FDA Grants Priority Review to Darolutamide Plus Docetaxel for mHSPC


The FDA has accepted a supplemental new drug application for darolutamide in combination with docetaxel for the treatment of metastatic hormone-sensitive prostate cancer and granted it priority review.

The FDA has accepted a supplemental new drug application (sNDA) for darolutamide (Nubeqa) in combination with docetaxel for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) and granted it priority review, according to a press release by Bayer.1

Results from the ARASENs clinical trial support the sNDA for darolutamide plus docetaxel. In the study, the combination plus androgen deprivation therapy (ADT) showed a statistically significant improvement in overall survival (OS) compared with docetaxel and ADT alone.

The median OS was not evaluable (NE) in the darolutamide arm compared with 48.9 months (95% CI, 44.4-NE) in the ADT arm (HR, 0.68l 95% CI, 0.57-0.80; P <.001). The OS benefit was observed despite many patients having received subsequent life-prolonging systemic therapies. At the 4-year mark, the OS rate with darolutamide was 62.7% (95% CI, 58.7%-66.7%) compared with 50.4% (95% CI, 46.3%-54.6%) in the control arm. OS was also favorable across most of the subgroups evaluated in the study.

“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. “Today’s sNDA acceptance, confirmation of priority review and participation in Project Orbis, bring us closer to adding a new indication for Nubeqa in combination with docetaxel to benefit men with mHSPC.”

ARASENs is a randomized, double-blind, placebo-controlled phase 3 study (NCT02799602) of 1,306 patients.2 The patients were randomized 1:1 to receive either darolutamide 600 mg twice daily with food in combination with standard ADT and docetaxel or standard ADR with docetaxel and placebo. These patients were assessed for the primary end point of OS as well as secondary end points including time to castration resistant prostate cancer, time to initiation of subsequent antineoplastic therapy, symptomatic skeletal event-free survival (EFS), time to first symptomatic skeletal event, time to initiation of opioid use, time to pain progression, time to worsening of physical symptoms of disease, and the number of patients with adverse events (AEs).3

Results for the secondary study end points showed that time to castration-resistant prostate cancer was significantly longer with darolutamide treatment compared with the control (HR, 0.36; 95% CI, 0.30-0.42; P <.001). Symptomatic skeletal EFS was also extended with darolutamide and docetaxel versus ADT, docetaxel, and placebo (HR, 0.79; 95% CI, 0.66-0.95; P =.01), as was the time to a first symptomatic skeletal event (HR, 0.71; 95% CI, 0.54-0.94; P =.02), and the time to initiation of subsequent antineoplastic therapy (HR, 0.39; 95% CI, 0.33 to 0.46; P <.001).

In terms of safety, grade 3 or 4 AEs were seen in 66.1% of the darolutamide arm compared with 63.5% of the control arm. The most common grade 3/4 AEs in the darolutamide arm versus the control arm, respectively was neutropenia (33.7% vs 34.2%). Serious AEs were observed in 44.8% of patients who were treated with darolutamide compared with 42.3% of those in the control arm.

The label for darolutamide warns about the risk of embryo-fetal toxicity. Further, serious AE occurring in 25% of patients treated with the agent include urinary retention, pneumonia, and hematuria. Clinically significant AEs observed with darolutamide include ischemic heart disease (4.0%), and heart failure (2.1%), according to the drug’s label.1

Currently, darolutamide has an FDA indication for the treatment of patients with non-metastatic castration-resistant prostate cancer. If the sNDA currently under review leads to an FDA approval, darolutamide will also be available for the treatment of patients with metastatic disease.


1. U.S. 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/3kyRMhZ

2. ODM-201 in addition to standard adt and docetaxel in metastatic castration sensitive prostate cancer (ARASENS). Clinicaltrials.gov. Updated March 31, 2022. Accessed May 3, 2022. https://clinicaltrials.gov/ct2/show/NCT02799602

3. Smith MR, Hussain M, Saad F, et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. Published online February 17. 2022. doi: 10.1056/NEJMoa2119115

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