Understanding ARPIs to Make Therapy Selection in Prostate Cancer

Pedro C. Barata, MD, MSc, associate professor of medicine at Case Western University and director of the Clinical Genitourinary Medical Oncology Research Program at University Hospitals Seidman Cancer Center in Cleveland, Ohio, discusses the advantages and disadvantages of darolutamide (Nubeqa) in metastatic hormone-sensitive prostate cancer (mHSPC).

Darolutamide has a favorable safety profile and low potential for drug-drug interactions (DDIs) in the androgen receptor pathway inhibitor (ARPI) space, according to Barata. He notes preclinical and clinical data suggesting darolutamide has a lower risk of crossing the blood-brain barrier, leading to fewer adverse events like dizziness, fractures, and mental fogginess.

Despite the need for twice-daily dosing and the lack of generic therapy being a barrier for some patients, Barata considers darolutamide a good option in clinical practice for treating prostate cancer.

TRANSCRIPTION

0:10 | I think the efficacy is absolutely confirmed for darolutamide and the other ARPIs, to be quite honest with you. I think the safety profile is relevant. When you look at the different safety profiles, I really think that darolutamide has a very favorable safety profile when you look at things like DDIs, including anticoagulation, etc. Darolutamide has a low potential for relevant DDIs with drugs that inhibit CYP and so from that point of view, that's an advantage; that's a drug advantage in that class of agents.

0:59 | I also think that the data out there, preclinical data or [laboratory] data rather, suggesting that has less cross blood-brain barrier. Clinically, it's possible that [could] be the case by the lower number of dizziness and fractures and falls and mental fogginess. Then we compare to placebo, it's very similar to placebo from that perspective. We can look at trials like ARAMIS [NCT02200614], for example, where patients don't have disease that you see on conventional scans, and you can actually appreciate not a huge difference compared to placebo. So to me, that's an advantage of darolutamide.

1:50 | [A] disadvantage is you take it twice a day, granted, with or without food. To me, that's the major disadvantage, and the fact that there's still not a generic therapy, so perhaps for some patients that might be a barrier, and we need to be aware of that. But the list of advantages is relevant, as I mentioned. So that balance is relevant. We always do that in clinical practice. Certainly, it is one of my preferred options in practice when I'm talking about patients with prostate cancer and I'm considering an ARPI.