Darolutamide Demonstrates Favorable Tolerability, Decreased Metastatic Progression in nmCRPC

Daniel J. George, MD

Treatment with darolutamide (Nubeqa) decreased the likelihood of developing metastatic disease or discontinuing treatment because of adverse effects (AEs) vs treatment with apalutamide (Erleada) or enzalutamide (Xtandi) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC), according to findings from the DEAR study that were presented at the 2023 Genitourinary Cancers Symposium.

“The real-world evidence study reinforces the favorable safety profile of darolutimide in the ARAMIS study population,” said Daniel J. George, MD, professor of medicine and of surgery at Duke University School of Medicine in Durham, North Carolina, during the presentation. “It further demonstrates the importance of treatment tolerability and the potential for longer treatment duration with darolutamide compared to enzalutamide and apalutamide, which may in turn improve treatment outcomes.”

Researchers conducting the DEAR study compared three second-generation androgen receptor inhibitors, which are considered the current preferred treatment option for nmCRPC. This comparison was done to determine real-world utilization of the drugs and examine the incidence of AEs, which are the leading cause of treatment discontinuation for androgen receptor inhibitors.

Researchers assessed electronic medical records of 828 patients with nmCRPC. Patients were divided into 3 cohorts based on treatment: darolutamide (n = 340; median age, 80 years), enzalutamide (n = 367; median age, 79 years), and apalutamide (n = 121; median age, 80 years).

Treatment discontinuation or progression to metastatic disease occurred in 37% of patients (n = 340) treated with darolutamide compared with 51% (n = 187) of patients treated with enzalutamide and 51% (n = 62) of those treated with apalutamide. The median time to discontinuation or progress to metastatic disease was not reached in the darolutamide group (95% CI, 30.1-NA). In contrast, these events occurred at a median of 23.1 months (95% CI, 18.2-26.4) in the enzalutamide group and 20.5 months (95% CI, 12.3-27.2) in the apalutamide group.

The most common reasons for treatment discontinuation included AEs, progression to metastatic disease or death, and switching to another androgen receptor inhibitor. George noted that a lower proportion of patients in the darolutamide experienced these events compared with the other two groups.

In particular, AEs occurred in 9.7% of patients in the darolutamide cohort, 14.4% in the enzalutamide cohort and 15.7% in the apalutamide cohort. Progression to metastatic disease or death was observed in 8.8% of patients treated with darolutamide, 12% in those treated with enzalutamide and 13.2% in patients treated with apalutamide.

Study authors posit the favorable outcomes in patients treated with darolutamide may be attributed to “to darolutamide being a structurally distinct (androgen receptor inhibitor) with low potential for blood–brain barrier penetration,” the researchers wrote in the abstract.

Reference

George DJ, Khan N, Constantinovici N, et al. Real-world use of darolutamide, enzalutamide, and apalutamide for non-metastatic castration-resistant prostate cancer (DEAR). Presented at: 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium; February 16-18, 2023; San Francisco, CA. Abstract 332.