Chapters Transcript Video 2026 ASCO Prostate Cancer Highlights The Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute presents a succinct summary of all the prostate cancer clinical updates. So first up, we have um updates from the ASCO annual meeting 2026 for prostate cancer. I'll be discussing a number of abstracts and Doctor Choudhury will provide his expert commentary. So first up, we have the Proteus study, um, and Proteus, uh, I think builds on an emerging evidence that we know for patients with high risk localized prostate cancer, they have a high risk of recurrence of disease and at least currently our standard of care is radical prostatectomy alone versus EDT plus radiation and um there has been a number of studies led by Doctor Ka. And, and many folks at Dana-Farber investigating whether or not neoadjuvant hormone therapy prior to prostatectomy can improve outcomes, and I think a lot of it is based on, you know, evidence that we know whether patients have surgery or radiation plus hormones, the rates of um of recurrence are somewhat high. So you see the, um, this is a real-world registry. Um, in Europe where we saw that, um, the rate of BCR-free survival with surgery alone was about 50% and 80% with radiation. Um, so clearly an unmet need here to try to improve outcomes for our patients with high risk localized prostate cancer, and this was previous studies again led by Mary Ellen Taplin here at Dana-Farber showing that um neoadjugent 8. plus abiraterone did lead to modest improvements in pathologic response rate and probably more impressive, um, decreases in residual cancer burden at the time of prostatectomy. And you know, I think there's all the rationale in the world here. If our standard of care for patients with metastatic prostate cancer is ADT plus ARPI, then it serves to Ask the right question of does this approach also um uh improve outcomes prior to surgery. And so that was the idea behind the Proteus study. This was a large randomized phase three trial, um, that enrolled 2100 patients um with high-risk localized prostate cancer to perioperative ADT plus appalutamide prior to, uh, prostatectomy, followed by ADT plus appalutamide or placebo. The primary endpoints of the study were #1, looking at pathologic response rates, and #2, looking at metastasis-free survival. I will note when the study was first launched, the primary endpoint was looking at MFS by conventional imaging, so CT and bone scan, and then as PSMA PET became more standard practice, it amended that primary endpoint to be uh MFS by both conventional imaging and PSMA PET imaging. As the study, um, went on. So this was again a huge, huge effort, um, by, um, folks all over the globe to enroll to this study, um, throughout the pandemic. So, This, um, this was a high-risk patient population, so we know that, um, over 95% of patients, um, had Gleason 8 or higher. The baseline PSA was, um, it was greater than 20 in 40% of patients, um, about a third of patients had T3 or higher disease, and about 12% of patients had clinically node positive disease. We know Proteus met both primary endpoints, um, with an improvement in uh pathologic response. Um, you see on the left-hand side, ADT plus appalutamide had a pathologic response rate of about 9% relative to ADT plus placebo of 1%, and then in an exploratory endpoint of residual cancer burden, we see that ADT alutamide had a 30% rate versus just 10% with ADT and placebo. The second co-primary endpoint, we saw an improvement in MFS by conventional or PSMA PET imaging with a hazard ratio of 0.80 that was statistically significant, translating to a 20% reduction in the risk of metastasis metastasis or death after one year of perioperative ADT plus alutamide. This study showed a remarkable number of secondary endpoints, uh, showing that ADT plus appalutamide improved event-free survival, time to subsequent therapy, time to distant metastasis, and importantly, time to um requirement of post-operative radiation where you see about a 5% difference between the ADT plus alutamide relative to ADT alone. Um, interestingly, uh, we saw similar rates of testosterone recovery in the, uh, ADT plus apalutamide and ADT alone arm, although the time, um, to, uh, testosterone recovery was about 8.1 months with the combination versus 6.6 months with ADT alone. Um, there were higher rates of treatment-related adverse events at, um, a grade 34 treatment-related adverse event rate of 27% with the combination relative to 19% with ADT alone. We know, um, alutamide does have a skin rash as the most common adverse event, but also lower rates of, um, things like fatigue and seizures with the addition of aalutamide relative