DR BEER: 67-year-old man who presented with metastatic CRPC. He had a prostatectomy, initially thought to have been cured, but had a PSA relapse 2 years later. Following Dr Dreicer’s recommendation, was monitored for the first 2 years of his PSA relapse and, during that time, participated in a couple of clinical trials. And while on a trial of GM-CSF, he was noted to have developed osseous metastases. So that’s when we offered him hormonal therapy.
He was very disinterested in conventional hormonal therapy and its side effects. So he was actually treated with bicalutamide monotherapy.
He was asymptomatic, remains asymptomatic today. A very active guy. Responded to bicalutamide for 3 years and then —
DR LOVE: What dose?
DR SLOVIN: Fifty.
DR BEER: 150 milligrams. This was high-dose monotherapy.
DR LOVE: And any problems, gynecomastia?
DR BEER: A little bit of gynecomastia, but really tolerated it quite well.
Then progressed, I think, with 1 additional metastasis, as well as a rising PSA, and started on leuprolide acetate followed by leuprolide acetate plus bicalutamide. And by 2008 it’s been 10 years, and he began to progress both radiographically and by PSA, and that’s when he enrolled on the Phase I trial of enzalutamide.
On that study he started therapy at 360 milligrams, which was, at that time, the dose that we were testing. We backed off to 240 after a while. And he remains on that study to this day. He’s had a complete response. His PSA was undetectable until about a year ago, and then his PSA began to rise.
DR LOVE: So Oliver, going back to biology here, why would a patient respond to enzalutamide after progressing on bicalutamide?
DR SARTOR: Oh, it’s a better drug in terms of hitting the androgen access. And I think there’s a lot of preclinical data, as well as clinical data, to say that.
DR BEER: So he’s beginning to progress on enzalutamide with a rising PSA. Imaging still shows a couple of stable metastases. And I was wondering what this group would do.
DR LOVE: Yes. I’m wondering about that, too. Matt, what do you think?
DR SMITH: So this is a great example of contemporary metastatic CRPC. This guy has a great prognosis. Right? He’s now 14 years after his prostatectomy. He had a durable response to bicalutamide monotherapy, durable response to salvage GnRH agonist therapy. He’s asymptomatic throughout the entire course of his illness. And then he’s had a spectacular response to enzalutamide. So out of the gate for many reasons, he has a far better-than-average prognosis.
I would, in this patient, attempt to maintain him on enzalutamide as long as would be reasonably possible, certainly would not stop based on PSA progression alone. I’d want to see compelling evidence of radiographic progression and, at that point, would enthusiastically treat him with a CYP17A inhibitor. And I think he’s particularly likely to respond because of his durable response to other therapies. Responders tend to remain responders.
DR PETRYLAK: I agree with Matt. The only question I would have at this point is, would you administer sipuleucel-T to this patient? Because this is a slowly progressive patient and they actually do well with immune therapy over a long period of time. He hasn’t had a corticosteroid, so that makes him a good candidate. At least you don’t have to taper him down off of prednisone or hydrocortisone. So I think that this would also be something I would consider in this patient.
DR LOVE: So what’s going on with this patient?
DR BEER: So this patient got even more interesting over time. So we kept him on enzalutamide and imaged him. There was no radiographic progression. But the PSA continued to rise quite consistently for maybe 3 or 4 months from a consistently undetectable level to about 1.5. At that time he was treated with sipuleucel-T, tolerated that therapy well.
And several months after sip-T therapy was completed, his PSA began to drop and dropped back to undetectable levels, where he is now, which is about 8 months or 9 months later.