Darolutamide in Combination With Androgen-Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer From the Phase III ARANOTE Trial
Mené sur 699 patients atteints d'un cancer de la prostate hormonosensible et de stade métastatique, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout de darolutamide à une thérapie anti-androgénique
Résumé en anglais
Purpose: For patients with metastatic hormone-sensitive prostate cancer (mHSPC), delaying progression to castration-resistant disease is important not only for overall survival (OS) but also for patients' quality of life . Darolutamide plus androgen-deprivation therapy (ADT) with docetaxel improved OS versus ADT and docetaxel in patients with mHSPC. The ARANOTE trial evaluated darolutamide and ADT without chemotherapy in patients with mHSPC.
Methods: In this global phase 3 trial, patients were randomized 2:1 to receive darolutamide 600 mg twice daily or placebo, with concomitant ADT. The primary endpoint was radiological progression-free survival (rPFS).
Results: From March 2021 to August 2022, 669 patients were randomized (darolutamide n=446; placebo n=223). At the primary cutoff date (June 7, 2024), darolutamide plus ADT significantly improved rPFS by 46% versus placebo plus ADT (hazard ratio [HR] 0.54; 95% confidence interval [CI], 0.41–0.71; P<0.0001), with consistent benefits across subgroups, including high- and low-volume disease. OS results were suggestive of benefit with darolutamide versus placebo (HR 0.81; 95% CI, 0.59–1.12) and clinical benefits were seen across all other secondary endpoints, including delayed time to castration-resistant prostate cancer (HR 0.40; 95% CI, 0.32–0.51) and time to pain progression (HR 0.72; 95% CI, 0.54–0.96). Adverse events were similar in the two groups. Notably, the incidence of fatigue was lower in patients receiving darolutamide (5.6%) versus those receiving placebo (8.1%), and fewer patients receiving darolutamide (6.1%) versus placebo (9.0%) discontinued treatment due to adverse events.
Conclusion: These results confirm the efficacy and tolerability of darolutamide plus ADT in patients with mHSPC, demonstrating clinically and statistically significant improvement in rPFS and a favorable safety profile consistent with prior phase 3 darolutamide trials.
