MFS as a Clinical Endpoint in nmCRPC

Transcript: Judd Moul, MD: I want to bring up the metastasis-free survival. Alicia, you did an excellent job of articulating that these agents extend metastasis-free survival, on average, by about 2 years. One of the things I hear from some urologists that I talk to is, “There’s no survival benefit, therefore, why should I use an expensive agent that may have adverse effects on my patient who’s doing well clinically with no obvious metastasis when there’s no survival benefit?” Then, I’ve heard people say, “Well, if I pull the trigger for apalutamide or enzalutamide early, then by the time they progress, they’re going to be so beaten up that when I refer them to medical oncologists, nothing is going to work.” I was going to get some perspective. How do you address this issue of no overall survival benefit?

Alicia Morgans, MD, MPH: I would say the data is just immature at this point.

Judd Moul, MD: OK.

Alicia Morgans, MD, MPH: We’ll have to discuss SPARTAN in a second, too. The ARAMIS trial, which was looking at darolutamide in this nonmetastatic CRPC [castration-resistant prostate cancer] population, also had a primary endpoint of metastasis-free survival, but had a secondary endpoint of overall survival, just as they all did. That one got a little closer to having enough events to potentially demonstrate an overall survival benefit. There’s a trend in that direction. It’s clearer in that study, at least as the data was reported, that there’s a trend towards overall survival. I hope we’ll see that in SPARTAN and PROSPER, as well, but we don’t know yet. Until that survival data is mature, that’s an incredibly valid point.

I think about things in addition to survival. What was really interesting to me is that in these trials, they demonstrated a maintenance of quality of life. In the ARAMIS updated data at ASCO [American Society of Clinical Oncology Annual Meeting] 2019, they also demonstrated an improvement in quality of life, particularly in the bowel and bladder domains of the quality of life measures, which is interesting. That was interesting to me because I thought, “How does a systemic therapy specifically improve these domains that are typically driven by localized progression, which is not something I typically think would happen.” The ARAMIS trial, interestingly, enrolled many patients who were outside of North America and outside of the United States, so they didn’t necessarily have treatment of the primary prostate.

Judd Moul, MD: I find that really interesting. Most urologists, or the vast majority of clinicians who are prescribing either enzalutamide or apalutamide for nonmetastatic CRPC, make the assumption that these patients all had previous surgery or radiotherapy. Do any of the panelists know what percentage of patients in those 3 trials did not have their primary treated?

Alicia Morgans, MD, MPH: I looked recently at the New England Journal of Medicine paper for ARAMIS and it’s not reported, at least not that I could find. I don’t know that it’s reported for the other 2, so we’d have to see that. I also didn’t see quality of life data for the other 2 trials that pulled out specific domains, other than pain, that were improved. All of these did seem to have a longer time to pain progression, which is also interesting. All of that needs to be fleshed out. It’s an interesting question, and not one that’s been discussed at length yet.

Transcript Edited for Clarity