Darolutamide/Docetaxel Granted FDA Priority Review for Metastatic Hormone-Sensitive Prostate Cancer


Trials results show darolutamide, docetaxel, and androgen deprivation therapy (ADT) reduced the risk of death by 32.5% versus docetaxel/ADT in patients with metastatic hormone-sensitive prostate cancer.

The FDA has granted priority review to a supplemental new drug application (sNDA) for darolutamide (Nubeqa) plus docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC).1

The application is based on findings from the phase 3 ARASENS trial (NCT02799602), which showed the combination of darolutamide, docetaxel, and androgen deprivation therapy (ADT) reduced the risk of death by 32.5% versus docetaxel/ADT (HR, 0.68; 95% CI, 0.57-0.80; < .001).2

The 4-year overall survival (OS) rate in the darolutamide cohort was 62.7% (95% CI, 58.7%-66.7%) compared with 50.4% (95% CI, 46.3%-54.6%) in the control arm.

“Bayer remains dedicated to addressing unmet needs in prostate cancer treatment for various stages of the disease,” said Christine Roth, member of the executive committee of the Pharmaceutical Division and head of the Oncology SBU at Bayer, in a press release. “Today’s sNDA acceptance, confirmation of priority review and participation in Project Orbis, bring us closer to adding a new indication for [darolutamide] in combination with docetaxel to benefit men with mHSPC.”

The international, double-blind, placebo-controlled, phase 3 ARASENS trial enrolled patients with histologically or cytologically confirmed prostate cancer. To be eligible, patients must have been at least 18 years of age, have an ECOG performance status of 0 to 1, and be candidates for ADT and docetaxel administration per investigator judgment.

Patients with regional lymph-node involvement only or who were administered ADT more than 12 weeks prior to randomization were excluded. Patients also could not have received androgen-receptor pathway inhibitors, chemotherapy, or immunotherapy prior to randomization, and they could not have been administered radiotherapy within 2 weeks prior to randomization.

Within 12 weeks before randomization, all study patients were administered ADT or underwent orchiectomy. Patients received docetaxel at a dose of 75 mg/m2 on day 1 of each 21-day cycle for 6 cycles. Prednisone or prednisolone was administered per investigator discretion and started within 6 weeks before randomization.

Patients (n = 1306) were randomized 1:1 to receive either darolutamide at 600 mg twice daily (n = 651) or matched placebo (n = 655). Participants were administered treatment until progressive disease, a change in antineoplastic therapy, unacceptable toxicity, patient of physician decision, death, or nonadherence.

OS was the primary end point for the trial, with key secondary end points including time to castration-resistant disease, time to pain progression, symptomatic skeletal event-free survival, time to a first symptomatic skeletal event, time to initiation of subsequent systemic antineoplastic therapy, time to worsening of disease-related physical symptoms, time to initiation of opioid treatment for 7 or more consecutive days, and safety.

The median age of patients was 67 years and most had an ECOG performance status of 0 (71%), 78.2% had a Gleason score of 8 or higher, and approximately 86% had metastatic disease at the time of diagnosis. All patients had metastatic disease at baseline, whereas 79.5% had bone metastases and 17.5% had visceral metastases.

The trial found adding darolutamide to docetaxel/ADT produced improved time to development of castration-resistant disease compared with docetaxel/ADT alone (HR, 0.36; 95% CI, 0.30-0.42; < .001).

Further, the study found that time to pain progression (HR, 0.79; 95% CI, 0.66-0.95; = .01), symptomatic skeletal event-free survival (HR, 0.61; 95% CI, 0.52-0.72; < .001), time to first symptomatic skeletal event (HR, 0.71; 95% CI, 0.54-0.94; = .02), and time to the initiation of subsequent systemic antineoplastic therapy (HR, 0.39; 95% CI, 0.33-0.46; < .001) was enhanced with the addition of darolutamide.

Any-grade toxicities were experienced by 99.5% of patients in the investigative cohort who were included in the safety analysis set compared with 98.9% of patients in the control group. Adverse effects (AEs) were grade 3 or higher in 70.2% in the investigative cohort and 67.5% in the control group. Serious AEs were experienced by 44.8% of patients in the darolutamide cohort compared with 42.3% of patients in the control cohort.

Further, 13.5% of patients administered darolutamide had toxicities that resulted in permanent treatment discontinuation compared 10.6% of patients in the placebo cohort. Docetaxel was permanently discontinued in 8.0% of patients in the investigative cohort compared with 10.3% of patients in the control group.


  1. US FDA accepts supplemental new drug application (sNDA) and grants priority review for NUBEQA (darolutamide) in combination with docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC). News release. Bayer. May 3, 2022. Accessed May 3, 2022. https://bit.ly/3LE5rAg
  2. Smith MR, Hussain M, Saad F, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022;386(12):1132-1142. doi:10.1056/NEJMoa2119115
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