Apalutamide in Treating Nonmetastatic CRPC

Transcript: Elizabeth Heath, MD: Nonmetastatic castration-resistant prostate cancer [CRPC]—that’s a tough group. You’re really trying to balance how patients feel about treating their cancer versus actually treating something you see. All you see is that PSA [prostate-specific antigen] goes up. Everyone is anxious—the doctor is anxious, the patient is anxious—but you can’t find where the cancer is. That adds to the degree of anxiety. Then you start to worry that you’re going to end up treating the number as opposed to the patient. It’s a balanced decision. But recent data really show that there are now new drugs that are FDA approved that one could prescribe.

They’re already on the androgen deprivation therapy, which has a lot of adverse effects. I think a lot of people might try oral antiandrogens, which have been around for many years. I tell you, a lot of my patients will try some nutraceuticals, or some things over the counter, or something more holistic just to try to get their PSA number down.

The NCCN [National Comprehensive Cancer Network] has now recognized that there are 3 oral agents. They’re all in the same category of androgen receptor modulators. One is enzalutamide, another is apalutamide, and most recently there is darolutamide.

These are drugs that are already approved for castration-resistant metastatic prostate cancer. They’re not drugs out of the blue that investigators and others have decided to develop. They’ve been around, and they are already FDA approved. It’s just moving it up the clinical states, earlier into the disease. It kind of makes sense, not just from a biological standpoint but from a drug development standpoint.

Matthew R. Smith, MD, PhD: In the United States, there are currently 3 drugs approved for nonmetastatic castration-resistant prostate cancer—apalutamide, enzalutamide, and most recently darolutamide. The data reported on the updated survival analysis for apalutamide provide the most complete information about the impact of that drug on survival. The other 2 studies that supported approval of the other 2 drugs showed a preliminary trend and better overall survival. But much like the primary metastasis-free survival data for apalutamide, those data are immature. So we await similarly updated results for survival of the other 2 agents.

Elizabeth Heath, MD: It’s always helpful when they’re kind of consistent with the original data set. I think the new ESMO [European Society for Medical Oncology] data are consistent with that. They give a sense of comfort that the original reporting is actually on point. What this shows is data maturity. However, not all the way. You can’t comment on overall survival, because it’s still too early. Even now, it’s still too early. It’s something we recognize, but again, overall survival was never the primary end point, although we still like to see it. In terms of looking at that interim analysis, it gives us all comfort, as practice physicians, to say, “Oh yeah, the data are actually holding up over time.” I think there are no surprises with the secondary end points either. Again, a sense of comfort that the data will hopefully, as they continue to mature, stay exactly as it was reported.

Matthew R. Smith, MD, PhD: In SPARTAN we measured progression-free survival 2, or PFS2, as an exploratory end point. PFS2 is defined as the interval from study entry to progression on subsequent therapy, with the notion being that if you intervene early with apalutamide in the control group patients may possibly catch up when they went on to subsequent AR [androgen receptor]—targeted therapy or other treatment, for example.

And so PFS2 is an attempt to understand whether patients were able to catch up by getting later salvage therapy. The significant improvement in PFS2 really clearly demonstrates, in my view, that patients didn’t catch up. With this updated analysis, we reported at this meeting, for example, that the risk of PFS2 was reduced by about half; and PFS, median PFS2, was a year longer in patients initially treated with apalutamide. This clearly shows that there’s an additional supportive evidence for early intervention with apalutamide and provides good evidence that patients who are initially observed or, in the case of SPARTAN, treated with placebo, do not catch up with later treatment.

Alicia Morgans, MD, MPH: PFS2 is a little bit of a complicated end point that looks at progression after the second treatment in the SPARTAN trial. It’s an important end point, but 1 that I think we still need a few more details on to really understand whether the timing of these active treatments matters. It does imply that the earlier we treat patients with nonmetastatic CRPC, the longer the duration of therapy is going to be and the longer we’ll be able to prevent metastatic disease.

Transcript Edited for Clarity