Study: Darolutamide, Docetaxel, Androgen Deprivation Therapy Increases Overall Survival in Metastatic Hormone-Sensitive Prostate Cancer

The phase 3 ARASENS trial is the only study prospectively designed to evaluate an androgen receptor inhibitor combined with docetaxel and androgen deprivation therapy in this patient population.

The phase 3 ARASENS trial met its primary endpoint of overall survival (OS) for the combination of darolutamide, docetaxel, and androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC), according to a press release from Bayer.

Darolutamide is an androgen receptor inhibitor (ARi) with a distinct chemical structure that inhibits androgen binding, androgen receptor translocation, and androgen receptor-mediated transcription. It is indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer.

Detailed results from the ARASENS trial are expected to be presented at an upcoming scientific congress. Darolutamide is currently indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer.

The ARASENS trial is the only phase 3 randomized, multi-center, double-blind trial that was prospectively designed to evaluate the efficacy and safety of an androgen receptor inhibitor combined with docetaxel and ADT compared to docetaxel and ADT in patients with mHSPC.

“For patients with mHSPC, there remains a significant need for new therapeutic approaches that improve treatment outcomes,” said Scott Z. Fields, MD, senior vice president and head of oncology development at Bayer’s Pharmaceutical Division, in the press release. “ARASENS was prospectively designed to investigate whether combining Nubeqa with docetaxel and ADT could lead to an increase in overall survival for men with mHSPC.”

In the trial, 1306 newly diagnosed patients were randomized 1:1 to receive 600 mg of darolutamide twice a day or matching placebo, in addition to docetaxel and standard ADT. The primary endpoint was OS, and secondary endpoints included time to castration-resistant prostate cancer, time to initiation of subsequent anticancer therapy, time to first symptomatic skeletal event, and time to pain progression. All of the endpoints and adverse events (AEs) were measured at 12-week intervals.

Serious AEs occurred in 25% of patients receiving darolutamide and in 20% of patients receiving placebo. AEs in 1% or more of patients included urinary retention, pneumonia, and hematuria.

Overall, 3.9% of patients receiving darolutamide and 3.2% of patients receiving placebo died from AEs, which included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%) in the darolutamide group.

Furthermore, AEs occurring more frequently in the darolutamide arm—defined as 2% or more than in the placebo arm—included fatigue, pain in extremity, and rash. Clinically significant AEs occurring in ≥2% of patients treated with darolutamide included ischemic heart disease and heart failure.

REFERENCE

Phase II investigational trial of Nubeqa (darolutamide) in combination with docetaxel and androgen deprivation therapy (ADT) meets primary endpoint of significantly increasing overall survival (OS) in patients with mHSPC. News release. Bayer; December 3, 2021. Accessed January 17, 2022. https://bayer2019tf.q4web.com/news/news-details/2021/Phase-III-Investigational-Trial-of-NUBEQA-darolutamide-in-Combination-with-Docetaxel-and-Androgen-Deprivation-Therapy-ADT-Meets-Primary-Endpoint-of-Significantly-Increasing-Overall-Survival-OS-in-Patients-with-mHSPC/default.aspx