Implications for Treating With AR Inhibitors in M0 CRPC

Jorge Garcia, MD:The metastatic castration-resistant setting is that unique setting, in the sense that we now have 6 life-prolonging agents for these patients. The M0 [nonmetastatic] space is a much more complex patient population, because they’re healthier and don’t have any evidence of disease on scans. So there is concern about how much impact you’re going to have on someone’s quality of life for the benefit that you’re going to have. I think the metastasis-free survival data for the 3 existing agents is something that is very hard to ignore. My biggest question is going to be, I really want to see the survival data mature and see if it really impacts mortality from prostate cancer in that patient population.

I also believe that the M0 space is something that has been created by us, specifically when you initiate androgen deprivation therapy [ADT] in men without metastatic disease—that’s what we call the biochemical recurrent setting, or nonmetastatic setting in the castration-naive disease space. So I think that is induced by what we do. And lastly, I do believe that the M0 space is likely to continue shrinking over time, just by virtue of new imaging technologies. We now have fluciclovine PETs [positron emission tomography] and PSMA [prostate-specific membrane antigen] PETs. The likelihood of those new emerging imaging technologies to detect even disease that we didn’t think one can have before is significant, which means that it’s very possible that with new imaging, the M0 patient population will not be M0. Rather, it will be M1 in nature.

The use of this class of agents earlier in the natural history of prostate cancer has actually really changed how we practice. We now know that the addition of apalutamide, abiraterone acetate, and enzalutamide are part of the standard of care for men with castration-naïve or castration-sensitive disease, regardless of volume—even high or low volume disease. And there’s a trial called ARASENS that will define the triplet therapy combination of darolutamide, docetaxel, and ADT against ADT and docetaxel for men with de novo metastatic disease.

Perhaps, if you think even further, the use of this class of agents even in the neoadjuvant or adjuvant space, or when we use AR [androgen receptor] inhibitors in combination with radiation therapy—whether it’s in the adjuvant or salvage space—is something that we’re actually looking at right now in clinical trials. I think it will repave, again, how we manage our patients early.

Oftentimes, the question in prostate cancer is timing of treatment. So the bigger question is, with the early introduction of these agents, it is very likely that may change the biology of one’s disease. But yet, the bigger question is, is it really destined to change natural history, and therefore mortality from prostate cancer?

Transcript edited for clarity.