Metastatic CRPC: Novel Treatment Strategies With Radioligand Therapy


Key opinion leaders share insight to novel combination strategies and clinical trials focused on radioligand therapy in metastatic castration-resistant prostate cancer.


Rana McKay, MD:It’s interesting to see this combination radioligand therapy. We have the radium-olaparib study. Phase 1 has been conducted, the phase 2 is ongoing. At this year’s ASCO [American Society of Clinical Oncology Annual Meeting], we saw data from the olaparib study with lutetium.

Ulka Vaishampayan MD:Yes.

Rana McKay, MD:What are your thoughts on that? There’s a very interesting dosing paradigm with olaparib. Looking at intermittent olaparib dosing … lutetium.

Scott Tagawa, MD, MS, FACP:There are different perspectives. If you’re a company that sells PARP inhibitors, you want to find some way to make that work. This is looking for a way; it’s essentially a radiosensitizer. If you’re causing single-strand breaks with the beta emitter, don’t allow it to repair itself. That makes sense. What do we want from phase 1? We want tolerability, and it appeared to be tolerable. We’ll see what happens in phase 2. The most important thing for the phase 1 trial is to show safety and come up with the dose. I wasn’t overwhelmed with the responses, so we’ll see.

Ulka Vaishampayan MD:I agree with that.

Rana McKay, MD:More to come, but it’s exciting to see that these drugs are being tested in combination with novel strategies in that regard.

Sumit K. Subudhi, MD, PhD:Can I ask Scott a question? We’re seeing the next-generation radioligands going to actinium as 1 possibility, but are we thinking about changing targets and not just focusing on PSMA … ?

Scott Tagawa, MD, MS, FACP:Yes. A small group of us have been doing this for a long time, and more are joining in. We have 2 validated targets, hydroxyapatite bone and PSMA. We can improve on what we have by having additional agents, whether the target age is different and radio colitis is different. We have a number of cell service targets. When I’m talking to my patients, I say we can target this in 3 ways. We can bring in radiation and come with a drug and a drug conjugate—for instance, in the immune system. Whether it’s a CAR [chimeric antigen receptor] T cell or bispecific, we have multiple ways of targeting these different cell surface targets.

Rana McKay, MD:It’s superexciting.

Ulka Vaishampayan MD:I have a question. Are they multi-targeted radioligands?

Scott Tagawa, MD, MS, FACP:There can be. There are constructs that are 3-armed. Those are intended to be 2-armed, but you could switch out. The most recent PET [positron emission tomography] approval was a radio hybrid for the PSMA [prostate specific membrane antigen]–targeting part. Then there’s radium, so you can have F 18 or gallium. It’s not designed to use both at the same time, but in theory you could.

Transcript edited for clarity.

Related Videos
A panel of 4 experts on bladder cancer
A panel of 4 experts on bladder cancer
Jeremy L. Ramdial, MD, assistant professor, Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center
A panel of 5 experts on renal cell carcinoma
A panel of 5 experts on renal cell carcinoma
A panel of 4 experts on hematologic malignancies
A panel of 4 experts on hematologic malignancies
Neil D. Gross, MD, FACS