FDA Approval Sought for Darolutamide/Docetaxel for Metastatic Hormone-Sensitive Prostate Cancer

A supplemental new drug application (sNDA) has been submitted to the FDA for darolutamide (Nubeqa) in combination with docetaxel as a potential treatment option for patients with metastatic hormone-sensitive prostate cancer (mHSPC), according to a press release from Bayer.¹

The sNDA submission is backed by positive data from the phase 3 ARASENS trial (NCT02799602) in which darolutamide plus docetaxel achieved a 32.5% reduction in the risk of death, which was a statistically significant improvement in overall survival (OS) versus androgen deprivation therapy (ADT) and docetaxel in patients with mHSPC.

“For men with mHSPC, there remains a high need for new treatment options that can extend overall survival and delay the progression to castration resistant prostate cancer,” said Christine Roth, member of the Executive Committee of Bayer’s Pharmaceutical Division and head of the Oncology SBU at Bayer, in the press release. “Prostate cancer is a key area of focus at Bayer and the United States and European Union submissions for Nubeqa in mHSPC represent a significant milestone in our commitment to developing treatments that support men with prostate cancer throughout the different stages of the disease.”

Results from the study were recently published in the New England Journal of Medicine. The study included 1,306 patients who 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.²

The primary end point of the study is OS, and the secondary end points include 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).

Results show that 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 4 years, 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 analyzed.

In terms of the secondary study end points, 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).

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 comparator arm.

ARASENS is ongoing but has completed patient enrollment.

In additional to the US application for approval from the FDA, Bayer submitted application to the European Medicines Agency.

_REFERENCES:

_{1. Bayer submits applications in the U.S. and EU for additional indication of NUBEQA® (darolutamide). News release. Bayer. March 9, 2022. Accessed March 9, 2022. https://bit.ly/3tI2lnh}

_{2. 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}