Darolutamide Demonstrates 31% Reduction in Death Risk for Nonmetastatic Castration-Resistant Prostate Cancer in NEJM-Published Phase 3 Trial

Recently, The New England Journal of Medicine (NEJM) published the overall survival and all other secondary endpoint results from the Phase 3 trial of darolutamide for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). The data showed that patients treated with darolutamide had a significantly improved survival rate, with a 31% reduction in the risk of death.

Screenshot source: New England Journal of Medicine

Darolutamide (Nubeqa) is an oral androgen receptor inhibitor (ARi) jointly developed by Bayer and Orion, which inhibits androgen receptor function and the growth of prostate cancer cells. It was approved for marketing by the U.S. FDA in July 2019. Currently, its marketing application in China has been included in the priority review by the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China.

In the “ARAMIS” trial, 1,509 male patients were randomized in a 2:1 ratio to receive darolutamide (n=955) or placebo (n=554) in addition to androgen deprivation therapy.

Previously reported trial results showed that the median metastasis-free survival in the darolutamide group was 40.4 months, significantly longer than the 18.4 months in the placebo group, thereby meeting the primary endpoint of the trial.

After confirming that the primary endpoint was positive, the trial was unblinded, and patients in the placebo group were allowed to cross over to receive darolutamide treatment. At the time of unblinding, all 170 patients still receiving placebo switched to darolutamide treatment; the 137 patients who had discontinued placebo prior to unblinding received at least one other therapy, most commonly docetaxel, abiraterone acetate, and enzalutamide.

The median follow-up period was 29.0 months. The latest published data show that the 3-year overall survival rates were 83% in the darolutamide group and 77% in the placebo group. The risk of death in the darolutamide group was significantly reduced by 31% compared with the placebo group.

▲Patients in the darolutamide group had significantly longer survival (Image source: Reference [1])

Darolutamide also demonstrated significant benefits in other secondary endpoints, including time to first symptomatic skeletal event and time to first use of cytotoxic chemotherapy. The incidence of adverse events was similar between the two groups, with no new safety signals observed.

The research team concluded that an overall survival benefit for patients in the darolutamide group was observed, even though more than half of the patients (55%) in the placebo group subsequently received darolutamide or other treatments.

References:

[1] Karim Fizazi, et al., (2020). Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med, DOI: 10.1056/NEJMoa2001342

[2] Darolutamide boosts survival in nonmetastatic prostate cancer. Retrieved September 16, 2020, from https://medicalxpress.com/news/2020-09-darolutamide-boosts-survival-nonmetastatic-prostate.html