Darolutamide Plus Docetaxel/ADT Significantly Improves OS in Metastatic Hormone-Sensitive Prostate Cancer

Scott Z. Fields, MD

The addition of darolutamide (Nubeqa) to docetaxel and androgen deprivation therapy (ADT) resulted in a significant improvement in overall survival (OS) compared with docetaxel/ADT alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC), meeting the primary end point of the phase 3 ARASENS trial (NCT02799602).¹

Detailed findings from the trial will be shared at an upcoming medical meeting, according to Bayer.

“For patients with mHSPC, there remains a significant need for new therapeutic approaches that improve treatment outcomes. ARASENS was prospectively designed to investigate whether combining [darolutamide] with docetaxel and ADT could lead to an increase in OS for men with mHSPC,” Scott Z. Fields, MD, senior vice president and head of the Oncology Department of the Pharmaceutical Division at Bayer, stated in a press release. “We are especially grateful to the patients and investigators for participating in this important trial and look forward to presenting the full results at an upcoming meeting.”

The multicenter, double-blind, placebo-controlled, phase 3 trial enrolled patients who were at least 18 years of age who had historically or cytologically confirmed adenocarcinoma of the prostate, documented metastatic disease, an ECOG performance status of 0 or 1, and acceptable bone marrow, liver, and renal function.² Patients needed to be eligible for ADT and docetaxel, and they had to have started treatment with ADT with or without a first-generation androgen therapy 12 weeks or less before randomization.

If patients received previous treatment with a LHRH agonist/antagonist, a second-generation androgen receptor inhibitor, CYP17 enzyme inhibitors, chemotherapy, or immunotherapy for their disease prior to randomization, they were excluded. Moreover, patients who received prior radiotherapy or radiopharmaceuticals within 2 weeks before randomization, or who had stroke, myocardial infarction, severe or unstable angina pectoris, coronary or peripheral artery bypass graft, or congestive heart failure within 6 months prior to randomization, they were also excluded.

A total of 1306 newly diagnosed patients were randomized 1:1 within 12 weeks of starting ADT to receive either darolutamide at 600 mg twice daily or matching placebo, both in addition to ADT plus docetaxel, as prescribed by the treating physician. Patients were stratified based on disease extent and alkaline phosphatase level.

The primary end point was to demonstrate the superiority of darolutamide vs placebo, both in combination with ADT and docetaxel, in terms of OS. Key secondary end points included time to castration-resistant disease, time to initiation of subsequent antineoplastic therapy, symptomatic skeletal event-free survival (SSE-FS), time to first SSE, time to initiation of opioid use, time to pain progression, and time to worsening of physical disease symptoms.

Bayer shared plans to discuss the data from the trial with global health authorities as they relate to submission of darolutamide for marketing authorization in this indication.

References

1. 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. News release. Bayer; December 3, 2021. Accessed December 3, 2021. https://bit.ly/3DjUnTR
2. Smith MR, Saad F, Hussain M, et al. ARASENS: a phase 3 trial of darolutamide in combination with docetaxel for men with metastatic hormone-sensitive prostate cancer (mHSPC). J Clin Oncol. 2018;36(suppl 6S):TPS383. doi:10.1200/JCO.2018.36.6_suppl.TPS383