The Landscape of Radiopharmaceuticals and PARP Inhibitors in CRPC

In part five of this roundtable series, Drs. Irbaz B. Riaz, Chad Cherington, Roopesh Kantala, and James Ewing discuss the use of radiopharmaceuticals in the overall landscape of metastatic castration resistant prostate cancer, including new treatments and data from trials including PSMAfore. The panelists also discuss the growing number of radiopharmaceutical treatments including radium-223 and lutetium.

Watch the final segment of this roundtable: The Rise of Immunotherapy in Prostate Cancer

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Dr. Riaz:
What is your thought about the use of radiopharmaceuticals in the overall landscape of castration resistant prostate cancer, obviously metastatic?

Dr. Cherington:
I think it’s just a great addition to the armatorium of different treatment options that we have and so, it’s always welcome to have the different treatment options. Lutetium is impressive compared to cabazitaxel. As long as they have the positive PSMA. You know the weakness is if the tumor doesn’t have the PSMA on it. And then radium-223 of course, the bone only disease and the overall survival benefits with both of those, it’s going to add some value.

Dr. Kantala:
The way I discuss with my patients is you’re going to go through several lines of therapy and a few years ago, this wasn’t part of my discussion, but now it is part of my discussion about radiotherapy.

Dr. Ewing:
It’ll be interesting to see if it makes its way into earlier line treatment patients in the future and what those studies show, but certainly it’s an important part of our armatorium.

Dr. Riaz:
Yeah. I think this is a good point where the current approval for lutetium is post docetaxel with PSMAfore data coming in, I think it’s interesting on how lutetium moves in earlier lines of therapy in castration-resistant disease, and perhaps with the new trials now also in castration-sensitive and early prostate cancer.

How do you think about, now that we have two agents which are radiopharmaceuticals, radium and lutetium, do you think there’s still a patient population where we can sequence these agents one first and the other second?

Dr. Cherington:
Yeah, I think we can definitely sequence them. I think there’s a role for both of them. But just like with all these new therapies and indications coming out, sequencing is always going to be a challenging question or discussion.

Dr. Kantala:
Sequencing will be part of my practice too.

Dr. Ewing:
It’s challenging right now to know what the best sequence is. It certainly varies from patient to patient.

Dr. Riaz:
Yeah. I think I really liked your point where you mentioned that life-prolonging, our strategy has to be how to give as many life-prolonging options as possible.

I think there’s some interesting data, which is retrospective, but gives us some insights. It’s from a study where patients got radium first and then they were also able to get lutetium afterwards. So this gives us some suggestion that there are patients who can go from radium to lutetium.

I think the next question I have in my mind is how do you think about PARP inhibitors in this landscape? Do you use PARP inhibitors as a single agent when there is a HRR mutation, are you still using in combination with an NHT agent?

Dr. Cherington:
Yeah. I’m trying to use it in combination when I do find those patients, especially a BRCA2 mutation patient and trying to start them as early as possible.

Dr. Kantala:
Yeah, I agree. In combination, definitely. I’ve not done single agent yet.

Dr. Ewing:
I’ve used it in both settings, but particularly for the BRCA2, certain mutations, we’re going to try and use that up front in the triplet therapy if we can.

Dr. Riaz:
I think these are wonderful points. The way I’m thinking about reconciling the data is if a patient had received an NHT agent in the castration-sensitive state, I tend to use PARP inhibitors as a single agent. If they haven’t used an NHT agent in the castration-sensitive state in HRR-muted patients, I tend to use more of a combination. But you’re absolutely right, the jury is out. There’s no clear answer in this space.

What are your thoughts about any promising radiopharmaceutical combinations or any new targets for prostate cancer, especially in the later castration-resistant state?

Dr. Cherington:
I can’t recall off the top of my head all the different combinations, but I know there’s a few different combinations with radium and lutetium. I mean, it’s exciting. The more data we can get, the more options we have for our patients.

Dr. Riaz:
Yeah. I think this is a very exciting time for all of us in the castration-resistant state as well. I think one of the things that keep coming up is optimizing the dosing of these Lutetium compounds. I think this is an area of huge interest, and then there are newer Lutetium compounds which are just coming on the field. The landscape is changing so much now. So this radiopharmaceutical space is really launching, and I think we are going to have a separate discussion, community discussion, if you’re talking about the same topic next year.