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Neeraj Agarwal: So welcome to UroToday. We have Dr. Zeynep Ozay from Huntsman Cancer Institute, a postdoc fellow. And congratulations, Zeynep, for the ASCO Conquer Cancer Foundation Merit Award for the ASCO GU in 2025. So please tell me the title of your abstract. It was a pretty well-attended session yesterday.

A lot of the audience were curious about the effect of statins, which are such commonly used drugs, and how they are able to mitigate the cardiovascular toxicities associated with the androgen receptor pathway inhibitor, in this case, apalutamide. And you looked at two large phase III trials under the mentorship of Dr. Soum Roy and many others. So please tell us about your research. And what did you find?

Zeynep Irem Ozay: Yeah, thank you so much, Dr. Agarwal. It's an honor to be here and present our work today. And also, I feel so honored that we received the Conquer Cancer Merit Award for this work. And I truly appreciate this recognition from the institution.

So our work was on the association of statin use—we looked at the association of statin use and overall survival and cardiac adverse events in patients with advanced prostate cancer treated with apalutamide. And we did a pooled analysis of two phase III trials, as you mentioned, TITAN and SPARTAN.

Neeraj Agarwal: So patient-level data?

Zeynep Irem Ozay: Yes.

Neeraj Agarwal: You looked at, actually, patient-level data, not trial-level data, which is a major strength of any analysis.

Zeynep Irem Ozay: Yes.

Neeraj Agarwal: OK.

Zeynep Irem Ozay: Yes. So as our audience knows, statins are commonly used in clinical practice for cardiovascular disease prevention. And there are some studies that have shown that they could also have an impact on oncologic outcomes. But it's not fully understood or explored in prostate cancer. So here, we wanted to do a pooled analysis to see if there's an association between statin use and overall survival in patients with advanced prostate cancer receiving ADT alone or ADT plus apalutamide.

Neeraj Agarwal: So just to clarify for our viewers, these are large phase III trials. How many patients are we talking about?

Zeynep Irem Ozay: Yeah, so—

Neeraj Agarwal: Combining these two trials.

Zeynep Irem Ozay: Overall, we included 2,190 patients.

Neeraj Agarwal: So a very large number of patients. So you looked at 2,190 patients who were receiving either ADT alone or ADT plus apalutamide in metastatic hormone-sensitive prostate cancer or non-metastatic castration-resistant prostate cancer.

Zeynep Irem Ozay: Yes, TITAN was in patients with mHSPC, and SPARTAN was in patients with non-metastatic CRPC. And overall, among these more than 2,000 patients, 1,200 were receiving apalutamide. In our overall cohort, we saw that 700 patients were receiving statins. Among these, 484 were receiving apalutamide at the same time.

So we did this multivariable analysis to see if there's an association. And we adjusted our analysis for age, BMI, ECOG score, and cardiovascular diseases such as diabetes, dyslipidemia, and other vascular disorders. Also, we looked at patients' Gleason scores and tumor stage to ensure we had a comparable patient population for survival outcomes.

Then we categorized patients into two groups: statin-exposed and non-statin-exposed. Our results showed that patients who were receiving statins with apalutamide had better overall survival. However, patients receiving ADT with statins—ADT alone—did not have a statistically significant improvement in overall survival.

We also looked at cardiovascular adverse events in these patients. And we saw that statin exposure was associated with grade 3 or higher cardiovascular adverse events in both arms, which could be attributed to pre-existing cardiovascular conditions—more cardiovascular diseases these patients had. These patients were receiving statins because of these disorders.

But the interesting part of this study is that we saw a significant difference between patients who were receiving apalutamide compared to those receiving ADT alone. We think that patients receiving apalutamide have increased androgen suppression compared to those receiving ADT alone. And these patients receiving apalutamide are living longer.

So these patients are living longer, and they have more time to experience cardiovascular mortality during this time. When we give statins to these patients, they have more time to benefit from statins. And this helps reduce cardiovascular mortality in these patients.

Neeraj Agarwal: So very interesting data. So basically, for our audience, patients who had cardiovascular disease to begin with and were being treated with statins while on apalutamide benefited in terms of overall survival. And these data are pretty striking. And I think it tells us—please correct me if I'm wrong—that if somebody has cardiovascular disease and they are on ADT plus apalutamide in this context, it looks like they need to be on statins.

Zeynep Irem Ozay: Yes.

Neeraj Agarwal: OK. So what do you think are the implications of these findings? Because statins are already approved in the clinic. We don't need additional approval. We don't need prospective validation to get anything approved here. Statins are widely used medications. Apalutamide is an approved ARPI for patients with metastatic hormone-sensitive prostate cancer and also non-metastatic CRPC. So if they have cardiovascular disease, especially severe cardiovascular disease, it looks like they need to be on statins, doesn’t it?

Zeynep Irem Ozay: Yes, these data show that patients who are receiving statins at the same time as their ARPI treatment are getting more benefit in terms of overall survival. And this could inform clinical practice—especially for patients with cardiovascular diseases such as dyslipidemia, diabetes, or vascular disorders, they could gain more benefit with statin treatment alongside their ARPI treatment.

Neeraj Agarwal: What should I do as an oncologist? When I'm seeing these patients, I usually don’t prescribe statins. And also, there have been increasing concerns about cardiovascular morbidity and mortality in our patients with advanced prostate cancer who are on androgen-deprivation therapy with an ARPI as part of combination therapy regimens for years.

And I know there are many established investigators in the field of cardio-oncology who are closely looking into this area. As an oncologist, if I want to seek guidance—right now, we don’t have any tools to screen these patients in the clinic. What do you suggest I should do, or what should our viewers do, like me, like many of us in the field who are seeing these patients regularly?

When I’m taking the history and I’m seeing a lot of cardiovascular illnesses, doesn’t it make sense to send them to a cardiologist to have baseline screening for heart disease, such as an echocardiogram or EKG, and ensure they start statins if needed from the cardiology perspective?

Zeynep Irem Ozay: Yes, for sure, these patients should be screened before their treatments by a cardiologist. And we should know the baseline cardiovascular health of these patients before starting ARPIs. Because we know that for this patient population, the leading non-cancer-related mortality is cardiovascular disease. So it is just as important as their cancer treatment. We should ensure these patients undergo baseline screening and, if their cardiologist recommends, they should receive statins with their treatment.

Neeraj Agarwal: That’s great. And I know the American Heart Association has already put together a group of investigators who are looking at cardiac endpoints in oncology clinical trials. So I think we are already seeing increasing awareness of underlying cardiovascular disease, which may be a cause of mortality in our patients who are actually living much longer with their advanced prostate cancer on ADT plus apalutamide, and I would say, other ARPIs. So I think this is very meaningful research. And congratulations again on the Merit Award.

Zeynep Irem Ozay: Thank you so much.

Neeraj Agarwal: And I really hope to see these data published by you, Dr. Roy, and the team in a manuscript so we can share it with our colleagues.

Zeynep Irem Ozay: Yes, we are working on the manuscript currently. And I would like to express my gratitude to Dr. Roy. He is my mentor. We did this research with him, and I am so grateful for his guidance and support.

Neeraj Agarwal: Thank you very much for taking the time to join us today.

Zeynep Irem Ozay: Thank you for inviting me.

Neeraj Agarwal: Thank you.