to, uh, ADT alone. So, Again, our takeaways are that, you know, this study did meet both primary endpoints, improving PTCR and MFS rates. It did come with a slight increase in treatment-related adverse events with the combination. Two common critiques that we heard discussed, um, ad nauseam at the meeting and then on social media were that, um, you know, um, this study did not use, um, you know, radical prostatectomy or radiation plus hormone. As a standard of care in the control arm, um, and you know, I think the responses to that are, well, we needed to have a blinded trial, and if you enrolled this patient and they went right to radical, um, prostatectomy, um, then they may drop out of the study and we wouldn't be able to interpret any of the results of the study. Um, the second is that, um, there is a complementary sub-study being done comparing the results of Proteus to an RP alone, um, uh, cohort of patients. So hopefully we'll have more data to help guide, um, how this compares to what we would consider standard of care in high-risk localized prostate cancer. Again, we did mention at the beginning that the, um, composite endpoint, um, did include PSA PET and conventional imaging. Um, and, um, we, when they break down the hazard ratio by, um, the composite versus PSMA pet alone, you see those hazard ratios are actually quite close together. And so, um, to me, I, I think this is, um, you know, a really robust study that has the potential to really change care for many of our patients with high-risk localized prostate cancer. Um, I still think that this requires very careful discussion in our multidisciplinary. And so I think it's, um, something to be considered, and obviously we'll have to wait for uh regulatory approval to see, um, what the FDA and others, um, decide in this space. And then also worth asking the question, well, who are those patients who may benefit most from perioperative therapy? Is there an opportunity to potentially de-escalate therapy who have in patients who have a robust response. Therapy, and I really like the discussion, uh, Doctor Declan Murphy, um, kind of broke it down this way. He said, those patients who are opting for surgery, um, and have an unfavorable prognosis or who have a favorable prognosis may be able to go straight to surgery, but those with intermediate or porous disease, you could consider giving this neoadjuvant ADT plus. Uh, have the radical prostatectomy, and then those patients who have a path CR or no residual cancer burden, perhaps those are patients who don't need the adjuvant therapy, whereas those patients who don't have a robust response, um, the 90% of patients who don't have a robust response, maybe those are the folks who really do benefit from the incorporation of that adjuvant ADT plus alutamide. Um, so again, I, I, I think a, a, a remarkable study and one that I think, um, it's gonna take many, many, um, months and years to try to understand how do we incorporate this into our clinical practice. Um, the next study that we'll talk about is, um, in the metastatic castrate sensitive prostate cancer setting. This is the Talaro 3 study, and Um, again, I think it's worth, um, this is a slide that we've brought up in previous iterations of these conference highlights, and we're thinking about, well, you know, PARP inhibitors, we initially got them, um, approved as monotherapy and castrate resistant prostate cancer, then they migrated in combination for first-line metastatic castrate resistant prostate cancer, and now we do have an approval for nerarib plus abiraterone in the castrate sensitive. Prostate cancer setting, although only for patients with BRCA2 mutations, and so it's into this space that the Talaro 3 results land, and this was, um, again, also a large randomized phase 3 clinical trial, um, which enrolled patients with, um, HRR altered, uh, castrate sensitive prostate cancer, of which the HRR genes are listed in red. I will note that this And this study did allow prior dose, this study did not allow prior docetaxel and used stratification factors of de novo versus relapse disease, high versus low volume, and BRCA versus non-BRCCA mutated disease. It randomized patients to either the combination of Talazaa plus enzalutamide or enzalutamide plus placebo with the primary endpoint of radiographic progression-free survival. And, um, this was a pretty high-risk patient population, so we see about a third of patients had BRCA1, BRCA2 mutations, over 80% of patients had de novo metastatic disease, 70% of patients had high volume disease, and over 80% of patients had Gleason 8 or higher disease. Um, when we look at the individual HRR mutations, again, about