AR-targeted therapies for nmCRPC


Julie N. Graff, MD, highlights the efficacy associated with the use of androgen receptor inhibitors for nonmetastatic castration-resistant prostate cancer.

Benjamin H. Lowentritt, MD, FACS: That discussion got us into the nonmetastatic castration-resistant space, which is a whole other animal to talk about.

Julie N. Graff, MD: Yes. With nonmetastatic castration-resistant disease, I remember we used to try bicalutamide, then we would try bicalutamide withdrawal, then we would try high-dose bicalutamide, and then we would use ketoconazole, estrogen patches, and all this voodoo. And then came the SPARTAN trial, which was the first trial I was aware of using apalutamide in patients who didn’t have metastatic prostate cancer, but their PSA [prostate-specific antigen] was rising despite castration.

The primary end point for that study was metastasis-free survival, so the FDA approved an end point that we hadn’t seen before in prostate cancer: the delay to time of spread. I and many others were very dubious about that end point because the first metastasis is not often a painful, devastating metastasis, like breaking your hip. We’d normally do imaging studies until we saw something and then put people on AR [androgen receptor] antagonists. When the overall survival benefit came to light and people were living longer because we were starting these drugs in the nonmetastatic castration-resistant setting, then I was much more of a believer. Because before, we were wondering if we were impacting someone’s quality of life without a very meaningful end point. But now the data are clear that these medications are very useful.

I’d like to add something. With these additions, first we use these drugs after chemotherapy in metastatic castration-resistant prostate cancer, but now the indications are you do it right away if it’s metastatic or as soon as it becomes nonmetastatic castration-resistant. People are going to be on these drugs a lot longer. If you look at SPARTAN, people were on these drugs for almost 3 years. Everything we know about the harms of castration are probably going to be amplified in terms of bone loss, muscle loss, weight gain, and fatigue. We also have to factor that in when we’re talking with our patients.

Benjamin H. Lowentritt, MD, FACS: That’s a great point. At this point, starting the medication is the easy part. It’s the discussion around not just the adverse events—we’ll talk a little about some of the quality of life stuff—it’s the long-term questions to other systems, whether it be metabolic syndrome, cardiac, or even just pain and, as you said, atrophy of muscles and the like. It’s a challenge that we’re not doing our patients justice if we’re just thinking in terms of their PSA effect and latest scan. That’s the wonderful thing about having agents that keep patients alive longer. It’s also the really intimidating thing about taking care of these patients long term.

Transcript edited for clarity.

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