The FDA approved darolutamide (Nubeqa) for metastatic castration-sensitive prostate cancer (mCSPC) based on the ARANOTE trial, which demonstrated a 46% reduction in radiographic progression-free survival (rPFS) risk compared to placebo plus androgen deprivation therapy (ADT). This approval provides oncologists with a new androgen receptor inhibitor (ARi) option for mCSPC patients, with or without concurrent docetaxel chemotherapy.
Study Design & Population
- Design: Randomized, double-blind, placebo-controlled Phase III trial (ARANOTE, NCT02799602)
- Sample Size: 669 patients with mCSPC randomized 2:1 (darolutamide:placebo)
- Treatment Arms: Darolutamide 600mg twice daily (N=446) vs placebo (N=223), both with ADT
- Population: Adult patients with metastatic castration-sensitive prostate cancer
Key Findings
- Primary Endpoint: Median rPFS not reached with darolutamide vs 25 months with placebo (HR 0.54; 95% CI: 0.41-0.71; p<0.0001)
- Risk Reduction: 46% reduction in radiographic progression or death
- Subgroup Analysis: 40% risk reduction in high-volume disease (HR 0.60) and 70% reduction in low-volume disease (HR 0.30)
- Overall Survival: No statistically significant improvement at final analysis (HR 0.78; 95% CI: 0.58-1.05)
- Safety Profile: Serious adverse events similar between arms (24% each); discontinuation rate 6% vs 9% (placebo)
Clinical Implications
- Expands treatment options for mCSPC patients beyond current ADT plus docetaxel combinations
- Provides flexibility for use with or without docetaxel chemotherapy
- Consistent safety profile with established darolutamide experience from other indications
- No new safety signals identified compared to previous approvals
Limitations
- Overall survival benefit not demonstrated at final analysis
- Study population characteristics and disease burden distribution not fully detailed
- Long-term safety data beyond established darolutamide profile not extensively reported
- Cost-effectiveness compared to other ARi options not addressed
Source: https://www.bayer.com/en/us/news-stories/metastatic-castration-sensitive-prostate-cancer
