Dr. Anari presents updates on Metastatic Prostate Cancer
So we're going to go over some updates on trials and some new trials and some new approvals and time permitting some future directions. So the first item on the list is the long term results that represented for uh stampede. Um As you know, it's a randomized multi are multistage trial. Uh This update was on arm G. Which I'm sorry auntie, which is a. D. T. Standard of care plus abiraterone. The analysis included 1000 patients with Metastatic disease at Baseline. There is a median follow up of 6.1 years and the primary endpoint is overall survival. So here you can see that the patient characteristics were pretty balanced in both groups, median age was 67. Uh majority of the patients had newly diagnosed disease and they included both low risk and high risk for latitude criteria. And as we would expect, phone and distant lymph nodes were the most common sites of metastases. And here we will go over the key outcomes of this trial. So as you can see here, the five year median overall survival with 60 60% among those in the abiraterone group compared to 41% and those who received a. D. T. Alone. Um And this corresponded to a 40% relative improvement in overall survival. Um And then in terms of absolute benefit Um there was 2.8 year overall survival benefit. Those who received abiraterone at a 6.6 year median overall survival compared to 3.8 years and 80 T alone. And this benefit, these next few slides will show extended across low risk and high risk disease per latitude as well as low volume and high volume disease per charted. And then here you also see the benefit is over uh seen in failure free survival and progression free survival. Um Also the benefits seen here is on the order of years as well. Mhm. And then lastly, I want to highlight that in those receiving abiraterone. There was a decreased risk of a skeletal related event that could be bumping requiring radiation or surgery. It could be metastatic disease causing cord compression or pathologic fracture. Um So that was all decreased in the abiraterone arm. And then for all A. S. Uh there were no new Um adverse events signals seen on this updated analysis. And as you can see, there was 16% grade three and above events in both groups. So here, you know, the conclusions in my mind, there are significant benefits on the order of years. Um And there's no new toxicities and there's a decreased risk of skeletal related events. Um So in my mind that is really just consolidates our current use of abiraterone and predniSONE in the metastatic hormone sensitive space. Next we'll talk about the hero trial that was presented at Asco 2020 this year. So here's the scheme. This included men with advanced prostate cancer. There they were randomized 2 to 1 to reload Alex, which is a g G N R H antagonistic or versus lou Barletta GN Rh agonist, which we commonly used with a primary endpoint of assisting castration through 48 weeks. Here, you'll see that about 22% of men have newly diagnosed hormone sensitive metastatic cancer. And then if you look on the bottom, over 90% of men had cardiovascular risk factors and about 13-15% of men had a history of a major cardiac event. And here you'll see that removal is performed really well achieved. Its primary endpoint of sustained castration through 48 weeks. Um, in 96.7% of men and the rolex arm versus 88.8% in the loop relied arm. Yeah. And then here you'll see some other key secondary endpoints, 80% of men in the oral A. D. T. Arm had A P. S. A. Response by day 15 as opposed to 20% the Lupron right arm. And then men, uh there was the probability of castrate castration at day 15 was almost 99% in the oral A. D. T. Arm versus 12% in the loop relied arm. This, I think is probably one of the most interesting um points that was made. So the time course of testosterone suppression. So if you see all the way on the left with just as you would expect with a january antagonist, the Rolex really dropped that testosterone really quickly as opposed to with Loop relied, you know, you get that initial spike and testosterone. And then in this subset here, 184 men, it shows in men who had one year of therapy after they discontinued it, there was a pretty rapid recovery of testosterone in The, in the men who were on the Beluga licks Arm vs liberalized at 90 days. Many of them still had castrate levels of testosterone. And then also interestingly, you know, the risk of major adverse cardiovascular event was 2.9% in the Rolex arm versus 6.2% in the Lupron light arm. But if you look at men who had a history of a major cardiovascular event, which are very many of our patients that walk into the office, um, there was a sixfold decrease in chance of having another major adverse cardiovascular event in the Rolex arm. So that part was really impressive to me and could be a potential way to dictate who might get these treatments in the future. So, again, this study met all of its primary and secondary endpoints. The testosterone recovery was really impressive in the Rolex arm as well as the potential cardiovascular benefits. So this has potential to be practiced changing. It's not approved yet. So we talked a little bit about the pros in my mind. The potential cons are tied in with one of the pros and that its oral therapy so that leads to potential compliance issues. Um Testosterone monitoring will need to be much more frequent to ensure that patients are taking their medication. Um and the cost of oral therapy and access to oral therapy has potential to be an issue as well. Next, we'll talk about park inhibitors in metastatic castrate resistant prostate cancer. We have two new approvals that will talk about. Um but the reason why this is so exciting is in 2016, the Pritchard at all group had 692 men with metastatic