Metastatic CRPC: Novel Treatment Strategies With Radioligand Therapy

EP: 1.Overview of Metastatic HSPC: Diagnosis and Risk Stratification

EP: 2.Systemic Treatment Armamentarium in Metastatic HSPC

EP: 3.What is the Role of Locoregional Therapy in Metastatic HSPC?

EP: 4.Informing Systemic Therapy Selection With Negative Data in HSPC

EP: 5.Evolving Treatment Landscape of Nonmetastatic Castration-Resistant Prostate Cancer

EP: 6.Advent of PARP Inhibitors in Metastatic CRPC

EP: 7.Combination PARPi Strategies in Metastatic CRPC: Interpreting Data From Clinical Trials

EP: 8.Radioligands in the Treatment of Metastatic CRPC: Lutetium-177–PSMA-617

EP: 9.Radioligands in the Treatment of Metastatic CRPC: Radium-223

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EP: 10.Metastatic CRPC: Novel Treatment Strategies With Radioligand Therapy

EP: 11.Novel Therapeutic Targets in Metastatic CRPC

EP: 12.Potential for CDK4/6 Inhibitors in Metastatic CRPC

EP: 13.Ongoing Clinical Trials in the Metastatic CRPC Setting

EP: 14.CAR T-Cell Therapy in Metastatic CRPC and Future Directions in Care

Transcript:

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.