(UroToday.com) The American Urologic Association (AUA) Southeastern Section (SES) 89th Annual Meeting held in Nashville, TN, between March 12th and 15th, 2025, was host to a prostate cancer poster session. Dr. Zachary Klaassen presented the results of the phase III ARANOTE trial evaluating the efficacy and safety of doublet darolutamide plus androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) patients.
The phase III ARASENS trial demonstrated that the addition of darolutamide (versus placebo) to ADT + docetaxel significantly improved overall survival in mHSPC patients (HR: 0.68, 95% CI: 0.57–0.80, p<0.001).1
While darolutamide has proven survival benefits for mHSPC patients in the triplet therapy setting, there has been no level 1 evidence prior to 2024 demonstrating this drug’s efficacy in the mHSPC doublet setting.
ARANOTE is a global, randomized, double-blind phase III trial that randomized 669 patients 2:1 to receive darolutamide 600 mg twice daily or placebo, with concomitant ADT. The primary endpoint was radiological progression-free survival (rPFS).
At a median follow-up of 25.3 months, darolutamide plus ADT significantly improved rPFS by 46% versus placebo plus ADT (median: not reached versus 25 months; HR: 0.54, 95% CI: 0.41–0.71, p<0.001), with consistent benefits observed in both high- and low-volume mHSPC patients. At 24 months, 70% of patients in the intervention arm remained free of radiographic progression, compared to 52% in the control arm.
Darolutamide showed a consistent benefit across all secondary endpoints. Overall survival (OS) results were suggestive of benefit with darolutamide versus placebo (24 months OS: 80% versus 75.5%; HR: 0.81, 95% CI: 0.59–1.12). The benefit was observed despite a greater proportion of patients in the placebo group (42.5%) than in the darolutamide group (32.5%) receiving subsequent life-prolonging anticancer therapy, primarily docetaxel.
The time to castration-resistance (HR: 0.40; 95% CI: 0.32–0.51) and time to PSA progression (HR: 0.31; 95% CI: 0.23–0.41) were longer with darolutamide versus placebo, and a higher proportion of patients receiving darolutamide achieved a serum PSA level <0.2 ng/mL at any time during the treatment period (63%) versus those receiving placebo (18.5%). The time to initiation of subsequent systemic anticancer therapy (HR: 0.40; 95% CI: 0.29–0.56) and time to pain progression were also delayed in the darolutamide group (HR: 0.72; 95% CI: 0.54–0.96).
The adverse event profile for darolutamide + ADT was favorable, with the incidence of any treatment-emergent adverse events similar across the treatment arms (90–91%). Grade ≥3 adverse events were observed in ~35% of patients in both arms. Notably, the incidence of fatigue was lower in darolutamide-treated patients (5.6% versus 8%), and fewer patients receiving darolutamide (6% versus 9%) discontinued treatment due to adverse events.2
Dr. Klaassen concluded his presentation of the ARANOTE trial as follows:
- Darolutamide + ADT significantly improved radiographic progression-free survival in mHSPC patients
- Darolutamide showed a benefit across all secondary endpoints with a favorable safety profile
- Darolutamide + ADT without docetaxel should become an additional standard of care for mHSPC patients
Presented by: Zachary Klaassen, MD, MSc, Associate Professor, Department of Urology, Wellstar MCG Health, Augusta, GA
Written by: Rashid K. Sayyid, MD, MSc – Robotic Urologic Oncology Fellow at The University of Southern California, @rksayyid on Twitter during the American Urologic Association (AUA) Southeastern Section (SES) 89th Annual Meeting in Nashville, TN, March 12–15th, 2025
References:- Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022; 386(12):1132-42.
- Saad F, Vjaters E, Shore N, et al. Darolutamide in Combination With Androgen-Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer From the Phase III ARANOTE Trial. J Clin Oncol. 2024; 42(36): 4271-81.