prostate cancer. And they sequenced 20 DNA repair genes and found that UN selected for family history. About 12% of them had a mutation in a DNA repair genes. BRCA two was the most common. So in May of 2019 we had two approvals, one for root cooperative and another for a lap a rib. So we'll go into the trials and why those got approved. So in Ruka prib triton to um is a Phase two trial that evaluated rockhopper of in patients with metastatic castrate resistant prostate cancer who had a deleterious baraka mutation. Um And this was this trial included men who had already received androgen receptor targeted therapy as well as a taxing chemotherapy. Um So that's important to note that they had to have had both oral and chemotherapy and the primary endpoint here is objective response rate. So what you'll see here highlighted is the conf firmed objective response rate by independent radiology review was 43.5%. Um And that included complete and partial responses. But you'll see here that 89% of men had stable disease or better. Um And the confirmed P. S. A. Response rate was around 55%. And in terms of safety um The biggest signal that we saw was uh in anemia in terms of the grade three and higher events followed by thrombosis to pina and fatigue here. This is approved and indicated in patients with a B. R. C. A one and two mutation in the castrate resistant space after both are targeted therapy and taxing based chemotherapy. And it's really an important reminder to get Semitic and germline testing in patients with advanced prostate cancer. Um And there's a Phase three trial and three study that's ongoing that we won't go into the details tonight. Um Next is the phase three profound trial. That is a study that was the updated overall survival of cohort A, which included B. R. C. A. 12 mutations and A. T. M mutations. The overall survival was um Given an Asthma 2020 this year. So the primary endpoint which was met and uh presented previously was Radiographic PFS. And then the secondary endpoint that was presented as the overall survival in cohort A. And these patients were castrated, had castrate resistant disease. They were randomized to elaborate or physician's choice, which was either abiraterone with predniSONE or and solidified. And notably this study did allow for crossover. So here this is just a brief slide on the radiographic progression free survival benefit seen with Ola prib 7.4 months versus 3.6 months in the Enzo or Abby arm. And then this is the updated analysis. And you can see here that in uh cohort A again that's B. R. C. A. One and two or 80 M mutations. The elaborate arm had a median overall survival of 19.1 months versus 14.7 months with a hazard ratio of 0.69 meaning that the risk of death was 31% lower with the elaborate group compared to the control group. Um And then because crossover was allowed, there was an adjusted analysis of overall survival which showed a hazard ratio 0.42 So this analysis really showed an even larger benefit to the use of L. A. Probe in cohort a a little bit on safety. Again, the most notable grade three or higher toxicity was also anemia. Similarly to Rock Opera. So here we did see improved overall survival and men with castrate resistant disease and a mutation and B. R. C. A. 12 or a. T. M. After Abby or Enza. Um It's currently the approval right now for the FDA is actually in all homologous recombination repair mutations, both somatic and germline after a are targeted therapy has a broader label than recap a rib and no prior chemotherapy is necessary. So I just want to spend a quick minute talking about the therapy trial. So this is something that was presented at 2020 AsCO again and this was to determine the activity and safety of Leticia PSM A. When compared with Capozzi Taxol, this study included men who were already been treated with those attacks. All had progressive disease. Um And you know this study they did have to have um no F. D. G. Avid uh sites of disease that were PSM a negative as well. So there was a very highly selected group that was able to enroll. Um And a little bit on Leticia mps. Emma. It's a radio labelled small molecule. It binds with high affinity to PSM. Which is highly expressed in metastatic prostate cancer. So it enables the beta radiation to go to the sites of disease with minimal damage to surrounding tissues. Um And their primary endpoint here was a P. S. A. Response. And you know they met their their end point again. This is an early trial. There's more trials coming out but I just thought it was interesting that there was a 29% absolute greater P. S. A. Response. So my take on points here are I think it's very interesting. We didn't go into all of the great 34 A. S. But it was actually looted mps and they had less than capacity Taxol. Um I wouldn't say this is practice changing just yet. Um There's a vision trial coming out which compares standard of care plus Leticia psm versus standard of care. A. P. S. A response of 50% or more is not necessarily a surrogate for overall response. So just something to keep an eye out on. So you know my conclusions. I think the stampede trial supports supports our current practice of using abby pet and abby pratt in the metastatic castrate sensitive space in both high risk and low risk disease. Um The hero trial oral A. D. T. Has not yet approved. But I think it's a very interesting option especially for men with um cardiovascular disease. The tried and true and profound trials really emphasized the importance of getting both germline and somatic testing if possible on our patients. And again the therapy trial. It's not practice changing but has potential to be an effective treatment and are heavily pre treated money with metastatic prostate cancer. So thank you very much. And I hope you enjoy the rest of the evening.