Phase III ARAMIS Trial Showed Significant Improvement in OS for Patients with Prostate Cancer

The investigation of darolutamide plus ADT in men with non-metastatic castration-resistant prostate cancer indicated a significant improvement in overall survival in this patient population.

Results from the phase III androgen receptor inhibiting agent for metastatic-free survival (ARAMIS) trial that investigated darolutamide (Nubeqa) in men with non-metastatic castration-resistant prostate cancer (nmCRPC) showed a significant improvement in overall survival (OS) in patients receiving darolutamide plus androgen deprivation therapy (ADT) compared to placebo plus ADT, according to Bayer, the agent’s co-developer.

Details on the updated OS and other additional endpoints, as well as an update on longer term safety, are to be presented at an upcoming scientific meeting. 

Results from the trial previously reported showed a statistically significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS) of darolutamide plus ADT compared to placebo plus ADT, however OS data were not yet mature at the time of the MFS analysis. 

The FDA approved darolutamide on July 30, 2019 based on this randomized, double-blind, placebo-controlled, multi-center phase III study, which evaluated the safety and efficacy of the drug in patients with nmCRPC who were receiving a concomitant gonadotropin-releasing hormone analog or had a bilateral orchiectomy. 

In the study, a cohort of 1,500 patients were randomized 2:1 to receive 600 mg of darolutamide twice daily or placebo plus ADT. The primary efficacy endpoint was MFS, which was defined as the time from randomization to the time of first indication of blinded independent central review (BICR)-confirmed distant metastasis or death due to any cause within 33 weeks after the last evaluable scan, whichever transpired first. Darolutamide plus ADT demonstrated a statistically significant improvement in MFS, with a median MFS of 40.4 months versus 18.4 months with placebo plus ADT (HR = 0.41; 95% CI, 0.34, 0.50; < 0.0001). 

Clinically significant adverse reactions found in ≥2% of patients treated with the agent included ischemic heart disease (4% versus 3.4% on placebo) and heart failure (2.1% versus 0.9% on placebo). 

The agent has not been studied in women, and there is a warning and precaution for embryo-fetal toxicity. Men with female partners of reproductive potential are warned to use effective contraception during treatment and for 1 week after the last dose.

Adverse reactions that occurred more often in the darolutamide arm (≥2% over placebo) were fatigue (16% versus 11%), pain in extremity (6% versus 3%), and rash (3% versus 1%). Serious adverse reactions occurred in 25% of patients receiving the agent and in 20% of patients receiving placebo. Serious adverse reactions in ≥1% of patients who received darolutamide were urinary retention, pneumonia, and hematuria. 

Overall, 3.9% of patients receiving darolutamide and 3.2% of patients receiving placebo died from adverse reactions, including death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%) for darolutamide.

Darolutamide is an oral androgen receptor inhibitor that, in addition to the US, is approved in Brazil and Japan, and filings in the European Union and other regions are underway or planned. Darolutamide is currently only approved for the treatment of patients with nmCRPC.

A phase III study looking at the efficacy and safety of darolutamide in combination with standard ADT and docetaxel (Taxotere) in patients with metastatic hormone sensitive prostate cancer (ARASENS) is currently ongoing. The study population will consist of 1,300 subjects who will be randomized 1:1 to receive 600 mg of darolutamide or placebo twice daily with food, in addition to standard ADT and docetaxel. Participants will be stratified at randomization for the extent of disease and for Alkaline Phosphatase levels. 


NUBEQA® (darolutamide) Plus Androgen Deprivation Therapy Achieved the Secondary Endpoint of Overall Survival (OS) in Men with Non-Metastatic Castration-Resistant Prostate Cancer [news release]. Whippany, New Jersey. Published January 30, 2020. Accessed January 30, 2020.