Practical Considerations for Selecting and Administering Treatment in mHSPC
Expert panelists consider the possibility of taking a break from treatment given a patient’s response to therapy along with other unique management strategies in the setting of metastatic hormone-sensitive prostate cancer.
Transcript:
Alan H. Bryce, MD: This patient goes on to receive doublet therapy, ADT [androgen deprivation therapy]–abiraterone, and then radiation to the primary [tumor] and L2. Two years later, he’s doing great. There’s no evidence of active disease on imaging. We’ve got a PSMA [prostate-specific membrane antigen]–PET [positron emission tomography] that’s quiet. PSA [prostate-specific antigen] is undetectable. Let’s go back to Dr Zhang. We heard at ASCO [American Society of Clinical Oncology Annual Meeting] and ASCO GU [ASCO Genitourinary Cancers Symposium] and the literature more talk about treatment de-escalation. This patient says I’m doing great. Do I have to stay on therapy? How do you think through that? What do you say to the patient?
Tian Zhang, MD, MHS: This is a big challenge and a good problem to have. Many of us are facing this as our patients are having great responses. Their PSA, from a molecular standpoint, is having a complete response. It’s great to see. There are no prospective data to guide us about treatment discontinuation. A lot of trials for metastatic hormone-sensitive prostate cancer [mHSPC] were written until disease progression. Patients continued treatment until their disease progressed or if they had unacceptable toxicities. There wasn’t a predefined treatment stop. When I’m thinking about these patients in the high-risk, localized setting, we’re OK stopping systemic therapies after 2 years in this setting, which is a little more along the continuum. If his primary site and the oligometastases have all been treated definitively, then we’ll keep watching. We don’t have a lot of data, but if you’re having a lot of treatment adverse effects, then this might be a point where we could take a break.
Alan H. Bryce, MD: Fair enough. Dr Lowentritt, let me ask you. Let’s say this patient had a germline pathogenic mutation in BRCA2. Same case: 1 lesion at L2, localized disease, but a BRCA2 mutation. How would that change your assessment of this patient in the beginning?
Benjamin H. Lowentritt, MD, FACS: In the beginning?
Alan H. Bryce, MD: Yes.
Benjamin H. Lowentritt, MD, FACS: I’m more interested in the BRCA2 patient to understand where I can layer in a PARP inhibitor. From a prognostic standpoint, those patients need to be watched very closely and may progress more quickly. I don’t know if it would have dramatically changed my initial approach. I’m very interested to see the utility of starting PARP inhibitors earlier in the hormone-sensitive stage in these patients or understanding how we might be able to layer it in later. It would be a very interesting thing to know up front, but the bigger question is making sure you’re fully aware of when they do progress so you can get them on therapy.
Alan H. Bryce, MD: Dr Petrylak, you talked about first-line mHSPC studies with PARP inhibitors. A question I’ve been asked at CME [continuing medical education] events and on social media is if you don’t have access to a PARP trial but have this patient, do you consider early incorporation of platinum-based chemotherapy? Where does platinum fit in to the BRCA patient if you’re in an environment where PARP just doesn’t work? Their co-pay is going to be too high. How would you think about that?
Daniel P. Petrylak, MD: Unfortunately, there are no data, but I’ve used platinum-based chemotherapy in patients who have progressed on PARP inhibitors. I’ve seen some signals, but there’s very little published on that group of patients. We need to get studies to look at that group of patients. I don’t substitute because we don’t have the data. The only situation where I may use a platinum compound early is if I identify a neuroendocrine component to the tumor, but otherwise I’d wait until they’re metastatic and refractory. Can I get back to the previous case for a moment?
Alan H. Bryce, MD: Yes.
Daniel P. Petrylak, MD: The team brings up some very interesting issues. I’ve got a couple of patients in clinic where who’ve had biopsy-proven metastases. We’ve used the oligometastatic approach and been on ADT-abiraterone for 2 years, and had no disease that we could detect by conventional imaging or PSMA scan. This is going to become a more important use of PSMA scanning: to determine whether a patient has disease. Two of these patients are off ADT and have normal testosterone levels and no evidence of disease. We need to understand: who’s the appropriate patient for this approach, and how do we best follow them afterward? Do we do serial PSMA scans? Do we just follow by PSA? They can progress either way in the situation. It’s a tough question.
Alan H. Bryce, MD: I agree. I appreciate you circling back to the point. I also have patients in whom we’ve done it. There were various reasons we’ve ended up at this point, but we’ve treated it with a complete response in the hormone-sensitive setting, and they’ve maintained response after testosterone recovery. The open question is how long that response is maintained. I tell patients, “I don’t believe you’re cured. It comes back eventually, but it could take awhile.” The point, as I talk about treatment discontinuation with patients, is that there’s no reason to think that the disease recurs explosively. I’ve never seen it. It’s a slow disease process. It will come back slowly. As long as we do follow-up and close surveillance, the patient isn’t going to get into trouble. The only way that patient is going to get into trouble is if they’re lost to follow-up and come back 2 years later when they’re symptomatic. If we’re doing a PSA every couple of months, we’ll catch these patients before they have symptomatic disease, and we’ll have the opportunity to get back in. It’s a question for future trials. We have to figure out who’s the best candidate for this and how best to do it. But in terms of safety, it’s there. Of course, there are the symptomatic patients with adverse effects, so stopping therapy for consideration of toxicities is a consideration for them.
Benjamin H. Lowentritt, MD, FACS: The only thing I’ll add is a note of caution. You see a lot of prostate cancer. These patients live the longest and cluster with you a little, so it feels as if there are a lot of them. But it’s rare. What I see a lot more often is patients prematurely stopping their ADT or other therapy because they did OK for 2 years and then just stopped. To a lot of us in the audience, it’s important to say that this is the minority of patients, unfortunately. We hope there will be more. For most patients, staying on therapy to progression is definitely the course. You’re going to find these. Maybe they’re not unicorns. Maybe they’re a little better, a little more frequent. I always caution about that because I’ve seen many [patients for whom] it’s not necessarily explosive unless they didn’t follow up for 9 or 12 months and stopped their therapy. Then it’s fairly explosive. Just a note of caution there. But I completely agree that it’s exciting to take a patient off therapy when you thought that was never going to be an option for them.
Daniel P. Petrylak, MD: Both of these patients are not short term. These are long term. One is a 3-year [patient], and the other is 2 [years].
Alan H. Bryce, MD: It’s a long term. Absolutely.
Transcript edited for clarity.