a third of patients had BRCA1, BRCA2, but 30% of patients had ATM. Again, this is probably one of the largest um prospective studies using a patient for patients with ATM mutations, and then about 20% of patients had CDK 12 mutations. Telpro 3 met its primary endpoint with an improvement in radiographic progression-free survival with a hazard ratio of 0.48, with a median that has not been reached in the intervention arm. When they broke down, uh, the subgroups of BRCA versus non-BRCCA, um, you see that patients with BRCA1, BRCA2, the hazard ratio is even lower, 0.36, and the non-BRCCA was 0.56. Again, both statistically significant results. When they looked at the forest plot by individual genes, you see again small numbers, but perhaps a benefit seen in of the combination seen in patients with ATM mutations and CDK-12 mutations in addition to BRCA2. Um, at the time of this interim analysis, the overall survival, um, was, uh, not improved, although trending towards an improvement with the hazard ratio of 0.76 in medians that have not yet been met. Again, median, um, uh, median follow-up on the study was about 40 months. Um, the combination talazapeib did have higher rates of uh grade 34 adverse events, so you see 79% relative to 41%. And then, um, higher rates of dose reduction at 60% versus 7 and discontinuation at 19% versus 10%. The, um, common adverse events we saw, by far the most common was anemia, but also fatigue, other cytopenias, um, GI adverse effects, um, commonly at grade 1, grade 2 relative to placebo, um, and then adverse events of special interest, um, there were 3 patients who developed MDS while on Talisapra plus enzalutamide and 2 patients who had AML, um, on the combination relative to no patients who were on placebo plus enzalutamide. Um, they did have a slide about the anemia, and they found that, um, the anemia was often an early phenomenon, and that at baseline, 43% of patients had grade 12 anemia, the median time to grade 34 anemia was 3.2 months, and 40% of patients actually had to get a blood transfusion with a median of 2 transfusions. Infusions over the duration of therapy. Um, they did say that, you know, in order to remain on protocol, patients had to have their anemia, um, treated and resolved quickly, and so that may have driven more folks to give transfusions than they might have otherwise, but still anemia stands out as a significant adverse effect of taissaarib. So, again, the takeaways from the study, Talisaib plus enzalidide improved RPFS, however, OS remains immature at this time. The most impressive benefit, as we've seen across all of these studies, is in the BRCA1, BRCA2 mutation carriers. Although I'll argue that the non-BRCCA, um, this is probably one of the more impressive data sets in the non-BRCAHRR with a hazard ratio of 0.56 for RPFS, um, that did come at a cost of increased risk. Of hematologic hematologic adverse effects, and at least at this early end point there were again 5 patients who developed either A AML or MDS while treated on this study. So I think it'll be, you know, really important to continue to follow this study over time to see if some of those chronic chronic hematologic toxicities. Um, worsen over time, and then also thinking about this is a positive phase 3 trials um published in the New England Journal of Medicine, is there an opportunity that Tazaper plus enzalutamide will be approved for patients with all HR mutations relative to the current label that we have for the rapi plus abiraterone only in patients with BRCA2. And then also worth stepping back and say, well, you know, if this triplet is is um approved, how do we compare it? We obviously have no head to head data, um, comparing it to other currently approved triplets of docetaxel, um, or Capipizertib, which was just FDA approved for patients with P10 deficient, um, castrate sensitive prostate cancer. So obviously a lot of, um, uh, fantastic result, but a lot of ongoing questions as to how we're going to incorporate this into our rout. practice. Um, there are several other studies that are currently ongoing, um, for PARP inhibitors in the castrate sensitive prostate cancer setting, as well as in the high-risk localized setting. So it's possible we may see PARP inhibitors move even earlier in the disease setting. Obviously, again, trying to, um, use biology to, um, to, you know, provide therapies that we think are more directed at the biology that's driving, um, this disease, um, rather than taking a one size fits all approach. Um, I, we do have a study open at the Talent study here at Dana-Farber. This is led by our own Alicia Morgans, um, which is investigating for patients who have