The Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute presents a succinct summary of all the prostate cancer clinical updates you need to know from ASCO 2024.
Thank you all for joining this evening for our as o annual meetings, uh highlights of 2024 prostate cancer. Um I think we learned a lot about radio and therapies. We've learned there was actually a phase three trial that um that I was unaware was open um which was reported, which was very exciting to see. And then um some uh an abstract actually on uh on quality of life and, and hot flash management, which is certainly something we see in the clinic almost on a daily basis. So the first two abstracts that we talk about our health related quality of life from the PS A four study, this was presented by Dr Karim Beati. Um For those who may not be aware of PS MA four was a randomized phase three clinical trial for patients um who are attacking naive in the CR PC setting. Um and randomized patients to mutation, PS MA once every six weeks or six cycles. Um Well, uh compared to A RP I change. So Abby or Enza importantly, the crossover was allowed on this study. So patients were allowed to cross over if they had a disease progression by the IC R. So we know that um this was data presented back in the fall that radiographic progression free survival was improved on nutrition relative to A RP I change with a hazard ratio of 0.343. Um We also saw some updated data here that overall survival was zero point was um similar between treatment groups with the hazard ratio of 0.98. Again, with the caveat being that there was a high rate of crossover for patients who were treated on A RP I change. About 60% of patients eventually got Mutis um after progression on their A RP I change. And so what this analysis was looking at was health related quality of life in a couple of different domains. So first in prostate cancer specific on the PFP measure and a generic measure called EQ five D five L um or on chronic pain and several different measures. And so what um these analyses showed was that um health related quality of life um was improved uh on, on nutrition relative to A RP I change. And we saw um in the fact P score, the hazard ratio is 0.59 in the generic EQ five D five L utility score, that ratio was 0.61. Um We also saw that time to worsening pain intensity was um better on POTI compared to A RP I change. Um and really across all pain domains. With hazard ratio is well below one co from central intervals, also below. Um we also know that nutrition um did have higher rates of uh dry mouth asia um some cytopenias relative to a ARP I change. Um But again that um Texas city data was not new here. So um what this analysis showed was again, we know the um clinical efficacy of nut in the pre taxing CR PC space and that um the health related quality of life and pain measures really, I think added an, an additional piece to the puzzle that we know nut is a well tolerated therapy and um a a and one that um we hope will be available to our patients um prior to receiving tax in based chemotherapy. Whereas now it's only available for patients who have received um tax I based chemotherapy in the CR PC setting. Um The next really important analysis was also done on the PS MA four study, but it was looking at a baseline CT DNA analysis and um on the PS MA four study, this was presented by Johan De Bono. And what they looked at was um several different treatment times and they looked at baseline levels of CT DNA um at cycle one, cycle two. And what they did was look at a customized 85 GCT DNA panel and estimated CT DNA fraction. And then associated that with several outcomes including radiographic progression free survival. PS A 50 as well as resist response, we see at baseline, that median CT DNA fraction was balanced between treatment arms and so AC T DNA fraction, um, greater than zero point point 5% was in, um, was seen in about 65% or two thirds of patients at baseline on either treatment arm. And then you see, um, on the nutrition arm, that CT DNA fraction decrease, uh to 38% at, um, icy two day one point relative to 40 47% on the A RP I change. Um, we saw that higher levels of baseline CT DNA fraction was associated with a shorter rate progression free survival regardless of treatment received. And I think intuitively that makes sense to us if there's a, a higher burden of tumor, if there's a higher CTD fraction of baseline, whether you got nutrition or A RP I change. Um, your, um, you, you, um, your outcome was associated with a shorter rpfs. And then when we look at, um, at the CT DNA fraction, um between two arms, um, we see that um RPFS was improved on the nutrition arm relative to a ARP I change regardless of what your CT DNA fraction was at baseline. And that's perhaps not surprising to us. We know that A RP I change probably is not a great um, a comparator arm in this trial. And, but it is encouraging to see that uh wer did, um fare better. Really importantly, we look at the dynamics of CT DNA clearance. And so on the left hand side, I want to highlight that patients who were um detectable at baseline and then as they were treated with NR PS MA became non deet, so that small subgroup of patients in purple, we see that they had were associated with a prolongation of radiographic progression free survival. Um But then we look at some of the other subgroups and obviously patients who were nondetectable and stayed non detectable, they had the best rpfs and then patients who were detectable, um uh were not detectable and converted to detectable. Those patients had had poor outcomes and those are all kind of clustered in the, the lower left part of the graph there. Um When we look at specific subsets of um of mutations analyzed. So again, this was a 585 gene panel, but then they selected focused in on 18 genomic features that were pre pre prevalent in greater than 10% of patients. And these are some of our known prognostic biomarkers. So A R amplifications uh chromosome A Q or myth amplifications, tp 53 deletions P I three kinase. Um And it really asks the question, does the presence of these mutations correlate with outcomes on nutrition therapy? Um And unfortunately, it looks like they do. Um And so the presence of any of these um mutations, uh A Q amplification A R amplification or TP 53 they were associated with a lack of response to uh mutation PS MA therapy, which is um you know, really, I think an unfortunate finding but really an intriguing biologic question to be asked and to kind of be explored further. So again, conclusions from this abstract was um higher baseline CT DNA fraction was associated with a shorter RPFS. And that some of those early CT DNA fraction changes, namely going from detectable to undetectable was associated with an improvement in RPFS. Whereas going from undetectable to detectable was associated with a worse radiographic progression for survive. Um I will highlight just at one of our ongoing studies of the PS MP S MA here at a harbor. This is the lo cargo study being led by Doctor Prole Ravi and Doctor Heather Gin. Um This is for patients with MC RT C who have received prior tax in this chemotherapy. And um it's a phase one study. So, really exploring what is the recommended phase two dose of nutrition plus several different doses of carboplatin. And again, this is actively enrolling in something we're looking forward to um to advancing here at Dana Harbor.
