Rashid Sayyid: Hello everyone and thank you for joining us today in this UroToday Journal Club recording. I'm Rashid Sayyid, an assistant professor Urologic Oncologist at the Department of Urology at the University of Arizona, and I'm joined today as always by Zach Klaassen, associate professor and program director at Wellstar MCG Health in Augusta, Georgia. And today we're going to touch upon a very important publication in the literature that really is key to elevating the prostate cancer patient's voice, and allows us to better understand their treatment preferences to allow us to better design studies in the future and also provide care, which is more in line with the patient's goals and preferences. This important publication was recently published in the Advanced Therapeutics with Dr. Elizabeth Kessler as the first author. So when we take a step back and look at all the agents that are approved currently by the FDA in the advanced prostate cancer space, we see that we have nearly 20 agents that are approved and across various different subgroups, ADTs, ARPIs, chemotherapy, you have the immunotherapy, radiopharmaceuticals with radium-223 and lutetium-177, as well as PARP inhibitors and some combinations of these drugs.

And even within the same umbrella or class of drugs, we see different agents that act differently in terms of how often they're dosed, whether they're taken orally, SubQ, IM. So really when we consider that we have these additional approvals and all these options, it's great for our patients, but also there's really some key downstream effects that we need to consider when thinking about one agent versus the other and what works better for our patients, both from an efficacy standpoint as well as a patient preference standpoint. And one of the key things we need to highlight is the issue of polypharmacy and treatment non-adherence that comes with that. And polypharmacy is defined as taking five or more medications, and it's really quite ubiquitous in the older cohort of patients where it affects almost half of men who are 65 years of age or older. Why is this important relevant in this patient population?

We know that polypharmacy is associated with treatment non-adherence, which obviously can lead to negative outcomes in prostate cancer care. In addition to polypharmacy in and of itself, we really need to consider other things that can further exacerbate treatment non-adherence. First thing is the route of administration, whether it's oral, IM, SubQ, IV, that's really important for patients. How often do they have to take the pills? Is it daily, two to three, four times a day? How many pills are involved at a time? Do they have to take it with or without meals? All of these are important things. Patients are not always educated as we would hope or expect, and really that has an influence on non-adherence. Sometimes something as simple as having a hard time swallowing the medication can have a really profound effect, and impaired cognitive function, which we know is increased with these ADT agents.

It really is something that we need to consider in this setting. So what do we already know about polypharmacy in the prostate cancer literature? First, we know that adherence to oral therapies is low, and it's even worse in patients who have a symptomatic disease burden. And adherence can be improved when treatment is more effective and improves pain burden, which makes sense. Patients are more motivated to take their medication. And when we query patients in the past and we ask them about their treatment priorities, the most important thing for them as we would expect is treatment effectiveness. The treatment has to actually work. Second, it needs to be accessible. Third, it needs to have a positive or net neutral effect on the quality of life. And really the side effect profile should be favorable. So things that are, we can think about, but we don't always do a great job of verbalizing and taking into a priority.

And so the study objective was to address what remaining gaps are in the literature by better understanding our patient's preferences around therapies for prostate cancer and focusing specifically on three different topics. First of all, the type of treatment, be it IV, chemotherapy or oral meds, which becomes especially relevant in the advanced prostate cancer setting. We need to better understand pill burden as well as treatment frequency in this space. To accomplish this, the study investigators conducted a cross-sectional online survey of metastatic prostate cancer patients residing in the USA in January of 2024. These patients were invited to participate via an email, take the survey, and they provided online consent. They were administered 15-minute surveys with 27 close ended questions under the following three umbrellas. So first demographics to better understand who are these patients that are being queried better understand disease area specific questions. And what do I mean by that?

Different questions pertaining to treatment, adherence, pill burden, and then exploratory questions about the routes of administration, be it IV, chemo versus oral treatments. And the data in this study were analyzed using the online survey platform tool, the Alchemer and Microsoft Excel, and these were descriptive in nature given the obviously nature of this study. And at this point, I'll turn it over to Zach. We'll go over the demographics of results in this study, better understand the patient preferences, and then he'll do a great job as always contextualizing these results within the context of patient care in this setting.

