Multinational phase 3 trial of darolutamide plus androgen-deprivation therapy for metastatic hormone-sensitive prostate cancer

For patients with metastatic hormone-sensitive prostate cancer (mHSPC), delaying progression to castration-resistant disease is important not only for overall survival but also for quality of life. The multinational phase 3 ARANOTE trial evaluated the chemotherapy-free regimen of darolutamide plus androgen-deprivation therapy for mHSCP. Patients were randomized 2:1 to darolutamide 600 mg twice daily plus ADT or placebo plus ADT. Primary endpoint was radiological progression-free survival (rPFS). At the primary cutoff date, darolutamide plus ADT significantly improved rPFS versus placebo plus ADT (HR 0.54; p<0.0001), with consistent benefits across subgroups. Overall survival results were suggestive of benefit with darolumamide versus placebo (HR 0.81; 95% CI 0.59-1.12) and clinical benefits were seen across all other secondary endpoints, including delayed time castration-resistant prostate cancer (0.40; 0.32-0.51) and time to pain progression (0.72; 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 placebo (8.1%) as was discontinuation due to adverse events (6.1% versus 9.0%. The authors conclude that the study showed efficacy and tolerability of darolutamide plus ADT in patients with mHSPC.