Novel Treatment Modalities in Metastatic Hormone-Sensitive Prostate Cancer

Transcript:

Alan Bryce, MD: Dr Posadas, what else is coming in the mHSPC [metastatic hormone-sensitive prostate cancer] space, clinical trials, other combinations, what are you excited about?

Edwin Posadas, MD: I’m almost ashamed to answer this after you’ve been a big part of PARP inhibitor development therapy. We’re starting to see some significant advances down molecular avenue, certainly there’s a lot of interest with TALAPRO, PROpel, and other studies looking at the role of PARP inhibitors that are leaving us asking a lot of questions. It’s the same thing we are talking about here, the risk-benefit ratio for the patients, who do you choose, how do you choose them? Are our tools appropriate? At this point I would still answer we’ve got some insight but not enough, and that’s only one example. Going back to the beginning of our discussion, PSMA [prostate-specific membrane antigen]-targeted therapy has been such a big hit in the castration resistant state. Patients thank me endlessly for being able to get them the lutetium conjugates we’re using. But there’s a demand for it now in the earlier disease spaces. There is an ongoing study, PSMAddition, that will look at lutetium PSMA-617 in the castration-sensitive space. I think that will answer a lot of questions for us about who it can benefit in treating these patients.

The good news is the patients are talking not only about the benefit, but the harms. I counsel them endlessly on the risks of xerostomia as part of this process, and I’m glad I don’t have to shock with them with that news. But at the same time, being able to navigate that for them is not easy. Another one, since we touched on deintensification of treatment, that’s also out there that I think will be insightful is the NRG-GU011 study, PROMETHEAN, which will look at the role of metastasis-directed therapy in the oligometastatic castration-sensitive space. This is a new space that’s been born from PSMA-based imaging, but how to aptly manage them, especially given early data in trials like ORIOLE and STOMP saying that oligometastatic prostate cancer benefits from metastasis-directed therapy. I think may spare our patients from being on prolonged if not intensified ADT [androgen deprivation therapy], which should positively impact quality of life, provided that we don’t compromise survival.

I think that new field has opened up, and other combinations with drugs like abemaciclib, which has a stronghold in the breast cancer world, but for reasons of related biology it may be helpful in diseases like prostate cancer in combinations with drugs like abiraterone in the CYCLONE 3 study. This is I think, again, poised to have us relook at these castration-sensitive patients and say, how do we optimize treatment not for everyone, but for a patient in particular based on clinical factors and molecular profile? I’m very excited to see those data coming forward.

Alan Bryce, MD: So much to come, right? It’s the great thing about our field, every 6 months we’re doing something different, aren’t we?

Transcript edited for clarity.