So I would argue it's in many respects has been understudied in the sense that there are very few major trials that are looking at it compared to existing standards of care. And I'm going to talk about two of those, that is PEACE-3 and DORA. I do think that radium has a really compelling rationale for prostate cancer and substituting radium for calcium in the formation of hydroxyapatite. This is in essence a hydroxyapatite-targeted therapy in which radium phosphate is laid down. It has an imaging theranostic biomarker for hydroxyapatite deposition that is a standard bone scan and has compelling rationale of now laying down multiple layers of radium phosphate in hydroxyapatite and then in animal model at least killing the osteoblast and the osteoclast, which are in essence the effector cells of the prostate cancer. It's not so much an anti-tumor agent. PSAs don't necessarily go down, but it is a highly effective anti-osteoblast and osteoclast killer. So PEACE-3 is the second phase-three radium trial to demonstrate an overall survival benefit. And I have the benefit of presenting just after Dr. Gallardo presented the data at ASCO GU that are the most mature to be presented to date. So this is a study of metastatic CRPC patients now known as APMR.
With bone metastases, these patients had no prior treatment with enza or radium, but they also primarily had no other treatment with ARPIs as well. So this was truly a first-line metastatic CRPC study. The randomization was one-to-one to enza and radium versus enza monotherapy. And the primary endpoint was rPFS. I do think that that was kind of a bold primary endpoint because rPFS by bone scintigraphy could just be altered by the drug because it is, in essence, poisoning osteoblasts and reducing the hydroxyapatite deposition. And that might be why rPFS is somewhat blunted as a result, but OS was a key secondary endpoint. And I think that is what was updated at ASCO GU and is really, really important and warrants some additional discussion. So here are the final rPFS results, as Dr. Gallardo presented with a hazard ratio of 0.71 and a modest absolute difference of 16.4 months versus 19.19 months. When you look at the overall survival data, these are really interesting. So first of all, if you were sort of a quick to jump to judgment kind of a person within the first 18 months of looking at the data, you would think that this would be a negative trial and indeed perhaps with a slight survival deficit for the experimental group.
But then at 18 months, the lines definitely cross and stay well apart with a hazard ratio of 0.76 and a 5.6 overall survival difference in terms of the median OS in absolute terms. Now this is really quite extraordinary. I mean, that's a really good survival readout of this combination. And in the subset analysis, it really looks like the only group that might not benefit would be the elderly, age 75 or greater, but the effect was seen overall of the pre-defined strata. So this was actually quite impressive and quite well tolerated really in terms of excess toxicity there was some more, as anticipated, increase in fracture rate, these patients did receive bone protection, so 5% versus 1.8%. There were 17 cases of osteonecrosis of the jaw, which one would expect with that bone protection. Anemia was in excess relative to the enza alone, neutropenia as well. But overall, this is really well-tolerated treatment. I'm just putting up here all other studies that occurred in this metastatic castration-resistant population in the first-line setting so that you could compare these overall survival results with those of, for example, PREVAIL. Now, PREVAIL, if you recall, was the original trial in the pre-chemotherapy setting in which enzalutamide was approved and it had a hazard ratio of 0.77 and it had an absolute overall survival difference of four months. Throw in some radium on top of enzalutamide, you again have a hazard ratio of 0.76, only this is in comparison to enza alone, and you've added another 5.6 months in terms of overall survival better than enza versus placebo.
So I think that this is really a remarkable combination. It would be great to see other combinations that are going to be discussed later in this conference that would have such good results as this combination in prolonging overall survival. You will see though what I was saying about rPFS, the difference between rPFS in PREVAIL of enza versus placebo was on the order of 20 months versus five months. So a hazard ratio there of 0.32 is 70% improvement. You did not see that with rPFS in PEACE-3. And I think that that's because of the mechanism of action of radium to some degree. We can talk about that during the discussion. Now, in terms of DORA, DORA is looking at radium versus docetaxel. So a dual compartment targeting strategy of targeting the antimicrotubule therapy with docetaxel versus the bone microenvironment with radium. This is not completed in terms of events, but it is completed in terms of accrual. This was a trial that did allow a certain amount of visceral disease and did allow some nodal disease because all patients were getting chemotherapy in this trial. So we felt that this was an ethical broadening of the eligibility criteria, but they did still need to be bone-dominant in order to be eligible for the trial.
The regimen was docetaxel at 60 milligrams per meter squared. That's a dose reduction for those of you who aren't oncologists. And radium given on an alternating interdigitated schedule. So it's doce and radium, then doce, then doce radium, then doce for a total of 10 cycles of doce and six cycles of radium. We did need to dose-reduce the docetaxel because in the phase 1-1B study, there was an excessive neutropenic fever with doce at its standard dose. The control arm is docetaxel at 75 milligrams per meter squared for 10 doses, that's standard. And the primary endpoint for DORA is overall survival with secondary endpoints of rPFS, SSEFS, ALP progression, quality of life, and others. I do want to thank what is in essence a huge international collaboration for what is ultimately an academic study, although we've received a lot of generous funding for this study from Bayer. It is an IIT, and these are sites in the US, in Brazil, in Spain, and then in the Netherlands who have really contributed to this throughout the shutdown for the pandemic internationally, the study continued to accrual. We didn't have to make some pragmatic changes in order to let patients get chemotherapy on the control arm, for example, at their local oncologists instead of necessarily traveling to a cancer center. But we did finish the study, and it is now completed in terms of accrual, and we anticipate that at the event rate that we project that we should be done by the end of the year and have a result.
So in conclusion, I would say that radium-223 should not be forgotten as a means of addressing the prostate cancer bone microenvironment using a theranostic approach, even though the shiny penny today is tumor-directed strategies with PSMA or others. The combination with ARPI in especially first-line metastatic CRPC, which is what this trial really focused on in terms of P3, yields an OS advantage that really is not seen in any other prostate cancer study in terms of its absolute number of months of benefit as a median and combination with chemotherapy with DORA should yield a result sometime in late 2026. Thanks very much.