FDA Launches Priority Review of Darolutamide for Metastatic Hormone-Sensitive Prostate Cancer


The FDA has granted a priority review designation to darolutamide plus docetaxel for patients with metastatic hormone-sensitive prostate cancer.

Following the submission of new drug application (sNDA), the FDA will conduct a priority review of darolutamide (Nubeqa) plus docetaxel for patients with metastatic hormone-sensitive prostate cancer (mHSPC).1

The application is supported by findings from the phase 3 ARASENS trial (NCT02799602), in which the combination of darolutamide, docetaxel, and androgen deprivation therapy (ADT) resulted in a 32.5% reduction in the risk of death compared with docetaxel/ADT (HR, 0.68; 95% CI, 0.57-0.80; < .001).2 The 4-year overall survival (OS) rate in the darolutamide arm was 62.7% (95% CI, 58.7%-66.7%) vs 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,” Christine Roth, member of the executive committee of the Pharmaceutical Division and head of the Oncology SBU at Bayer, stated 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.”

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

Patients who had regional lymph-node involvement only or who received ADT more than 12 weeks before randomization were excluded. Patients also could not have received androgen-receptor pathway inhibitors, chemotherapy, or immunotherapy for their disease before randomization, nor could they have received radiotherapy within 2 weeks before randomization.

Within 12 weeks before randomization, all study participants received ADT or underwent orchiectomy. They were also administered docetaxel at a dose of 75 mg/m2 on day 1 of every 21-day cycle for 6 cycles, and prednisone or prednisolone, which was given per investigator discretion and started within 6 weeks prior to randomization.

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

Participants were stratified based on stage of metastasis (nonregional lymph-node metastases only vs bone metastases with or without lymph-node metastases vs visceral metastases with or without lymph-node or bone metastases) and alkaline phosphatase level (below the upper limit of normal [ULN] vs able the ULN).

OS served as the primary end point for the research, and key secondary end points comprised 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 full analysis set was comprised of 1305 patients, 651 of whom were on the darolutamide arm and 654 of whom were on the control arm.

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

Additional findings published in the New England Journal of Medicine showed that the addition of darolutamide to docetaxel/ADT resulted in improved time to development of castration-resistant disease vs docetaxel/ADT alone (HR, 0.36; 95% CI, 0.30-0.42; < .001).

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 also improved with the addition of darolutamide.

Regarding safety, any-grade toxicities were experienced by 99.5% of the 652 patients in the investigative arm included in the safety analysis set, vs 98.9% of the 650 patients in the control arm; effects were grade 3 or higher in 70.2% and 67.5% of patients, respectively. Serious adverse effects (AEs) were experienced by 44.8% of those in the darolutamide arm vs 42.3% of those in the control arm.

Select grade 3 or 4 AEs of interest that were noted in the investigative arm included neutropenia (33.7%), febrile neutropenia (7.8%), hypertension (6.4%), anemia (4.8%), pneumonia (3.2%), hyperglycemia (2.8%), alanine aminotransferase increase (2.8%), aspartate aminotransferase increase (2.6%), and weight increase (2.1%).

Moreover, 13.5% of those who received darolutamide experienced toxicities that resulted in permanent treatment discontinuation vs 10.6% of those who received placebo. Docetaxel was permanently discontinued in 8.0% of those in the investigative arm and 10.3% of those in the control arm.

In March 2022, a Variation Type II application was also submitted to the European Medicines Agency seeking the approval of darolutamide plus docetaxel in patients with mHSPC.That application is also supported by findings from ARASENS. Additional global submissions in mHSPC are underway, according to Bayer.


  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
  3. Bayer submits applications in the US and EU for additional indication of NUBEQA (darolutamide). News release. Bayer; March 9, 2022. Accessed May 3, 2022. https://bit.ly/3CrqSAW

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