ADT plus ARPI and have a HRR mutation, um, and it's investigating whether or not we should, uh, be continuing the ARPI after progression in combination with talisopaib or just moving on to giving PARP inhibitor as a monotherapy alone. Um, last is, uh, the last theme that we'll talk about is optimizing the patient experience for patients with advanced prostate cancer, and this is 3 studies, 2 of which were led by our own investigators here at Dana-Farber. Um, the first is the ADREAM study. This was a cooperative group study again led by Doctor Atish Shoudhury, which was investigating, um, um, actually de-intensification of therapy for patients, patients who have an exceptional response to ADT plus ARPIs and metastatic prostate cancer, and Um, again, the data that we often cite of the intermittent versus continuous approach was based on trials that were launched and reported over 10 years ago, where we didn't have ARPIs available to us, and we, you know, had, um, PSMA, we had PSA but we didn't have PSMA PET scans, so I think, you know, certainly. Worthwhile asking that question again of, for patients who have an exceptional response to therapy, where we know their PSA gets to less than 0.2, we know the overall prognosis for those patients is rather good, and so can we, um, you know, um, trial those patients off of therapy and, um, and improve their outcomes. And so this was a very practical design. It was for all patients with metastatic castrate sensitive prostate cancer who had been treated with an ADT plus ARPI combination and had a PSA of less than 0.2 after 18 to 24 months of ADT. And, um, at that point, they would stop therapy, and they would have uh PSA and testosterone checks every 3 months, scans at least every 6 months, and quality of life assessments every 6 months. There were certain triggers, um, that would trigger reinitiation of therapy, that would be if the PSA rose above 5, if there was radiographic progression of disease, or if patients had a prostate cancer-related symptom. And the primary endpoint of the study looked at treatment-free, um, uh, treatment-free interval, um, at 18 months with Egenal testosterone, which was in this study defined as having a testosterone above 150, again explored a number of secondary endpoints as well. Um, so patients who enrolled on a dream, um, I would say, um, they, um, had, again, um, um, metastatic prostate cancer, about 1/3 of patients, um, had high volume disease, about 40% of patients actually had no local therapy to the prostate, um, and about 30% of patients actually had radiation to metastatic sites. And a dream did meet its primary endpoint with an improvement in um in uh the treatment-free, the number of patients who are treatment-free at 18 months with testosterone recovery was 41%. Um, at, uh, 26.9 months of median follow-up, about 40% of patients actually restarted their, uh, 40% of patients were, um, continuing on the treatment interruption, and the other patients, um, had to resume therapy. And what we saw was the median time that patients were off therapy was 24. 5 months, and the forest plot looking at factors that were associated with the necessity to restart treatment were patients who had a higher volume disease or patients who had not had radiation to metastatic sites. Put another way, patients who had low volume disease and had radiation to metastatic sites were less likely to require reinitiation of their therapy. When we look at radiographic free and overall, uh, radiographic PFS and OS again, relatively low rates of uh progression and uh really outstanding overall survival was seen in the 75 patients. Um, I will say 4 of the 29 patients who had to restart ADT plus ARPI had later progression, um, and, um, And only one patient on the study, um, actually had, um, death related to prostate cancer, and that was due to a neuroendocrine conversion. So I think Some of the takeaways that we have are that treatment interruption for patients who have an exceptional response to ADT plus ARPI led to a 40% treatment-free interval with a recovered testosterone at 18 months. The median time off therapy was 24 months, and factors associated with remaining off were patients who had low volume and prior radiation. Um, and I think again this um confirms what, what we suspected from a lot of the retrospective studies, but now provides prospective data, um, telling us that, um, a de-intensification approach is feasible for patients with metastatic prostate cancer. And I will call attention to a um a larger study now being run in the ARRTC which is investigating treatment de-intensification again for patients who have an exceptional response to upfront ADT plus ARPI