Recent Advances in the Treatment of Prostate Cancer - Episode 15

Role of 177Lu-PSMA-617 in mCRPC and Bone Metastases

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Shifting their focus to 177Lu-PSMA-617 in metastatic CRPC, expert panelists consider its role in sequencing therapy and managing bone metastases.


Alicia Morgans, MD, MPH: To switch gears one more time, I’d love to hear from your perspective, Sandy, about lutetium PSMA [prostate-specific membrane antigen]-617, which is a treatment we’ve been talking about a bit in terms of identifying patients using a PSMA PET [positron emission tomography] scan. We’ve heard allusions to it, but can you explain where this particular treatment sits in the available landscape for patients getting treatment for metastatic CRPC [castration-resistant prostate cancer]?

Sandy Srinivas, MD: All of this is going to be based on the VISION trial, and the selection of patients for the trial were those who had prior AR [androgen receptor]-targeted therapy and also prior taxane-based chemotherapy, 1 to 2 [regimens]. When lutetium-177 becomes available to us, I suspect it will be used in that exact scenario: patients who have had prior AR-targeted therapy and prior chemotherapy. Selection will probably be based on the PSMA scan. One thing that we haven’t spoken about is the availability and access to this. I think that much of this is dependent on where patients are, where the availability of these imaging modalities are, and also where in this space we’ll be able to use it according to payer approval. I think once it becomes available, I see it being used in patients more with advanced disease who have had all prior therapies, including our much-available AR-targeted drugs and chemotherapy.

Alicia Morgans, MD, MPH: I think that makes sense given that’s the area where it was studied. Certainly there are multiple trials going on, and we would all encourage clinicians and patients to engage in those trials if they’re the right thing for that individual patient so that we can continue to answer some of these questions. Just thinking about the heterogeneity again of the patients who are suffering from metastatic CRPC, Scott, how do you think about the patient population that specifically has more of a bone-predominant metastatic spread, perhaps a patient population that has some pain in those areas? What are you thinking about in terms of treatment for those patients, and how does lutetium PSMA-617 come into that decision-making?

Scott T. Tagawa, MD, MS, FACP: Bone is clearly an important site of disease for many patients with advanced prostate cancer, and is important as a site of morbidity. For instance, pain can be from a tumor, it can be from a tumor leading to a fracture, or a fragility fracture because of either age and/or prior, especially hormonal, therapy. So, bone is an important site overall, and I think it’s important to remember bone health and bone health agents, so for osteoporosis treatment and/or prevention, even in the setting without metastasis, and then at least for castration-resistant metastasis, the bone health agents for risk reduction for skeletal or symptomatic skeletal events. We also can directly treat metastasis. For a very long time, we’ve given external beam radiotherapy, palliative in nature, to certain areas. I use that in particular when there is 1 dominant area that’s causing a lot of pain and there may be less in other areas. We have bone-seeking radionuclides in terms of radium-223 hitting hydroxyapatites, where we know there’s actually not just an improvement in symptoms, such as with strontium or samarium, but we can improve those symptoms and survival with radium, with lutetium PSMA-617.

Probably other PSMA-targeted drugs, if we have other ones that are effective, will go to at least tumors in bone, because most disease sites of prostate cancer do express PSMA, but also target other areas. So, if I were worried about a patient who had a significant amount of symptomatic bone metastases but also a significant disease outside of the bone, then maybe radium wouldn’t be the best choice unless I was through every other kind of option. But maybe something like lutetium PSMA-617 would be a good choice in that particular situation. We do know that these drugs can be used sequentially, so in many of the studies, including VISION, patients had radium-223. Others had them in the reverse order, so it is possible to do both.

Alicia Morgans, MD, MPH: That makes sense. I think it’s always important to think about strategies now but also what opportunities and options we’re going to have in the future and how each treatment decision might affect the one we have next. Thank you for those comments.

Transcript edited for clarity.