#darolutamide

Long-Term Darolutamide Displays Favorable Safety Profile in Patients With mCRPC

Patients with metastatic castration-resistant prostate cancer treated with darolutamide for more than 4 years tolerated well the adverse effects of the drug. Patients with metastatic castration-resistant prostate cancer (mCRPC) treated with darolutamide (Nubeqa) for more than 4 years tolerated well the adverse effects (AEs) of the drug. These extended darolutamide safety and tolerability results…

In a subgroup analysis of the pivotal phase 3 ARAMIS trial, it was shown that the efficacy of darolutamide (Nubeqa) was sustained in men who experience a rapid PSA doubling time. 

The analysis demonstrated that Darolutamide (Nubeqa) is effective in treating men who have prostate cancer who are at high-risk but are non-metastatic and castration-resistant (nmCRPC)and who have a fast PSA doubling time (PSADT) between 6 and 10 months. This subgroup analysis was presented during the 2020 European Association of Urology Virtual Congress.1

The analysis showed that among men with a PSADT ≤6 months, darolutamide reduced the risk of developing metastases or death by 59% versus placebo. This benefit with Nubeqa was similar to that observed in men with a PSADT >6 months, in whom there was a 62% reduction in the risk of metastases or death. 

The safety profile for darolutamide was similar between the two populations. 

“These results tell us that men who have a PSADT between 6 and 10 months can also benefit from Nubeqa without increased safety risk,” said lead study author Martin Bögemann, MD, Münster University Medical Center, Department of Urology, Münster, Germany.

Since these men who have non-metastatic CRPC with a PSADT ≤6 months are at the highest risk of metastatic progression, this is good news. 

This post is in Advance of Full Data Being Released by Bayer.

Results from the final overall survival analysis of the Phase III ARAMIS (Androgen Receptor inhibiting Agent for MetastatIc-free Survival) trial that investigated Nubeqa® (aka darolutamide) in men with non-metastatic castration-resistant prostate cancer (nmCRPC) show a significant improvement in their overall survival (OS) (they lived longer) in men receiving Nubeqa plus androgen deprivation therapy (ADT) compared to men receiving a placebo plus the standard of care, ADT.

Results of ARAMIS that was previously published showed a statistically significant improvement in men’s ability to delay the development of metastasis, or of metastasis-free survival (MFS) when they took darolutamide plus ADT compared to placebo plus ADT. When these results were published the overall survival (OS) (how long a man lived) data were not yet mature and could not be evaluated. 

Detailed data on the updated OS and other additional endpoints, as well as an update on longer-term safety, will be presented at an upcoming ASCO- GU Conference.

We are happy to announce that on July 30, 2019, the Food and Drug Administration (FDA) approved a new drug, darolutamide (NUBEQA®, Bayer HealthCare Pharmaceuticals Inc.) for the treatment of men with non-metastatic castration-resistant prostate cancer.

The approval was based on the clinical trial called ARAMIS (NCT02200614), a multicenter, double-blind, placebo-controlled clinical trial in 1,509 men with non-metastatic castration resistant prostate cancer.

The men were randomized (2:1) to receive either 600 mg darolutamide orally twice daily (n=955) or placebo (n=554). In addition to the darolutamide, the men received a gonadotropin-releasing hormone (GnRH) analog (like Lupron) concurrently or had a previous orchiectomy.

The trial’s primary endpoint was metastasis free survival (MFS), defined as the time from randomization to the first evidence of distant metastasis or death from any cause within 33 weeks after the last evaluable scan, whichever occurred first.

The median MFS was 40.4 months for men treated with darolutamide compared with 18.4 months for those receiving placebo. The overall survival (OS) data had not matured.

The most common adverse reactions (≥2%) in the men who received darolutamide were fatigue, pain in their extremities, and rash. Ischemic heart disease (4.3%) and heart failure (2.1%) were more common on the men receiving darolutamide. The seizure incidence was similar in the two arms (0.2%).

The FDA has recommended that the darolutamide dose is 600 mg (two 300 mg tablets) administered orally twice daily with food. Men should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

The ARAMIS trial evaluated the investigational treatment darolutamide.  The trial showed great results including delaying the initial onset (actually the visualization by current scanning technology) of metastatic disease in prostate cancer.  

In addition, ARAMIS showed that darolutamide increased overall survival for men with prostate cancer, it delayed the time to the use of cytotoxic chemotherapy as well as improving the important quality of life (QoL) measures of time to pain progression, and time to developing a symptomatic skeletal-related event.  

The incidence of adverse events that occurred or worsened during the treatment period as well as the incidence of men dropping out of the trial was also similar between the investigation and the control arms of the trial.  

Also, notable, the trial showed that darolutamide was not associated with a higher incidence of seizures, falls, fractures, cognitive disorder, or hypertension than placebo, a problem for similar drugs in the M0 space. 

Overall, patient-reported quality of life was similar in the darolutamide group and placebo group. 

MedicalResearch.com Interview with:

For men with non-metastatic castrate resistant prostate cancer (nmCRPC) delaying the development of metastases while minimizing the risk of adverse events, is an important treatment goal.

At the recent ASCO GU conference, we learned the results from the ARAMUS phase III trial which evaluated Darolutamide, an androgen receptor (AR) antagonist (a drug that prevents androgens from affecting prostate and prostate cancer cells). The trial studied the efficacy and safety of darolutamide in men with nmCRPC men.

The trial was a double-blind, placebo-controlled phase III trial that randomized nmCRPC men in a 2:1 ratio to receive darolutamide 600 mg (two 300 mg tablets) twice daily or placebo, while they continued androgen deprivation therapy (ADT).

The primary endpoint of the trial was metastasis-free survival (MFS), with independent central review of radiographic imaging every 16 weeks. Secondary endpoints include overall survival (OS), time to pain progression first use of cytotoxic chemotherapy and first symptomatic skeletal event, as well as a safety profile.

The trial, which evaluated 1,509 men showed:

1- Median MFS was 40.4 months with darolutamide vs. 18.4 months with placebo.

2- Overall survival showed a trend in favor of darolutamide.

3- Time to pain progress also showed a trend in favor of darolutamide over placebo.

4- Other secondary and exploratory efficacy endpoints also favored darolutamide.

The noted incidences of treatment adverse events (AEs) and discontinuation of therapy were comparable between darolutamide and the placebo arms;

Conclusion: Among men with nmCRPC, metastasis-free survival was significantly longer with darolutamide than with placebo along with a low incidence of treatment-related adverse events.

Darolutamide is not approved by the FDA. For it to be considered for approval, the data will need to be submitted to the FDA. The other androgen receptor antagonists that are currently FDA approved in the same space are bicalutamide (Casodex), apalutamide (Erleada) and enzalutamide (Xtandi).

Clinical trial information: NCT02200614