Darolutamide Had Higher Number Needed to Harm in Non-Metastatic CRPC

A number needed to harm (NNH) analysis of second-generation androgen receptor inhibitors for non-metastatic castration-resistant prostate cancer (nmCRPC) showed a trend toward higher NNH for darolutamide compared with apalutamide and enzalutamide, according to a poster from the ASCO Quality Care Symposium.

All three drugs have been approved for the treatment of nmCRPC and offer both overall and metastasis-free survival benefit, but each has a different risk-benefit profile.

In this study, the researchers looked at data from relevant randomized clinical trials on adverse events that occurred in 5% or more of either arm. Data were taken from the ARAMIS trial of darolutamide, the SPARTAN trial of apalutamide, and the PROSPER trial of enzalutamide.

There was a trend of higher NNH for darolutamide in ARAMIS across all grades and grade 3-4 adverse events. According to the researchers, this indicates a lower likelihood of incremental harm across adverse events including fatigue, falls, hypertension, and fracture, compared with the two other drugs.

For example, looking at any grade falls, the NNH for darolutamide was 333.3 compared with 8.0 for apalutamide and 8.2 for enzalutamide. For grade 3/4 fatigue, the NNH was negative for darolutamide compared with 167.7 for apalutamide and 29.1 for enzalutamide.

Focusing on fatigue, falls and fractures, selection of darolutamide, which had the highest NNH, would result in 4,073 fewer all-grade fatigue events, 2,928 fewer falls, and 2,383 fewer fractures compared with apalutamide (falls) or enzalutamide (fatigue or fracture).

According to the poster, these findings “are noteworthy not only for patients, but also for healthcare systems considering the overall risk-benefit amongst these three androgen receptor inhibitors.”

Reference

Number Needed to Harm (NNH) in Patients With Non-Metastatic, Castration-Resistant Prostate Cancer (nmCRPC): A Final Analysis From the Darolutamide (D), Enzalutamide (E), and Apalutamide (A) Clinical Trials (Abstract 326)