

Tian Zhang, MD, MHS: There’s a patient population that has extremely aggressive disease, progressing within a year on treatment in metastatic hormone-sensitive disease. You’re right that with a triplet-treated patient, a year onto their androgen receptor blocker, they’re starting to have disease activity. Sometimes it can be symptomatic with pain and more inflammatory symptoms, but these patients need other options, whether that’s getting them another line of chemotherapy, or thinking about lutetium, supply issues aside, we need to figure out who those patients are and how we can best help them prolong their life expectancy with metastatic disease.

Edwin Posadas, MD: Some of them—the RB1-deficient patients, for example, or those with multiple loss, P10 and P53—have a more aggressive biology. But not everybody is looking for that. They walk through your door and seem typical, but after you start treating them, you begin to know that this isn’t your garden variety prostate cancer. They’re an underserved population for us. This can happen across different racial groups, but their outcomes are uniformly bad. We still need to help them quite a bit.

Transcript edited for clarity.