therapy. Um, the next study that we'll talk about is the ERCOG study. This was a phase two trial, led by our own Alicia Morgans, which examined the cognitive adverse effects of dalutamide, one of our ARPIs versus enzalutamide, and again, mechanistically, I think one of the differences that we've known about for a while is that dalutamide does not cross the blood-brain barrier and thereby is hypothesized to have less CNS and less cognitive effects than we see. With enzalutamide, and so this is a, you know, prospective phase two study, um, evaluating what some of those cognitive changes are with one versus the other. Um, this study evaluated patients with, um, who had an indication for ADT plus ARPI therapy, whether that was with a metastatic castrate sensitive prostate cancer, non-metastatic castrate resistant prostate cancer, or castrate resistant prostate cancer, and it randomized patients in 1 to 1 fashion to Daalidomide, which was provided by the um study sponsor, or enzalidomide, which was obtained by um by standard of care, and then as you see at weeks 0, 1224, and 48, um, patients uh did cognitive testing through several validated measures, and they also reported patient reported outcomes and did something called a Tug tests at each of these twelve-week intervals, and then, uh, there were certain criteria by which if patients had a decrease in any of these, they were eligible to cross over either from ENZA to Darow or Darow to ENZA. Um, I'm not gonna go too far into the, uh, outcome measures because it's very complex, but, um, just know that these are, um, validated, um, uh, patient reported outcomes and cognitive tests that, um, patients and investigators were trained on, and, um, had a high level of, of, um, Of completion during the study. Um, when we look at the patient characteristics who enrolled on the study, we see about half the patients had castrate sensitive prostate cancer, maybe about 30, 40% had castrate resistant disease, and less than 10% had, um, non-metastatic castrate resistant disease. And the primary outcome of the EIO study showed an improvement in the cognitive decline with dalutamide relative to enzalutamide, so we saw a 16% decrease in cognitive decline with dalutamide relative to 36% decrease with enzalutamide with a significant P value of 0.09. And at 24 weeks, 4 out of the 5 modules were statistically significant, um, statistically different between the arms, favoring the dalutamide over the enzalutamide. And interestingly, um, when they looked at patients who were eligible for a crossover, we saw a much higher rate of crossover from enzalutamide to dalutamide. We actually saw 0 patients crossover from the dalutamide to enzalutamide. And so, what are some of our takeaways? I think it tells us that, you know, patients with advanced prostate cancer, um, had a greater cognitive decline with Enza versus dalutamide. Um, I will say that there are some limitations of this as a small phase two study, it was an open label design, and so there may be some biases associated with that, but I think broadly speaking, you know, um, patient reported outcomes we know are important, and, um, this study, I think among others, can, um, help inform our choice of which ARPI are we choosing for our patients with advanced prostate cancer. And the last study that we'll go through is, um, is a study out of Switzerland. This was actually a phase 3 non-inferiority study, looking at the uh reduced dose of denosumab, either given every 12 weeks or every 6 weeks. It was called the Reduce study. And as we know for our patients with metastatic prostate cancer with bone metastases, um, we know that there are indications for, uh, bone protective agents with denosumab and, uh, zoledronic acid. And again, the reduced study, this took patients either with castrate resistant prostate cancer or metastatic breast cancer, and on the standard of care RMA during the induction phase, patients would get uh denosumab every 4 weeks and then continue. Uh, as a in a maintenance approach, giving the drug every 4 weeks, but in the intervention arm, um, after that induction phase, patients would then go on to get denosumab every 12 weeks, and the primary endpoint was looking at time to first uh symptomatic skeletal event. As mentioned, this study did include about 60% of patients with breast cancer, 40% of patients with prostate cancer, and impressively, about 55, 60% of patients had more than 10 bone lesions at baseline between the two arms. Um, this, uh, reduced study did meet its primary endpoint, and it showed non-inferiority between the Q4 week and the Q12 week dosing, with a hazard ratio of 1.0 and a median follow-up of 37 