First Real-World Data on Second-Generation AR Inhibitor Use in nmCRPC


A review of real-world data from the DEAR study of darolutamide, enzalutamide and apalutamide for the treatment of nonmetastatic castration-resistant prostate cancer is given by Alicia Morgans, MD, MPH.

In season 4, episode 14 of Targeted Talks, Alicia Morgans, MD, MPH, medical director of the Survivorship Program, physician at Dana-Farber Cancer Institute, and associate professor of Medicine, Harvard Medical School, discusses comparative real-world data from the DEAR study of darolutamide (Nubeqa), enzalutamide (Xtandi), and apalutamide (Erleada) for the treatment of United States-based patients with nonmetastatic castration-resistant prostate cancer (nmCRPC).

DEAR was the first study to evaluate the real-world utilization of the second-generation androgen receptor (AR) inhibitors in patients with nmCRPC. According to results presented at the American Society of Clinical Oncology Annual Meeting in June 2023, fewer patients with nmCRPC who received darolutamide experienced discontinued initial AR inhibitor treatment or progressed to metastasis (DIS/MET) versus patients treated with enzalutamide and apalutamide. Further, time to DIS/MET was longer for patients treated with darolutamide.1

At a median follow-up of 18.4 months in the darolutamide arm, 19.7 in the enzalutamide arm, and 21.4 months in the apalutamide arm, the percentage of patients with DIS/MET events was 35.9%, compared with 52.1%, and 50.9%, respectively.

“There were also lower rates in terms of reasons for discontinuation of progression to mCRPC for patients who were treated with darolutamide when compared with those patients treated with enzalutamide and apalutamide. This is a numeric comparison, and there was not a statistical test performed to actually formally compare these though,” says Morgans.

The overall takeaway from this real-world research is that darolutamide is a very specific AR inhibitor and has low potential for crossing the blood-brain barrier.

“When we looked, additionally, at this progression to mCRPC we saw that the proportion of patients with progression to mCRPC was lower among patients treated with darolutamide than among patients treated with apalutamide or enzalutamide. And this was assessed in a formal statistical comparison in both unadjusted and adjusted analyses,” explains Morgans.


George DJ, Khan N, Constantinovici N, et al. Real-world use of darolutamide, enzalutamide, and apalutamide for non-metastatic castration-resistant prostate cancer (DEAR). J Clin Oncol. 2023;41(suppl 6). doi: 10.1200/JCO.2023.41.6_suppl.332

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