Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

So I'm really excited to have er Doctor Lati joining us again uh to talk about advanced prostate cancer. And this time talking about evaluating emerging therapies in advanced prostate cancer. As you know, we like to frame our conversations around a patient so that we can take everything that we're saying back to the context of the clinic and more importantly the patient's life. So what we've got is a little fictional vignette that we've written and we hope to use that to, to frame our conversation in your mind about how this applies to patients. And the vignette is this mark, a 70 year old retired teacher was diagnosed with advanced prostate cancer. Initially, he responded well to standard treatments, but as cancer eventually progressed, necessitating consideration of new therapeutic options. Mark's case exemplifies the challenges and opportunities in staying current with evolving clinical trials, integrating emerging therapies and balancing cost with clinical benefit to provide, Mark with the best possible care. His medical team decided to navigate the complexities of new treatment protocols, assessing the risks and benefits of novel therapies like parp inhibitors and incorporating innovative remote monitoring and exercise interventions to enhance treatment outcomes and patient compliance. So as we explore Mark's journey, uh it's really important that we begin to think about uh the latest clinical data and that's what our conversation is gonna be about this evening. So, clinical trials are constantly evolving. Doctor from the latest clinical trial results in advanced prostate cancer. What are the key changes and updates in the evidence that colleagues need to be aware of in terms of changes in accepted clinical practice? Mhm So, um thank you so much. Um I am, you know, happy to speak on this topic and it's a very exciting one and this is a, a very uh unique time period in uh prostate cancer evolution. Um In that we have new treatment modalities emerging, what seems like yearly and new treatment strategies that are changing the standard of care, um you know, periodically uh and, and to a degree that the the standards are shifting um you know, very, very frequently and, and requiring us to uh maintain a very um firm understanding of, of the literature and that evolving data. So I'll start off um you know, taking a step back from Mark's circumstance. Uh you know, with him presenting as a um castration resistant prostate cancer through through which that has progressed on first line therapy. A lot of what is done in the castration resistance setting is contingent upon how we manage castration, sensitive prostate cancer, which you know, is, is defined essentially as treatment naive metastatic prostate cancer that which responds to some of our hormonally based therapies in the metastatic castration sensitive setting. There have been two landmark clinical trials published over the last 2 to 3 years, evaluating the value of triple therapy. So triple therapy, referring to a DT androgen deprivation therapy, in combination with um an oral novel hormonal therapy, specifically abiraterone or dalamide and and then in combination with DOCEtaxel chemotherapy. So these two clinical trials, one was called the A SN study. And the other one was called the P three trial. We randomizing patients to receive uh the three drug combination or a two drug combination, inclusive of of A DT with chemotherapy. The only difference between the two clinical trials was the oral hormonal therapy agent that was selective in P three, it was uh abiraterone and Ariens, it was dalamide. And essentially these two studies have um been reported in support that the use of a triple therapy strategy is superior to that of a double edge strategy including chemotherapy and injectable GNR agist antagonist, uh hormone therapy. The benefits have been demonstrated with respect to overall survival and progression free survival and um triple therapy has emerged as a new option for the management of metastatic castration, sensitive prostate cancer. Now, an important topic to um pay attention to is the fact that both of these studies were performed using chemotherapy and A DT as the comparator arm. No studies to date have demonstrated the superiority of a triple therapy regimen compared to an injectable hormonal therapy, GNRH agonist antagonist and one of the novel oral hormonal therapies. So we are left with somewhat of a dilemma understanding that triple therapy is not yet um the proven standard of care for all patients given this comparative um design. So, I it's a nuanced decision through which, you know, medical oncologist needs to navigate. Um the data currently supports the higher volume or higher risk prostate cancers. You know, particularly those involving visceral organ metastasis, probably benefit from the triple therapy strategy the most. But there still should be a, you know, significant number of patients that are receiving double it hormonal therapy, GNR H agonist with one of the horrible therapies. So it, it's a challenge that we are up against. But this late breaking um evidence does support triple therapy is a good option for many patients. Um So I'll pause here for a second to see if there's questions regarding this clinical trial. I guess what, what I'd love to um dive into Doctor Lti is the kind of identified uh risks and side effects, I guess with some of the more promising new therapy. So thinking about Parp inhibitors, for instance, um what can you can you maybe elaborate a little bit on that? Yeah, of course. And um you know, more broadly speaks to some of the newer agents that have been approved in castration, resistant prostate cancer. So, um you know, uh most patients having received hormonal therapy and now often chemotherapy in the castration sensitive setting. We are in dire need of