months. Secondary endpoints also showed that less of uh uh, no difference in time to first or subsequent skeletal symptomatic skeletal related events and lower rates of hypocalcemia, lower rates of osteonecrosis of the jaw or tooth infection, all favoring the Q12 week dosing to the Q4 week dosing. Perhaps most impressively, the Q4 week dosing, uh, the Q12 week dosing was associated with a cost savings of about 50%, um, with a difference of about $10,000 US dollars in the Q3, the Q12 week dosing versus the Q 4 week dosing. So what are some of our takeaways? Again, I think it shows that the denosumab Q 12 week dosing was not inferior to Q4 week for a time to first symptomatic skeletal event in both metastatic breast cancer and Uh, metastatic castrate resistant prostate cancer, the Q12 week again had lower rates of adverse events, significant cost savings. I will say they didn't give us any analysis of the breast cancer versus the prostate cancer, um, populations, but it'd be interesting to see once the data is published, if, if we do see a difference between those two, in my practice, I would see this as, you know, a good option for the prevention of ske symptomatic skeletal events and Again, you know, um, not requiring patients to come in for a monthly injection of denosumab, I think is a fantastic outcome to expand on. So, um, with that, I'll pause and invite Doctor Atti Choudhury for his commentary. Um, thanks so much, Mike, for going through all this data. Uh, I would say that these are very challenging studies to discuss in a, um, as an individual, like, it's really about discussion because many trials that are done and performed change standard of care, and these, um, also change standard of care, but also introduce complexity, um, in a lot of our clinical decisions. So as you note, the Proteus trial was a um giant international endeavor, a huge trial, um, where uh this is the largest perioperative trial in prostate cancer, and the trial did meet its primary outcomes of the, um, Of the uh complete response as well as MFS, but again, as you mentioned, the MFS was a composite of, uh, the conventional and PSMA PET based MFS, and there's no OS difference to date. So, I think the lens around which we should view Proteus is, um, really needs to be patient-centered and patient specific about what are the, um, Potential benefits of this sort of approach, and what are the potential downsides of this sort of approach, um, rather than being dogmatic around, um, endpoints and, uh, and control arms, etc. because it does compare to a control arm. A perioperative ADT alone, which is not standard, but the blinding does allow us to be quite confident that some of the biological effects that we're seeing are, um, are real and associated with the drug, especially the delay to, um, In terms of events and in terms of next treatments. So, I would say that based on this study, if we have a patient who meets these eligibility criteria, which did require um fairly high volume of high risk disease, um, you couldn't get on with just a couple courses of Gleason 8, for example, um, that this introduces uh an option of perioperative ADT alalutamide, um, both neoadjuvant and adjuvant, compared to doing surgery followed by Uh, salvage or adjuvant radiation if needed, versus ADT and um plus or minus an ARPI with radiation, depending on the degree of their disease. And all three of those approaches have risks and benefits that are associated with it, and certainly a perioperative approach, uh, with ADT does have some, uh, introduced some challenges in that it makes it difficult to interpret the pathology at the time of surgery in terms of what the pre-treatment. Um, disease involvement was, it makes it difficult to interpret the, um, postoperative PSA as you, um, noted, 80% of patients recovered their testosterone to greater than 200, but that left almost, um, 1. With the patients who did not. So, there are some, um, downsides of this approach, um, especially if there's an option of, um, getting upfront surgery and saving the toxicity and side effects for, of ADT. Um, for later on whenever needed with salvage radiation. So I think clearly in patients who have a contraindication to radiation, um, poorly controlled Crohn's disease, or they had prior radiation to the area, um, the findings from this trial definitely support using perioperative management, um, to, uh, avoid radiation for primary treatment and decrease the need for salvage radiation. In patients with um high volume disease where they have reasons for prostatectomy for other reasons, um, whether it's a big symptom burden for urinary obstruction, whether it's because they're young and