The Efficacy of Darolutamide for Non Metastatic Castration-Resistant Prostate Patients

In July 2019, darolutamide became the newest available oral androgen receptor inhibitor approved by the FDA for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC) patients. The Phase 3 ARAMIS trial evaluated darolutamide with androgen deprivation therapy (ADT) versus ADT plus placebo for nmCRPC patients and demonstrated significant improvement in metastasis-free survival (MFS), extending MFS to 40 months for those treated with darolutamide as opposed to 18 months for patients randomized to the ADT + placebo arm.


Novel approaches for the treatment of nmCRPC are now NCCN recommended, as the preferred approach to thwart prostate cancer progression for nmCRPC patients. With the awareness of a rising PSA with castrate levels of testosterone, and a lack of metastases with CT and Bone scan imaging, novel oral AR inhibitors will improve MFS., thus the importance of routine and appropriate PSA monitoring with attendant radiographic imaging. Darolutamide’s approval, licensed with the commercial name, Nubeqa, provides the arrival of another important therapeutic option for extending MFS in nmCRPC patients.

The Phase 3 ARAMIS trial was a global randomized trial consisting of 1509 nmCRPC patients; its positive results led to the inclusion of darolutamide in the standard of care repertoire for the treatment of nmCRPC. At ASCO GU 2019, Karim Fizazi, MD, Ph.D., sat down with Alicia Morgans, MD, MPH to discuss the results of ARAMIS. They discussed how the use of darolutamide showed a robust safety profile, few drug-drug interactions, and a paucity of serious adverse event side effects. The trial results and darolutamide’s FDA approval have initiated numerous additional advanced prostate cancer trials.

An insightful conversation on ARAMIS from ASCO GU 2019 was an interview between Petros Grivas, MD, Ph.D. and Neeraj Agarwal, MD. Agarwal commented on the practice-changing nature of the study and Karim Fizazi’s presentation of ARAMIS at ASCO GU 2019. Agarwal comments that the result of an almost 22-month extension of MFS is impressive. He notes that the drugs unique mode of action with the benefit of minimal penetration across the blood brain barrier has very positive avoidance of central nervous system side effects, which has been reported with other approved nmCRPC therapies.

The recent success of Darolutamide builds off of landmark trials such as SPARTAN and PROSPER which investigated the efficacy of apalutamide and enzalutamide respectively for patients with nmCRPC. Comparing the three trials, one can ascertain differences in efficacy endpoints, mild inclusion criteria differences, and common adverse events reported. Direct comparator trials have not yet been reported. Of note, darolutamide has a unique molecular structure as an oral androgen receptor inhibitor. In conclusion, the positive results of the three nmCRPC trials have clearly augmented the treatment armamentarium for the benefit of nmCRPC patients.

Looking forward to the new year, the recent advancements in the nmCRPC disease space, as well as metastatic castration sensitive prostate cancer (mCSPC), should inspire ongoing and additional trials to amplify benefits for advanced prostate cancer patients. As ARAMIS was an important part of the nmCRPC narrative in 2019, its promising efficacy and tolerability will hopefully present physicians, researchers, and patients with additional therapeutic approaches within the prostate cancer continuum.

Written by: Neal Shore, MD, FACS, Medical Director of the Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, South Carolina

Published Date: January 20th, 2020

Further Related Content:
Read: Darolutamide: Approved For Non-Metastatic Castration-Resistant Prostate Cancer
Read: ARAMIS: Efficacy and Safety of Darolutamide in nmCRPC | ASCO GU 2019
Watch: ARAMIS Trial in Prostate Cancer: Impact of Darolutamide on Pain and Quality of Life - Karim Fizazi