Patients with mCSPC achieve a deep PSA response faster with apalutamide than enzalutamide, study shows

At the 2022 ASCO Genitourinary Cancers Symposium, investigators reported that patients with metastatic castration sensitive prostate cancer (mCSPC) experienced a deep prostate-specific antigen (PSA) response, or PSA90, faster when receiving apalutamide (Erleada) than enzalutamide (Xtandi).1

In this interview, lead author Benjamin Lowentritt, MD, FACS, discusses why the findings of this study are so important in future counseling for mCSPC. In particular, he mentions that the difference in PSA90 response to these 2 drugs should lead to further research of this population in the community urology setting. Lowentritt is the director of minimally invasive surgery and robotics and the director of the Prostate Cancer Care Program at Chesapeake Urology in Baltimore, Maryland.

Please discuss the background for this study.

This [study] is great because we were able to use real-world evidence from a number of larger urology groups and understand data directly out of their [electronic medical record (EMR)] using a third-party software. So, it allows us to get deeper into questions that otherwise are a little bit harder to really understand after an approval. This was a really interesting opportunity. It came out of some work that we had done before looking at adherence and use of different medications in different disease states for advanced prostate cancer. From that, we developed some other ideas, and this was the first one that we've come up with, seeing if there's a comparison between different medicines used for the same indication. Although we can't do that easily when we're looking at 2 different trials, when we're looking at the same population, it's a little bit easier to see if there's some trends there that might be of interest.

What were the notable findings of this study? Were any of them surprising to you or your co-authors?

There was a surprise because I think the gut feeling that a lot of people have, especially with some of the novel hormonal treatments that are testosterone receptor blockers or androgen receptor blockers, [is] that they're all the same. At least the suggestion from this study, which looked at the depth and sustainability of a PSA drop in patients that are starting either apalutamide or enzalutamide for metastatic castration-sensitive prostate cancer, or mCSPC, was able to show a difference between those 2 drugs. [This was] a pretty significant difference, too, of how many patients achieved a PSA90, how quickly it happened, and how it was sustained. So, I think the message was a little bit of a surprise, because I think we all started from the hypothesis that there wouldn't be much of a difference.

How will these findings impact the way that you treat mCSPC in the future?

I think there's always a word of caution in data like this. This wasn't a prospective, randomized trial, and it does involve abstracting data out of an electronic medical record, which can be difficult to make too broad of a statement based on. But I do think that it makes me really want to evaluate whether I'm choosing the right medicine for the right patient every time. I think we always did that before, but like I said, there was always this sense of equivalence. Maybe there are some opportunities to say, "Okay, these patients may do better on one medicine or another." I think, certainly, there are other factors that go into these choices, from side effects to particular patient characteristics and comorbidities, but I do think that this helps inform how to choose an agent for this specific stage of the disease.

Is there further research on this topic planned? If so, what will its focus be?

From this dataset, certainly, we're still working on some other projects, both looking at other agents that were used in considering same kinds of comparisons with other agents. I also hope that this would lead to other either institution-initiated or individually initiated trials by investigators to look at this question on a prospective basis, specifically looking between apalutamide and enzalutamide. I don't know that we're going to be doing this specifically, but I think that is an opportunity that this would be helpful, just to see if that's something that bears out prospectively.

What is the take-home message for the practicing urologist?

I do think that we need to consider each of these drugs on their own. I think experience dictates a lot and we've all had a lot of success, hopefully with multiple of these agents. But if you haven't tried one medicine before, you might want to give it a shot and understand that they truly are different, and we might see different responses in different patients. I think we're at a point where we have this luxury of many options, which is great, but we still need to continue to be really thoughtful in how we choose those options.

Is there anything else you feel our audience should know on this specific topic?

I really was happy that this approach was taken and involved community urology. I think that the academic centers do a wonderful job in taking care of patients and also the studies that involve some community sites are always very helpful. But this kind of work [gives] a much broader look at what happens outside of highly controlled and highly selected patient groups that are in clinical trials. This real-world evidence approach is growing as an important way to use all of the data that's in our electronic medical records to answer some of the questions that we really need answered [in the future].

Reference

1. Lowentritt B, Pilon D, Khilfeh I, et al. Attainment of early, deep prostate-specific antigen response in metastatic castration-sensitive prostate cancer: A comparison of patients initiated on apalutamide or enzalutamide. Paper presented at: 2022 ASCO Genitourinary Cancers Symposium; February 17-19, 2022; San Francisco, California. Abstract 43