healthy, and they have a long time to develop local recurrences within the prostate, it's, it's really a discussion about risks and benefits, understanding what the other options in this particular setting are. And Doctor D'Amico noted that it was interesting, um, that the drop in need for post-op radiation was actually less than 10%, um, though it did delay the time to radiation by about 3 years, and that delay in time to radiation, um, could be clinically meaningful, especially for patients who have, um, issues like, um, ulcerative colitis, Crohn's disease, something that might need to take time to recover or resolve before you might do the radiation. Um, the Taopro 3 trial similarly, uh, was quite positive a trial in terms of RPFS and the overall survival also trended towards improvement as well. But as, uh, I mentioned earlier for Proteus, it does introduce complications because in Talipro 3, the rate of crossover, um, to receive a PARP inhibitor in the control arm was something like 27%. And so it doesn't really answer the question about what is the true benefit of giving a PARP inhibitor upfront compared to, let's say, waiting at first progression to CRPC and how does that play out in terms of overall survival, um, patient outcomes, uh, symptoms, etc. Because the problem with upfront talisariibin and salutamide is that it does have Negative impacts on quality of life, both in terms of the fatigue, um, related to both drugs. But certainly there's a, uh, treatment burden with introducing upfront PARP inhibitor, the requirement for the transfusions. You're, you're essentially on an oral chemotherapy drug that requires a much more intensive version of monitoring than if somebody is on an ARPI alone. So you'd really like to know, is my patient in front of me going to live a better life by being on this drug compared to not being on this drug and giving it at progression. Um, which it's unclear how to identify who those patients are, um, especially given the potential for something catastrophic like AML, because in the, uh, ZZ first trial that was presented at the same time, 2 of 34 patients who are on talazopaib, uh, eventually developed AML with prolonged treatment. So, I think that it does give us pause around, um, You know, what the real risks of this are. So, I think in patients where, um, they have really aggressive kind of disease, they either, um, are not a candidate for a taxane, or they've had a taxane, and they're still not responding well. And you're very Worried that they're going to, um, progress in a way that's not easily salvaged, then this is something that we might consider upfront. But in patients with lower volume disease, with very low symptom burden of their cancer, I think, and where we think their overall survival might be somewhat prolonged, um, I think it does, um, have some pause that's associated with it. Um, as far as optimizing the patient experience for reduce, I, I don't know how many of us were actually using Q4 week denosumab. I think most of us were using Q12 weeks, so this really justifies, um, us doing that. It doesn't have any decrement in terms of outcomes, so that is great. I think Ericahog provided, um, great data around the, um, cognitive changes associated with these drugs, and Um, all of these assessments, uh, you know, as you go into the manuscript and see how the different assessments changed, um, over time with the two different drugs, gives a lot of perspective on, um, what to expect in terms of the patient experience. And, you know, just to talk about our dream briefly, it was a small study, but I think the, uh, Outcomes in terms of the number of patients who remained off treatment for more than 2 years after stopping was probably a bit more than what we would expect. And I think that it does give um opportunities for treatment breaks, especially in patients who had radiation to their metastatic sites of disease. Um, but I think that it's just a starting point to investigate intermittent strategies, um, moving forward. So, sorry I went long, but I just wanted to make sure that I Um, just, just, uh, kind of relevant aspects of all of these. Your, your ability to be comprehensive and nuanced is unparalleled. So I, I really appreciate your, your, your insights and, um, appreciate you and congratulations again on a dream. I think it's something that we're, you know, across the board, very, very proud of our, our enrollment in both a Dream, Erico and Proteus all done again, homegrown science here at Dana-Farber. Published July 1, 2026 Created by Related Presenters Michael Serzan, MD Medical Oncology View full profile Atish D. Choudhury, MD, PhD Medical Oncology View full profile
