Comorbidities, Adherence and Dose Alterations in nmCRPC


A prostate cancer expert discusses comorbidities and dose alterations with next-generation androgen receptor inhibitors in nmCRPC.

Audrey Sternberg: Switching gears here, what comorbidities do you most commonly see in patients with nonmetastatic castration-resistant prostate cancer? What comorbidities are most likely to impact your treatment selection?

Aaron Berger, MD: Being here in the Midwest, we have a fair number of patients who have some obesity issues. That’s probably true everywhere. Does that really affect what treatment we’re going to give them from a prostate cancer perspective? If they don’t have significant cardiovascular issues and haven’t had a heart attack, strokes, or CHF [congestive heart failure] issues, I’m not going to withhold a second-generation antigen inhibitor just because they’re a little overweight. But we certainly see a lot of that. We see a lot of diabetes and heart disease. Those are the most common things we see. We see some patients with renal insufficiency. The nice thing with all these medications is that they’re safe for the most part—at least as far as the studies go—to use in patients with renal insufficiency. You don’t need to do any dose adjustments if they have some renal insufficiency. But obesity, cardiovascular disease, and diabetes are probably very common everywhere in the United States. Certainly, they are in my area.

As far as directing therapy, I don’t think there are great data to say, “If this person has diabetes or high blood pressure, we should use one medication vs the other.” It’s a matter of educating the patients about all of the potential adverse effects and then making a decision, with the caveat that if patients have some neurologic issue, like unsteadiness, dizziness, or history of falls, then the data would indicate that darolutamide [Nubeqa] may be a better option, as there wasn’t any increased risk in falls and fractures in the ARAMIS trial. That may be 1 comorbidity that we’d help direct treatment. But otherwise, there isn’t a huge difference for common comorbidities—diabetes, hypertension, and obesity—in one vs the other.

Audrey Sternberg: How often do quality-of-life issues lead to dose reductions, interruptions, or nonadherence to treatment?

Aaron Berger, MD: As far as nonadherence, some patients just aren’t compliant. Even if they’re not having an adverse event, they just forget. They may be busy or have other issues. That’s happened where we have patients come in and they’ve been doing well, but their numbers suddenly start going up, and they say, “I haven’t been taking my pills for the last 2 months.” That can happen regardless of adverse events depending on the patient.

As far as frequency of dose reductions, as I mentioned earlier, it’s not real common. Occasionally with enzalutamide [Xtandi], we’ll decrease the dose if there’s some significant fatigue. I’ve done dose reductions with all 3 of these medications for various issues, whether it’s fatigue, some GI [gastrointestinal] upset, or muscle issues that are very nonspecific. But we try to see if it’s caused by the medication before we switch over, because in general, these medications all work very well. If we’re going to stop it, interrupt the dosing, or move on to something else, we want to make sure that the adverse event is really from this new medication and isn’t from something else that their primary doctor gave them for their diabetes, hypertension, or something else. Because oftentimes, we’ll reduce the dose or stop it altogether for a couple of weeks and the symptoms they were complaining about are still there. Clearly, it wasn’t from the medication.

None of these medications have an extremely long half-life. If you give it a week or 2 break and their adverse event is still there, it’s not from the apalutamide [Erleada], enzalutamide, or darolutamide. It’s from something else. But it’s not real common. Since the apalutamide approval, I’ve stopped it on 2 patients who had significant rash. With enzalutamide, I don’t know an exact percentage, but we have some patients who have done a dose reduction but do fine. And with darolutamide, that one hasn’t been out quite as long, so I don’t have quite a length of experience with that, but we’ve done a bit of a dose reduction on that for some patients for fatigue or things of that nature. But again, is that related? Is it just because they’re tired because they have cancer and are on androgen deprivation therapy? It’s hard to say. But whether it’s placebo effect or an effect of the medications, they often do feel better. But a slight dose reduction, at least in my experience, hasn’t led to a significant decrease in the efficacy of the medications.

This transcript has been edited for clarity.

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