Kim Chi: Sure. Well, the PLUDO study randomized patients with metastatic castration-resistant prostate cancer, or I'm supposed to call it APMR (androgen pathway modulation–resistant prostate cancer) now.
Zachary Klaassen: Sure. Yes.
Kim Chi: And randomized patients that were progressing after an ARPI and randomized them to either receive PLUVICTO or lutetium-177-PSMA-617 or docetaxel at standard doses and schedules. And as we know, we don't often compare active drug against active drug nowadays. And really it was to try to understand how these two drugs compare to each other. We know PLUVICTO, lutetium-177-PSMA-617, works very well post-post chemotherapy. We also know it works very well early, early on in patients that don't need chemotherapy. But how does it do against chemotherapy for patients that are eligible for chemo? And from the primary analysis, which was looking at radiographic progression-free survival, there was no difference between getting lutetium-177-PSMA-617 and docetaxel. However, what surprised us was that there was an overall survival advantage for patients that were randomized to receive docetaxel first.
Zachary Klaassen: And what's interesting is the analysis presented at ASCO is looking a little more into those crossover data. So maybe just set that up for us in terms of the design, that analysis, and what you found in those results.
Kim Chi: Yeah. So it is part of a pre-planned analysis to understand what is the crossover, which is something we also don't typically do in our oncology trials, understanding crossover effects and subsequent treatments. But here, this is baked into the protocol allowing patients to crossover if they had radiographic progression, but we also made allowances for patients that had symptomatic progression without radiographic progression to crossover. And what was immediately apparent was that there was an imbalance in crossover. So roughly 40% of patients crossed over from lutetium to docetaxel, but 60% of patients crossed over from docetaxel to lutetium. So there was an imbalance. So there's two questions that arise from that. So number one is, "Well, why was there imbalance?" And then so we wanted to try to address that. And then also, what happened with the crossover? So first, let me address what happened with the crossover.
Essentially, for patients that received both treatments, the sequence didn't matter. Whether patients received lutetium followed by docetaxel or docetaxel followed by lutetium, radiographic progression-free survival two, rPFS-2 or the second progression was not different. So whether you measured that from the time of randomization through first progression to second progression or from the time of crossover, there was no difference. And similarly with overall survival, there was no difference. Now going back to the question of why there was this imbalance in crossover, we didn't collect that data. It's very hard to collect the data why somebody doesn't get a treatment. So what we tried to do is look at it in a different way. So at the time of radiographic progression, how are the patients doing? So we looked at their quality of life by the FACT-P and at the time of first radiographic progression, quality of life was actually in favor of the lutetium arm. And then when we looked at adverse events that patients were experiencing, they were basically similar across both arms. So patients weren't crossing over not because of worse quality of life or adverse events.
Zachary Klaassen: That's a great background of the results. We have PSMAfore, we have VISION, we have PR21. Does the initial analysis presented at ASCO this week change how we position Lutetium, whether pre or post-chemo? Is it still shared decision-making? What's your insight into the overall landscape now?
Kim Chi: I think part of it is regulatory. I mean, in the US lutetium is available in the pre chemotherapy setting, but in the rest of the world, or most of the rest of the world, it is not. So I think what this does is actually it lends comfort or confidence that regardless of the sequence that you're using it in, that you're going to get a benefit for our patients. But I think what it also emphasizes is we should be giving docetaxel as a benefit of our patients. Whether you give it pre lutetium or post lutetium, we really should think about being using docetaxel.
Zachary Klaassen: Yeah. That's a great summary. Anything we haven't hit on? Anything you want to wrap up with for our listeners?
Kim Chi: There's going to be a lot more coming out from PR21 and PLUDO.
Zachary Klaassen: Excellent.
Kim Chi: That includes looking at quantitative PSMA PET. Can we identify patients that really will benefit from lutetium or that should be getting chemotherapy instead? And then we have a whole bunch of ctDNA genomic correlatives that will be coming out as well. So stay tuned more from PLUDO in the next year.
Zachary Klaassen: Fantastic. Thank you, Dr. Chi, for your time.
Kim Chi: Thank you.