A Look Into The Future of PSMA-Targeted Therapies in Prostate Cancer


Panelists review the recent FDA approval of the PSMA-targeted therapy Lutetium Lu 177 vipivotide tetraxetan for patients with metastatic castration-resistant prostate cancer and discuss additional settings in which it, and other PSMA-targeted treatments, might be used in the future.


David Albala, MD: Let’s talk about how PSMA [prostate-specific membrane antigen]–targeted therapies such as lutetium might improve outcomes in patients with prostate cancer. Gary, why don’t you take that? Then we can throw it out to the whole panel.

Gary Ulaner, MD, PhD, FACNM: Thank you, David. I like to refer to this field as molecular imaging and therapy. We image what we treat, and we treat what we image. The purpose of having these agents is not only to see the tumors but also to target them with enough radiation that we can affect a cell kill. The only FDA-approved PSMA-targeted therapy is lutetium-177–PSMA-617, which was published in the New England Journal of Medicine in the VISION trial. That trial demonstrated an increasing survival for patients who’ve had both hormonal and taxane chemotherapies. This is just the beginning. There’s going to be much more to say on PSMA-targeted therapies, different constructs of the molecule that binds to PSMA, altering the radiation emitter from lutetium-177 and other beta emitters to alpha emitters like actinium-225, a combination of PSMA-targeted therapies with other forms of therapies, and timing of the therapy in the course of patients’ disease. These will all be areas under hot investigation in many current and upcoming clinical trials.

David Albala, MD: Gerry, what patient populations is lutetium used in? Do you think it might be used in the future earlier in therapy?

Gerald Andriole, MD: Gary mentioned the VISION trial, which used patients who had already failed the conventional therapies, including chemotherapy, and androgen manipulation. There’s no doubt in my mind that we’re going to be moving this therapy earlier and earlier in treatment-naïve patients who have metastatic disease. The exact treatment modality, whether it’s exclusively a beta emitter or a combination of a beta and an alpha emitter, might depend on the distribution of metastases that the patients have. The dosing, the timing, and the sequencing of this therapy with other therapies is totally unknown at this point. That will be the subject of a lot of ongoing clinical research in the very near term.

David Albala, MD: Ashley, what are your thoughts on lutetium?

Ashley Ross, MD, PhD: They’re extremely promising agents. When they started therapeutically, like in the VISION trial and the somewhat smaller trials, it was at the end of the disease state. As we mentioned, PSMA is an antigen-regulated gene. There are times in the disease course when expression is thought to be more. As Gary pointed out very strongly, it’s not going to be just 1 drug. It’s almost like when we were talking about tracers: you’re not going to think I’m just going to use my lutetium–PSMA. There are going to be differences in the compound itself—how does it bind the PSMA, is it a small molecule, is it a “minibody,” is it an antibody? There are going to be differences in the tracer; that would be the therapeutic payload. Is it a beta emitter? Is it an alpha emitter?

We also have to think about the biology of when to deliver it. Is it when the disease volume is greater? Should we debulk the disease and then deliver it? How many cycles are we giving of the drug? There are all the combination therapies that Gary is talking about. If we think back to radium-223, which was a bone-targeting agent, there are some data, but a lot of the combination trials are yet to be reported, and they’re going to blow the field wide open. We’re at the tip of the iceberg with the survival benefits we saw in VISION.

As we go into the hormone-sensitive setting and the early castration-resistant setting, the value of doing the imaging is going to become even higher. If anything, we’re going to do even more PET [positron emission tomography] imaging with FDG [fluorodeoxyglucose]-PET and PET PSMA in later states to see who’s going to be a better treatment responder. As we talked about earlier, maybe we’ll get more standardization of how they read the studies because that’s going to become even more critical for therapeutic selection early on. That’s where the field is wide open. As you said, in terms of staging and imaging, everybody should jump on the bandwagon and do that. In terms of how we do it for treatment, there’s so much to do. My gut tells me that we’re going to see really good results.

David Albala, MD: This has been great. For the audience, if you’re able to get the Urology Times® from September 2022, there are 2 superb articles, 1 on PSMA and MRI for early detection of prostate cancer and a second on PET imaging for advanced prostate cancer. Many of the points discussed today are illustrated in those articles, so they’re great references. As we look to the future, this is the imaging modality of the future for prostate cancer, in my mind. It’s time to jump on the bandwagon, incorporate it into your practices, ad use it appropriately. It will give you great information and may change how you treat these patients. That‘s the real takeaway message.

We’ve covered a lot of ground tonight; I want to thank Gerry, Ashley, and Gary for spending the time with me. For our viewing audience, I hope that the viewpoints and information we’ve discussed were informative. I recommend looking at Urology Times® from September 2022. Thank you very much.

Transcript edited for clarity.

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