On August 5, 2022, the Food and Drug Administration approved darolutamide (Nubeqa, Bayer HealthCare Pharmaceuticals Inc.) tablets in combination with docetaxel for adult patients with metastatic hormone-sensitive prostate cancer (mHSPC).

Efficacy was based on ARASENS (NCT02799602), a randomized, multicenter, double-blind, placebo-controlled clinical trial in 1306 patients with mHSPC. Patients were randomized to receive either darolutamide 600 mg orally twice daily plus docetaxel 75 mg/m2 intravenously administered every 3 weeks for up to 6 cycles or docetaxel plus placebo. All patients received a gonadotropin-releasing hormone analog concurrently or had a bilateral orchiectomy.

The primary efficacy measure was overall survival (OS). Time-to-pain progression was an additional efficacy measure. Median OS was not reached (NR) (95% CI: NR, NR) in the darolutamide plus docetaxel arm and 48.9 months (95% CI: 44.4, NR) in docetaxel plus placebo arm (HR 0.68; 95% CI: 0.57, 0.80; p<0.0001). Treatment with darolutamide and docetaxel resulted in a statistically significant delay in time-to-pain progression (HR 0.79; 95% CI: 0.66, 0.95; 1-sided p=0.006).

The median age of patients was 67 years (41 to 89) and 17% were 75 years or older. Selected demographics were reported as follows: 52% White, 36% Asian, 4% Black or African American, 7% Hispanic/Latino. Three percent of patients had M1a disease (spread to distant lymph nodes), 83% had M1b (spread to bones), and 14% had M1c (spread to organs).

The most common adverse reactions experienced by patients (incidence ≥10% with a ≥2% increase over placebo with docetaxel) were constipation, decreased appetite, rash, hemorrhage, increased weight, and hypertension. The most common laboratory test abnormalities (≥30%) were anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased AST, increased ALT, and hypocalcemia.

The recommended darolutamide dose for mHSPC is 600 mg (two 300 mg tablets) taken orally, twice daily, with food until unacceptable toxicity or disease progression. Docetaxel, 75 mg/m2 intravenously is administered every 3 weeks for up to 6 cycles. The first dose of docetaxel should be administered within 6 weeks after the start of darolutamide treatment.

View full prescribing information for Nubeqa.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with Health Canada, the Singapore Health Sciences Authority, Switzerland’s Swissmedic, the United Kingdom’s Medicines and Healthcare products Regulatory Authority, and Australia’s Therapeutic Goods Administration. The application reviews may be ongoing at the other regulatory agencies.

This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application approximately one month ahead of the FDA goal date.

This application was granted priority review. A description of FDA expedited programs can be found in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email [email protected].

Follow the Oncology Center of Excellence on Twitter @FDAOncology.