Real-World Data Detail Potential Benefits of Darolutamide Over Other ARIs in nmCRPC

Alicia K. Morgans, MD, MP

Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) who received darolutamide (Nubeqa) were observed to have a longer time to treatment discontinuation and progression to metastatic castration-resistant disease than those who received enzalutamide (Xtandi) or apalutamide (Erleada), according to real-world findings from the DEAR study (NCT05362149) presented at the 2023 ASCO Annual Meeting.

“There is limited real-world evidence on androgen receptor inhibitor [ARI] discontinuation, the underlying reasons for discontinuation, the incidence of adverse events or AEs, and disease progression for different ARIs,” said Alicia K. Morgans, MD, MPH, lead study author and a genitourinary medical oncologist and medical director of the Survivorship Program at the Dana-Farber Cancer Institute, in Boston, Massachusetts. “DEAR is the first real-world study using a single data source to compare utilization, outcomes, and incidence of AEs for the 3 ARIs currently approved for the treatment of nonmetastatic CRPC.”

For the study, the investigators included adult men who received a diagnosis of nmCRPC and who initiated an ARI therapy for the first time during the patient identification period.

The investigators analyzed the proportion of patients who discontinued initial ARI treatment and the reasons for discontinuation, proportion of patients who progressed to mCRPC, time to initial ARI discontinuation, time to progression to mCRPC, and incidence of AEs.

A total 870 men were included in the study, 362 of whom received treatment with darolutamide, 382 with enzalutamide, and 126 with apalutamide. Morgans reported that “observed demographics, baseline characteristics, and duration of follow-up were similar across the 3 treatment cohorts.” The time from diagnosis of prostate cancer to the index date, as well as the time from nmCRPC diagnosis to the index date were found to vary slightly across the 3 cohorts.

The proportion of patients who discontinued initial ARI treatment was 30.4% for darolutamide compared with 40.8% for enzalutamide and 46.0% for apalutamide.

“A Cox proportional hazards model adjusting for baseline factors showed that patients on darolutamide had a 27.4% lower risk of discontinuing initial ARI treatment over time compared with enzalutamide and a 39.1% lower risk compared with apalutamide,” Morgans said.

AEs were the most common reason for nmCRPC treatment discontinuation, occurring in 10.2% of patients receiving darolutamide, 14.4% of patients receiving enzalutamide, and 15.1% of patients receiving apalutamide.

The investigators also reported that the proportion of patients who progressed to mCRPC was lower with darolutamide (17.7%) compared with enzalutamide (28.3%) and apalutamide (27.8%). In addition, a Cox proportional hazards model that adjusted for baseline factors indicated that patients receiving darolutamide had a 40.6% lower risk of progression to mCRPC over time vs enzalutamide and a 35.3% lower risk of progression to mCRPC vs apalutamide.

In all, 24.9% patients receiving darolutamide experienced any AE vs 29.3% and 30.2% of patients receiving enzalutamide and apalutamide, respectively.

Limitations of the study discussed by Morgans included the fact that although the analysis adjusted for observed differences in baseline characteristics among the treatment cohorts, “unobserved confounding factors that may influence treatment duration and clinical outcomes in the absence of randomization,” according to Morgans. Another limitation is the ability to generalize the results to other patient populations.

“Future studies are needed to confirm these results in other populations or using other data sources,” Morgans said.

“In conclusion, darolutamide was associated with a longer time to treatment discontinuation and a longer time to progression to mCRPC compared with enzalutamide and apalutamide in a real-world setting,” she added.

Reference

Morgans AK, Shore ND, Khan N, et al. Comparative real-world (RW) evidence on darolutamide (Daro), enzalutamide (Enza), and apalutamide (Apa) for patients (Pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in the United States: DEAR. J Clin Oncol. 2023;41(suppl 16):5097. doi:10.1200/JCO.2023.41.16_suppl.5097