In ARASENS, darolutamide (DARO) + ADT + docetaxel significantly improved overall survival (OS) vs ADT + docetaxel in patients with mHSPC, and incidences of treatment-emergent adverse events (TEAEs) were similar in both groups. The phase 3 global ARANOTE trial (NCT04736199) compared DARO + ADT vs ADT in pts with mHSPC. Primary results are reported.
Methods
Eligible pts had mHSPC by conventional imaging, an ECOG performance status of 0–2, and started ADT ≤12 weeks. Pts were randomized 2:1 to DARO 600 mg twice daily or placebo (PBO), each with ADT. The primary endpoint was radiological progression-free survival (rPFS). Secondary endpoints included OS, time to initiation of subsequent anticancer therapy, time to castration-resistant prostate cancer (CRPC), time to prostate-specific antigen (PSA) progression, time to pain progression, and safety.
Results
A total of 669 patients were randomized (DARO, N=446; PBO, N=223); median age was 70 y; 31% were Asian, 9.7% were Black, median PSA at baseline was 21.3 ng/mL, and 71% had high-volume mHSPC. At the primary data cutoff (June 7, 2024), DARO + ADT significantly improved rPFS vs PBO + ADT (HR 0.54; 95% CI 0.41–0.71; P<0.0001) with consistent benefits observed across prespecified subgroups, including patients with high- and low-volume mHSPC. DARO was associated with a positive trend for OS (HR 0.81; 95% CI,0.59–1.12) and clinical benefits across all secondary efficacy endpoints, including time to CRPC (HR 0.40; 95% CI, 0.32–0.51), time to PSA progression (HR 0.31; 95% CI 0.23–0.41), time to subsequent therapy (HR 0.40; 95% CI, 0.29–0.56), and time to pain progression (HR 0.72; 95% CI, 0.54–0.96). Incidences of TEAEs were low and similar between groups, and treatment discontinuations due to TEAEs were lower in patients receiving DARO vs PBO (6.1% vs 9.0%).
Conclusions
ARANOTE confirms the strong efficacy and favorable tolerability of DARO in mHSPC. ARASENS and ARANOTE demonstrate the benefit of DARO with and without chemotherapy, providing the option to tailor treatment, and allowing patients to live longer without progression and with minimal treatment burden.
Clinical trial identification
NCT04736199.