newer and unique treatments for later line castration resistant prostate cancer. Um You know, as mentioned, parp inhibitors have emerged as a uh viable option for patients that have candidate genetic mutations. Uh in particular DNA damage repair mutations such as BRCA 12 and ATM. So Olaparib and um uh Luca and most recently, Tzar are parp inhibitors that have been approved in the castration resistant prostate cancer setting. Again, for patients with these candidate DNA damage repair mutations. This was based upon several clinical trials. Um And um even more recently, we are now given the option of combining parp inhibitors with novel hormonal therapies, specifically enzalutamide with Talib and um uh olaparib with abiraterone. The application of this combination strategy is again a little more tricky because the studies were done at inclusive only of patients that had never received an oral hormonal therapy. And as I mentioned, most patients are now currently receiving an oral hormonal therapy in the castration since you've said it. So it is a little bit of AAA data challenge for selection of the uh single uh single therapy option versus this double therapy option. Uh But we are gaining more insight day to day, which strategy makes sense, you know, to go back to the initial question and answer side effects are really a critical concern. Um As we talk about any new novel um uh treatment. Um in prostate cancer parp inhibitors have several AKI class side effects including tiredness. Uh In addition to uh low blood cell counts, we can also see issues with uh altered taste and diarrhea. Um anemia becomes a critical issue. Um Also un under the understanding that many patients with prostate cancer have preexisting anemia and looking at um you know, the registry trial for Talazoparib and Enzalutamide, in particular, many patients do require blood transfusions. So navigating these side effects requires, you know, close attention to detail, um frequent blood checks and touch points with patients to assess for symptoms. But in general, they're pretty manageable like the the the field of precision medicine is like rapidly advancing. And um I'd love to hear your thoughts on um how you envision the role of genetic and molecular profiling uh changing in in, in the guidance and selection of emerging therapies so that we can begin to increase the way in which we tailor our treatments for individual patients with advanced prostate cancer. Mhm. No, it's a really excellent question and that can you know, address it in, in several themes. So when one conventionally thinks of um uh personalized medicine in the in the cancer world, genetic testing is is front of mind. So we've already alluded to the fact that we have one genetically um guided medication option through parp inhibitors. Um There are others that are currently under development um one of which is uh immunotherapy. So, specifically keytruda pembrolizumab has been approved for essentially all solid tumors that demonstrate microsatellite instability, which is a, a feature that we will see on next generation sequencing. Uh Additionally, high tumor mutational burden on genetic testing can convey candidacy for pembrolizumab. Now, this is an important criteria. Understanding that immunotherapy for most men with, with advanced prostate cancer has not demonstrated benefit. But with these select mutations, we are finding candidates for the treatment to receive. Um uh you know, both palliative and um survival advantages. Um There are other mutations that are currently being considered. Uh There is a splice variant known as A R B7, which is appreciated to be uh one of the driver mutations for hormone therapy resistance clinical studies are underway to help guide both existing and novel hormonal therapies using a RV seven as a um AAA directy test um for the use or um uh omission of these treatments. We're also entering an era beyond genetic testing through which we're able to look for uh candidate proteins in the prostate cancer that allow for um your molecular targeting pluvicto or lutetium 177. PS MA has recently been approved for the the treatment of advanced prostate cancer. After patients receive chemotherapy and use of this drug is guided by a compendium pet scan. Diagnostic patients undergo PS MA pet scan which labels um prostate cancer for the candidate drug target prostate specific membrane antigen. And we're rationally selecting patients that have high expression of this target. Uh to receive the drug. We're poised to enter an era in which, you know, histologic and, and pet modalities are best selecting patients for various treatments. Um There are explanation uh ee you know, exploratory clinical trials, looking at antibody drug conjugates and novel radio ligans directed towards PSN A for patients that have neuroendocrine type prostate cancers, which is unfortunately a, an a not uncommon evolution of the cancer. Uh There is a tracer called DLL three for which um pet scans are, are under development and novel drugs including Bispecific antibodies and potentially radio likings. So, you know, as mentioned, personalized care of, of advanced prostate cancer patients are really um it, it is really developing well um and drawing everything back to, you know, the, you know, the initially um mentioning this patient um who is in dire need of newer treatments. II suspect that these tools um are on the horizon um to help benefit patients like him and others. I really love bringing you back to that, that patient, right? And uh and as you said, it, it's quite a promising time for er for patients with advanced prostate cancer like Mark and, and that's what this is all about. So, uh we're really grateful um Doctor Li for, for your time today and uh thanks for giving us such a comprehensive um update on some of the latest evidence and accepted practice. Thank you. My pleasure. Thank you very much.