Michael Morris, MD

Tanya Dorff, MD

Evan Yu, MD

Rana McKay, MD

GU Oncology Now

A roundtable discussion, moderated by Michael Morris, MD, discussed the current landscape of radioligand therapy in prostate cancer, including recent trial highlights presented at ESMO 2023. Dr. Morris was joined by Tanya Dorff, MD; Evan Yu, MD; and Rana McKay, MD.In the next segment of the roundtable series, the panel talks &ldquo;pearls of wisdom&rdquo; with radioligand therapy, including dose modifications, adverse events, concurrent ARSI use, and more.<a href="https://guoncologynow.com/post/prostate-cancer-panel-reacts-to-psmafore-study-presented-at-esmo-2023">Watch the next segment in this series.</a>&mdash;Dr. Morris: Could each of you give the audience maybe 1 pearl of wisdom on the standard use of radioligand therapy, especially for lutetium PSMA-617 that we haven&rsquo;t covered yet? Tanya?Dr. Dorff: I just want to emphasize, because I think it&rsquo;s not widely known, that you can use a different dose. I think because of radium, perhaps, where there wasn&rsquo;t really a dose modification, it just wasn&rsquo;t so apparent. If I have a patient who&rsquo;s really struggling with cytopenias, I will do a dose reduction. Just want that to be out there.Dr. Morris: Excellent point. Evan?Dr. Yu: We haven&rsquo;t talked about adverse events. I&rsquo;m going to focus on a unique adverse event that we don&rsquo;t see a lot in oncology other than maybe head and neck tumors where they get radiation. But xerostomia is something that can occur with these patients because PSMA is highly expressed in the salivary glands. I always spend a lot of time counseling the patient in advance about things to avoid, things to do. I tell them, if you&rsquo;re smoking, quit smoking, it dries you out. If you drink a reasonable amount of alcohol, cut that back or down because that dries you out as well. Avoid alcohol-containing mouth washes. I give them tips on xylitol gum, these sorts of things. We want to avoid the use of artificial saliva because let&rsquo;s be really honest, nobody likes that. It&rsquo;s kind of gross, but it&rsquo;s there as an option.Last year, there was an interesting abstract and it was applied to head and neck cancer radiation using acupuncture. It was a randomized controlled trial where they did sham acupuncture sites. I was really intrigued by that, but it seemed to be very beneficial. I don&rsquo;t know that it could be applied in this situation, but it&rsquo;s something to think about. I think that moving forward, we need to work harder to think about how we can address the xerostomia that occurs, dry mouth that occurs, whether that&rsquo;s with supportive care, whether that&rsquo;s with different compounds. I&rsquo;ve even heard that people have tried working with oral surgery or dentists to inject cold radiotracer in the salivary glands, but it&rsquo;s an area that we need to focus on for quality of life for our patients.Dr. Morris: So glad that you brought this issue up. First, in terms of adverse event management, second, in terms of specifically the xerostomia, because it does happen and although it&rsquo;s generally low grade, it does bother patients, and it is an area where I think as GU oncologists, we are not equipped with the management skills or even with the research skills to manage these patients without collaborating with the dental community, with the head and neck community. We can learn not just the acute management, but also start clinical trials on better ways to prevent xerostomia, especially as we move into the era of the alphas, which I think is a whole area of investigation that&rsquo;s now dawning where the xerostomia is really dose-limiting.That&rsquo;s a very good point. I&rsquo;m really glad that you brought that up. It is dose-limiting in some of our patients, even with lutetium, and I think that I feel really uncomfortable that I don&rsquo;t have mastery of this. I do call my head and neck and dental colleagues to figure out ways to manage it, and the nursing community for the head and neck patients is really a resource of ample knowledge on managing xerostomia.Dr. Yu: I mean, 1 thing I&rsquo;m curious about are patients that have lower volume of disease. Do they actually have more xerostomia? Or as you treat the disease and you have less and less PSMA expression, like most things do you get diminishing law of returns over time?Dr. Morris:&nbsp; Yeah, I think that there are, but if you look at the VISION trial, the greatest predictor of xerostomia is preexisting xerostomia. Especially for the patient who comes in complaining of dry mouth, it&rsquo;s a patient that really will need some oversight and careful monitoring. We also don&rsquo;t query xerostomia particularly carefully. We don&rsquo;t really talk about, with patients, in most therapies that we administer, like how lubricated your mouth is and how is food going down and how is chewing? That&rsquo;s not something that we generally discuss. I think for this therapy, it&rsquo;s really something that is worth querying and taking a more thorough history than we usually do. What&rsquo;s also been suggested for future clinical trials is perhaps assessing salivary gland flow, because flow, according to the dental community, will slow down before symptomatic xerostomia. You might have a predictor if this is built into clinical trials, so that you don&rsquo;t get to the point of actually becoming symptomatic. Very good. Rana, what&rsquo;s your pearl of wisdom or point that you&rsquo;d like to highlight that we haven&rsquo;t discussed?Dr. McKay: Maybe the other point to discuss is in the VISION trial, patients who received a lutetium PSMA were also largely getting concurrent standard of care. Over 80% of patients were getting a concurrent ARSI [androgen receptor signaling inhibitor]. I do think, in my practice, when I&rsquo;m using lutetium, I am taking that into consideration when I am using, for example, if somebody has been previously treated with abiraterone, they haven&rsquo;t seen an AR antagonist, we do know that there&rsquo;s cross resistance. I would never really consider using the AR antagonist alone, but potentially to optimize their opportunity of enhanced response to lutetium combining the 2 together. I tend to try to combine if feasible and I&rsquo;m not going to worsen toxicity for that given patient.Dr. Morris: Tanya, what do you do in practice? Do you usually give lutetium alone, or do you give it with another agent?Dr. Dorff: If they&rsquo;re on an ARSI, I&rsquo;ll continue it, but I don&rsquo;t really usually go out of my way to add one.Dr. Morris: How about you, Evan?Dr. Yu: Similar to Tanya.Dr. Morris:&nbsp;I think that it&rsquo;s an interesting question, because although generally, we wouldn&rsquo;t favor putting patients on a secondary ARSI, even in PSMAfore, which we&rsquo;re going to talk about in a moment, you had a 20% to 30% PSA [prostate-specific antigen] decline in the control arm, which would suggest that some patients are still having a functional AR, and perhaps then you do get a little bump in PSMA expression by putting that on in some patients. If you look at the subgroups of the patients in VISION, those who seem to have done the best are those who are on another ARSI. Maybe what you could see from ENZA-p and maybe what you could see from the subset analysis of VISION, there is something there that even though the current label is for patients that have fairly extensive treatment histories and ARSI switch with Pluvicto might be worth the try given the potential gain and probably minimal downside of doing so. It&rsquo;s something that I&rsquo;ve thought about, and I think every patient, you try and tailor that potential for a combination individually, but I think there may be something there.