Targeting PSMA in Prostate Cancer Treatment - Episode 5

Lutetium-PSMA-617 for Prostate Cancer Treatment

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A discussion on the use of lutetium-PSMA-617 for prostate cancer treatment.

Alicia Morgans, MD, MPH: Phil, what is your reaction to the VISION data? And of course, with that approval, what are your thoughts in terms of lutetium-PSMA [prostate-specific membrane antigen]-617?

Phillip J. Koo, MD: For those in the nuclear medicine committee, we've been talking about theranostics for a really long time. You would see a lot of these single-site studies, retrospective studies from Germany, all across Europe, Australia, and other countries, which showed amazing results. We've all seen those amazing pictures of patients who had diffuse disease who all of a sudden just had this amazing, complete response on imaging, which really got so many of us excited. For those of us in the nuclear medicine committee, we've waited for so long, and it was the validation of the great work that so many people had put in. One of the unexpected components of the approval was the specificity of which diagnostic agent you would get before you qualified to get PSMA-617, the lutetium. They specified in the label that it had to be gallium-68-PSMA-11. In many ways, that made sense, because in the VISION trial, every single patient did receive the PSMA-11, but in real life, we know that we had 2 agents available in the United States that are pretty much identical. We saw in the chemical structures that they almost are identical, but their biodistributions are the same, and their performance is pretty much the same. They have always been thought of interchangeably. The Society of Nuclear Medicine and Molecular Imaging, in their appropriate use criteria, just updated those to reflect the fact that, from their professional perspective, it doesn't matter whether you get a gallium-68-PSMA-11 or a DCFPyL [fluorinated PSMA-targeted PET imaging agent]. I believe the National Comprehensive Cancer Network [NCCN] might be looking at this right now. It might update and create some language there as well. From our perspective, it's really about increasing access for those patients who would qualify and benefit from this drug.

Alicia Morgans, MD, MPH: I know that that has definitely been something that as a community we've really been, I would say, maybe a little bit surprised about. Something that we've thought about is how we actually, as you said, get the drug to patients because some organizations are using the DCFPyL agent. As you also said, there are differences in the half-lives of these agents which may make that an easier agent for some community centers or some centers in general—community or academic, wherever they are—maybe easier to use. That’s really important, I think, and as you're thinking about this and getting this drug to patients, Tanya, where do you see it fitting into the landscape? Which, of course, has become a bit crowded and definitely complex in the last few years.

Tanya Dorff, MD: Absolutely. I think there are many unanswered questions. For instance, if this patient has a BRCA2 mutation, would it be better to go to olaparib or rucaparib, or would it be better to go with the lutetium-PSMA–targeted treatment? We simply don't know, so I think we have to look at access. Unfortunately, that often plays a role in which treatments are available to a patient in a form that's affordable. For this, depending on how many centers in a given locality are offering the lutetium-PSMA treatment, it might be that it's too far for a patient to travel, and a pill is easier. For other patients, they may not have prescription drug coverage and this might be the better choice. I think essentially we want our patients to access all potential therapies that could benefit them, and it's more a question of sequence, and it'll look different in different patients because of that. I think with the very favorable toxicity profile that Ulka just showed us and the fact that it's administered once every 6 weeks, which is relatively low intensity in terms of clinic appointments, this is a very attractive treatment for someone who's progressed after 1 AR [androgen receptor]-targeted agent and 1 taxane. Although certainly it can be used after additional lines of therapy since those patients were also represented in VISION.

Alicia Morgans, MD, MPH: Ulka, you're working in a big center and have a key leadership role in phase 1 where you're getting drugs to patients in situations that would be really complex for even non-phase 1 groups within your institution, perhaps. How do you see getting lutetium to patients in a consistent way with the multidisciplinary and the screening scale requirements? How do we make that happen?

Ulka Vaishampayan, MD: I think this is going to need a lot of collaboration and communication between the 2 departments that are doing it. Medical oncology, urology, and radiation oncology will typically be the referring base. At our center, it's nuclear medicine administering this. There are other centers where radiation oncology is doing it, but regardless of who is doing it, I think you need to establish a pattern of the patient referral and who is checking each of the criteria before giving the dose to the patient. Obviously, the typical way of arranging these logistics and collaborations is you have to have a good communication meeting and the workflow has to be well established, and that is going to be key here. At least in our center, we have decided that we will refer the patients to nuclear [medicine], but we will have to do the initial scan that will then decide if the patient is a candidate for lutetium-PSMA, and then the nuclear medicine folks will take over. We will still be involved in checking the blood work on the patient, because, obviously, you saw there are some cytopenia involved and some toxicities that you do have to evaluate the patient for. The good thing is the doses are 6 weeks apart, so scheduling is going to be easy, but it does need to be handled in a very meticulous fashion so patients don't fall through the cracks.

Alicia Morgans, MD, MPH: I agree with all of that and hope that we are working behind the scenes even before we have lutetium ready to be doled out—to really get all of that in place—and to identify who's going to monitor safety labs and who's going to potentially give antiemetics, should those be necessary. Who's going to support the patients in between cycles, too? All of this is something that we absolutely can do and we do in other settings, and just some planning and forethought will be really helpful and go a long way.

Transcript edited for clarity.