Updated Safety Data and Treatment Selection in nmCRPC


Dr Aaron Berger shares updated safety data on next-generation androgen receptor inhibitors and impact of safety profile on treatment selection in nmCRPC.

Audrey Sternberg: Can you discuss the updated safety data for darolutamide and apalutamide that were presented earlier this year at ASCO [2021 American Society of Clinical Oncology annual meeting] and ESMO [European Society for Medical Oncology Congress 2021]?

Aaron Berger, MD: Yes. It was a longer-term evaluation of the adverse effect profile of these drugs that was presented earlier this year. It basically reinforced that the adverse effect profiles are very similar, even with longer duration therapy. As I mentioned earlier, darolutamide didn’t have a significant increase in any of the common adverse effects over placebo. And with apalutamide, they did quality-of-life surveys along with the adverse event surveys. The quality of life wasn’t significantly impaired vs placebo for the patients who were in the apalutamide arm. The updated data reinforce that these are very safe, effective, and have a very low incidence of significant adverse events for all of them.

Audrey Sternberg: Can you discuss data about the timing of adverse events with these agents, specifically as it applies to the ARAMIS trial?

Aaron Berger, MD: As far as the timing goes, in my experience, most of the fatigue or any other significant issues with darolutamide are typically happening relatively early. That’s true with all of them as far as adverse events such as fatigue and dizziness. But with the prolonged exposure to these medications in the follow-up data analysis, there weren’t any significant adverse events that suddenly started happening with longer-term follow-up. It was pretty consistent with the early data.

Audrey Sternberg: You touched on this earlier, but is there anything else you’d like to mention about the treatment of adverse events when your patients manifest these during treatment?

Aaron Berger, MD: With any new medication, you want to make sure patients understand. We try hard to get patient education materials for all 3 medications. The companies behind them provide very nice patient information handouts to go over proper dosing and potential adverse effects. And then it’s incumbent upon us as the prescribing physicians to understand their other medical issues, the other medications they’re on, and to work with our pharmacy staff or the pharmacist who’s dispensing the medication to make sure there are no significant interactions. Those things get very complicated with all the drug-drug interactions. There are so many new drugs coming out for all sorts of other disease states, whether it’s high blood pressure, diabetes, or other cardiovascular issues, that it’s very hard to keep track of all the drug-drug interactions. We rely on our pharmacy software as well as the pharmacist to help us with that. That’s really important to make them aware of.

As far as overall management, certainly give them expectations of what may potentially happen. I don’t think we want to try to hide potential adverse effects. We want to be up front with patients on what may potentially happen. But the overall message is the incidence of significant high-grade adverse events with any of these medications is fairly low compared with placebo in all the trials, and they’re very effective. It improves their overall survival and metastasis-free survival. And for these patients who have progressive cancer, that’s No. 1 at the top of their mind. They’re not necessarily worried up front, “Am I going to get a little tired? Might I get a rash in 3 months?” That’s not their main focus. Their focus is to get their cancer under better control and to get their PSA [prostate-specific antigen] down. These patients get very focused on that number, as we do as well. We want to try to get the numbers down for them, which certainly gives them good reinforcement.

But if they have any significant new symptoms, no matter what they are, they’re encouraged to call us—myself, my nurse navigator, the pharmacy—and then ask, “Could this be from the medication?” And if we think it is, then we’ll potentially give them a break and then see if it goes away.

Audrey Sternberg: How does the safety profile of a treatment impact your choice of therapy?

Aaron Berger, MD: We certainly don’t want to give patients anything that we know has a high risk of adverse effects. The nice thing with all 3 of these medications is that the risk of significant adverse events is pretty low. With patients who have significant cardiovascular disease, like recent MI [myocardial infarction], recent congestive heart failure, treatments, things of that nature, we want to be cautious. There are some data in the trials that there may be some increased risk of cardiovascular events in these medications, especially for those high-risk patients. For patients who have very high-risk heart disease, cardiovascular disease, you may want to potentially delay the onset of treatment or discuss with their cardiologist. Although sometimes the cardiologist isn’t as familiar with these medications either, just like we’re not familiar with a lot of cardiovascular medications.

That’s an area of need moving forward: to get more resources available in terms of expertise to help us determine what’s safe for these patients with cardiovascular disease or neurologic disease, so we can help guide our patients better. Because we certainly don’t want to cause any harm. That’s obviously one of the major tenants of medicine: do no harm. We don’t want to cause harm, but the data on all these drugs are very clear as far as the benefit. The data also show that the adverse event profile for all 3 of these is pretty favorable overall, so it’s certainly worth giving it a try for patients unless they have some obvious contraindication.

In terms of who needs to be treated in general, if we’re not sure a patient really needs treatment, the other thing that we’re doing much more often now is genetic testing for patients who qualify. If they have a genetic mutation that may portend more high-risk cancer, those are patients you might want to start treatment earlier on rather than waiting until their PSA progresses further and their doubling time becomes faster. Those patients may have a more aggressive course depending on their genetic profile.

This transcript has been edited for clarity.

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