Alicia Morgans, MD, MPH, and Karim Fizazi, MD, PhD, on Prostate Cancer: Study Findings on Health-Related Quality of Life and Pain

Alicia: Thank you so much for being here with me, Karim. I'm really excited to talk about PSMA4 updates in quality of life as well as the overall survival data. Why don't we just start there? Tell me what was the overall survival finding for the hazard ratio for PSMA4 this time? Karim: This was the third interim analysis for overall survival, and for the first time, the hazard ratio is below one, which at the end of the day doesn't change much scientifically. Probably just below or just above one doesn't mean much, but for regulatory purposes, this is very important because the agencies, of course, want to make sure we're not arming patients by overall survival in the long term. So it's really good to see that for the first time, the hazard ratio goes the right way. Alicia: Absolutely, and especially because this study really is looking at the use of lutetium PSMA-617 in a pre-chemotherapy population in MCRPC, it's so critical that we think about timing and sequencing. Part of that is really understanding the quality of life and whether that's going to be better or worse than our other alternatives, things like chemotherapy, which this trial is also trying to answer. Karim: Absolutely. This is really what we presented here at ASCO. We knew already that the primary endpoint of oligotrophic progression-free survival, was clearly improved by the early use of lutetium PSMA versus the second AR pathway inhibitor in men with castration-resistant disease, who had failed already on AR pathway inhibitor. But the question is really, is this imaging-based parameter translating, if you will, into direct benefit to the patient, which at the end of the day, probably you and me want to know. And this is why we looked at quality of life and pain. And indeed when we looked at the FACT-P questionnaire, for example, we could demonstrate a better time to deterioration in quality of life, favoring the lutetium PSMA arm, with approximately a 40% reduction in the risk. Similarly, when you looked at deterioration in pain, we saw also a 30% reduction in the risk of pain deterioration, again favoring lutetium PSMA. So I think this is direct measure of clinical benefit to our patients. Alicia: Absolutely. And one of the things that I think was so important as you were pulling out these quality of life metrics is you were able to drill down into those specific areas, those specific domains. Can you share a little bit about those findings? Karim: Yeah, sure. So for quality of life, it was pretty much all domains were improved by lutetium PSMA, including physical well-being, functional well-being, emotional well-being, all of those being very important. The only one which is not changed is familial well-being. Obviously you need more than an IV injection to change your family well-being, but this is another story. Alicia: Yes, yes it is. Karim: And for pain, we looked at pain as a whole, so pain intensity, if you will, but also the impact of pain on normal life, so interference and also cancer-specific pain, which also was improved significantly. All of them were actually improved significantly, which really is measuring different domains that are so important to all patients clinically. Alicia: When I think about quality of life data, I always try to think of it in the context of the responsibilities of the patient as well as the adverse event profile, of course, that we measure as clinicians. How does this data help you contextualize things like cytopenias or the burden of having to stay away from children for a week? The things that are occurring during treatment with lutetium PSMA-617? Karim: I agree with you, that's key. And indeed, of course, we presented already the adverse events that we saw in the trial, but in this analysis, we really focused on adverse events that can impact negatively on quality your life. For example, if you take severe anemia, mostly requiring a transfusion, as you just said, you have to go to the hospital, you're tired and everything. We saw that in 6% in the control arm and in 6% in the experimental arm, really, same thing, fatigue as measured by doctors. So not anymore quality of life, measured by the patient, but still about 25% in each arm. So we're really, I think, providing better anti-cancer efficacy with minimal burden in terms of side effect that can impact negatively on quality of life of patients with this treatment. So I really believe that for patients who are not candidate for immediate chemotherapy with docetaxel, again, these patients were out and we made very clear in the consent form that docetaxel chemotherapy was a standard of care and that this was an option. But in some cases, we all recognize in case of an indolent progression, mildly symptomatic, et cetera, there is no necessarily emergency to start the chemotherapy. So for those patients who are not candidate for immediate chemotherapy, I'm now quite convinced that indeed lutetium PSMA is a great option rather than using the second AR pathway inhibitor, which typically doesn't really work. Alicia: Absolutely. And by patient's own report, they feel like they're getting better, their pain is reduced, their quality of life and all those domains is better. It's interesting, the social one, like you said, treatment of your cancer is not necessarily going to fix any of your family relationships, but one thing that is important, I think it didn't show a major deficit, which could occur when you have to stay away from your family or you have burdens. Because now you're not allowed to be near people who could be pregnant or children, but this did not happen. Karim: You're very right. And actually the trend was favorable. When you look at the Kaplan-Meier curves, they actually favor the experimental arm, even if a difference is not significant for that specific domain. Alicia: Absolutely. So from my perspective too, this is a really important study, obviously, and one that we wait for regulatory consideration and we'll see where things go. But ultimately, I really appreciate the time that you took to share this at the meeting and of course to share it with me today. Thank you. Karim: My pleasure. Thank you.