Author(s): Fred Saad, MD1; Egils Vjaters, MD2; Neal Shore, MD, FACS3; David Olmos, MD, PhD4; Nianzeng Xing, MD5; Andrea Juliana Pereira de Santana Gomes, MD6; Augusto Cesar de Andrade Mota, MD, PhD7; Pamela Salman, MD, PhD8; Mindaugas Jievaltas, MD, PhD9; Albertas Ulys, MD, PhD10; Maris Jakubovskis, MD11; Evgeny Kopyltsov, MD, PhD12; Weiqing Han, MD, PhD13; Liina Nevalaita, PhD14; Isabella Testa, MD15; Marie-Aude Le Berre, MSc16; Iris Kuss, MD17; Kunhi Parambath Haresh, MD18
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 III trial, patients were randomly assigned 2:1 to receive darolutamide 600 mg twice daily or placebo, with concomitant ADT. The primary end point was radiological progression-free survival (rPFS).
RESULTS
From March 2021 to August 2022, 669 patients were randomly assigned (darolutamide n = 446; placebo n = 223). At the primary cutoff date (June 7, 2024), darolutamide plus ADT significantly improved rPFS, reducing the risk of radiological progression or death by 46% versus placebo plus ADT (hazard ratio [HR], 0.54 [95% CI, 0.41 to 0.71]; P < .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 to 1.12]), and clinical benefits were seen across all other secondary end points, including delayed time to metastatic castration-resistant prostate cancer (HR, 0.40 [95% CI, 0.32 to 0.51]) and time to pain progression (HR, 0.72 [95% CI, 0.54 to 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 because of 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 III darolutamide trials.
Author Affiliations
1 Department of Surgery/Urology, Centre Hospitalier de l’Université de Montréal, University of Montreal, Montreal, QC, Canada; 2 P. Stradinš Clinical University Hospital, Riga, Latvia; 3 Carolina Urologic Research Center and AUC Urology Specialists, Myrtle Beach, SC; 4 Department of Medical Oncology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (Imas 12), Madrid, Spain; 5 Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; 6 Liga Norte Riograndense Contra O Cancer, Natal, Brazil; 7 Medical Oncology, Instituto ETICA—Clinica AMO/DASA, Salvador, Brazil; 8 Oncovida Research, Santiago, Chile; 9 Lithuanian University of Health Sciences, Medical Academy, Kaunas, Lithuania; 10 National Cancer Institute, Vilnius University, Vilnius, Lithuania; 11 Clinic of Urology and Oncological Urology, Riga East University Hospital, Riga, Latvia; 12 Clinical Oncological Dispensary of Omsk Region, Omsk, Russian Federation; 13 Department of Urology, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Hunan Cancer Center, Changsha, China; 14 Orion Corporation, Orion Pharma, Espoo, Finland; 15 Bayer S.p.A, Milan, Italy; 16 Bayer Healthcare SAS, Lille, France; 17 Bayer AG, Berlin, Germany; 18 All India Institute of Medical Sciences, New Delhi, India;