Zachary Klaassen: Thanks so much Rashid. Always a great introduction and to level set for the results of these kind of studies. And so when we look at this particular survey, this was distributed to 200 men, 103 men participated, and in terms of complete survey responses, a hundred men completed these in full. So this is with the breakdown of the demographics for all these a hundred men. We see that median age was 65, roughly, not surprisingly, 74% of men were 60 to 79 years of age. When we look at race, I think what's important here, and I've added an asterisk, is that 31% were black or African-American. We know that these men are typically willfully under recruited to phase two and three clinical trials. And so a real world representation of who we really treat in our clinical practices. In terms of highest level of education, we see a smattering across all levels of education.
4% post-graduate, 27% bachelor's degree, 19% associate degree, 17% trade school, 10% said some college and 19% said high school education.

Some additional results that I think are worth pointing out. So when we look at additional demographics, we see that 86% of men receive care from an oncologist, 13% from a urologist, and one of these patients did receive care from their general practitioner. When we look at pill burden, this was a highly treated patient population. So taking oral treatment for prostate cancer, 80% of patients. As Rashid laid out, more than five pills per day, 48%, more than three medications per day, 50%, and patients that were taking medications greater than one time per day. So maybe in the morning or in the evening, 64% of patients, roughly two-thirds of patients. I think this is an important point. So when we look at important features when starting a prostate cancer treatment, the most important feature when starting new treatment for patients, 67% said where they need treatment.

So whether this was home versus infusion center, this really matters to patients of where they actually have to receive their treatment. So the next several slides, we'll look at some of these important questions that were asked in the survey. The first one looks at agreement regarding pill burden and impact. You can see down here for all of these figures, the schema is agree, dark blue, neither agree or disagree, blue. And then light blue is disagree. And so 91% of patients agreed that they prefer one pill once a day treatment. 59% said they do not prefer regimens that require multiple pills per day. 53% said they're concerned about accidentally forgetting pills or taking the wrong dose or tablet. 51% said the more pills they take, the sicker they feel. And it was relatively balanced with regards to the question of the more pills I take, the more likely I am to need help.

This figure looks at the barriers to take oral cancer therapy multiple times each day. The most important barrier to taking oral cancer therapies was remembering to take the pill multiple times per day. 63%. 52% said a barrier was carrying multiple pills when leaving home. 43% said having to eat food multiple times each day was a barrier. 32% said having to fast for two or more hours before taking the pill. And 18% of patients said they had the difficulty swallowing pills. So this really highlights the importance of all of these issues with taking pills and some of the barriers expressed by the patients.

This figure looks at challenges related to taking oral treatment for prostate cancer multiple times per day. 74% said they may need to take the pills with them when they leave home and they prefer not to take multiple pills with them on the road. 68% said they may forget to take multiple pills at different times of the day. 61% said they may feel nauseous after taking the pill and prefer not to feel nauseous multiple times during the day. 50% said I prefer to eat food when I take my pill and may not have food available or may not want to eat several times per day, and 47% said they may need to wake up from a nap or from a deep sleep to take the pill. So these are some challenges expressed by the patients with regards to oral treatment for prostate cancer.

No surprise here. When we look at preferences for oral treatment versus intravenous chemotherapy, 89% of patients prefer oral treatment. Only 1% of patients prefer intravenous chemotherapy over oral treatment. So by way of discussion, this survey of patients with advanced prostate cancer showed that almost all patients choose a one-pill once-a-day regimen over a multi-pill regimen, and they also would rather choose an oral treatment option versus IV, chemotherapy. Secondly, one in five patients report a difficulty swallowing medications whole and most saw value in medications that can be dispersed in liquid or an applesauce, particularly for those that have swallowing issues. What's important for clinicians is that many patients may not readily mention these swallowing difficulties. So the burden is on us to proactively discuss potential administration challenges with our patients when we're deciding treatment options. Several important strengths of this study. This was a diverse population. As we mentioned, this said 31% black or African-American patients and various levels of education level, and all patients surveyed were actively receiving treatment for advanced prostate cancer.

Of course, with any study it's important to mention limitations For this study, there was relatively small sample size. There may be potential for selection bias, for example, there were no questions related to radioligand therapy. We know this is moving further up in the prostate cancer disease space, this was limited to IV chemotherapy versus prostate cancer, oral medications. And finally, the study was solely conducted in the United States, so perhaps may or may not be generalizable to other parts of the world. So important take-home and concluding messages. This survey is one of the first to understand patient's preference regarding oral treatment for advanced prostate cancer. Secondly, the results underscore the importance of shared decision-making and consideration of a patient's preference when prescribing a prostate cancer treatment that will ensure the best opportunity for adherence. And finally, these factors can impact both long-term outcomes and a patient's quality of life. We thank you very much for your attention to this journal club discussion for UroToday. We hope you enjoyed it. Thanks so much for your attention.