Patients with metastatic hormone-sensitive prostate cancer (mHSPC) require long-term treatment to delay progression and improve survival, while minimizing adverse events or negative impact on symptoms (e. g. pain) and health-related quality of life (HRQoL). In ARASENS (NCT02799602), darolutamide plus androgen deprivation therapy (ADT) and docetaxel significantly improved overall survival (primary endpoint) versus placebo plus ADT and docetaxel. We report clinically relevant endpoints and HRQoL in ARASENS.
Patients with mHSPC were randomized to darolutamide 600 mg orally twice daily or placebo, with ADT and docetaxel. Outcomes of interest were times to metastatic castration-resistant prostate cancer (mCRPC), pain progression, worsening of Brief Pain Inventory-Short Form pain interference/severity, and worsening of National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy Prostate Cancer Symptom Index 17-item questionnaire (NFPSI-17) scores.
In 1305 patients analyzed (darolutamide 651, placebo 654), darolutamide significantly delayed time to mCRPC (hazard ratio 0.36 [95 % confidence interval 0.30-0.42]) and time to pain progression (0.79 [0.66-0.95]) versus placebo. Times to worsening of pain interference/severity and NFPSI-17 scores were similar between treatment groups. Incidences of treatment-emergent adverse events (TEAEs) commonly associated with androgen receptor pathway inhibition were generally low and similar between groups (median follow-up: > 3.5 years).
Darolutamide plus ADT and docetaxel provided significant benefits in clinically relevant endpoints versus ADT and docetaxel, with similar control of pain, maintenance of HRQoL, and no cumulative TEAEs over long-term treatment. These data reinforce darolutamide triplet therapy as a standard-of-care treatment option in patients with mHSPC.
European journal of cancer (Oxford, England : 1990). 2026 Jun 12 [Epub ahead of print]
Karim Fizazi, Matthew R Smith, Maha Hussain, Fred Saad, Cora N Sternberg, E David Crawford, Jeanny B Aragon-Ching, Martin Schostak, Ronald Tutrone, Alicia K Morgans, Daniel Sentana-Lledo, Heikki Joensuu, Ateesha F Mohamed, Natasha Littleton, Shankar Srinivasan, Yvonne Buttkewitz, Rui Li, Iris Kuss, Bertrand Tombal
Department of Cancer Medicine, Centre Oscar Lambret, Institute Gustave Roussy, University of Paris-Saclay, Lille, France. Electronic address: ., Genitourinary Oncology Program, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA, USA., Division of Hematology-Oncology, Department of Medicine, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Department of Urology, University of Montreal Hospital Center, Montreal, QC, Canada., Englander Institute for Precision Medicine, Weill Cornell Department of Medicine, Meyer Cancer Center, New York-Presbyterian Hospital, Hematology/Oncology, New York, NY, USA., Department of Urology, UC San Diego School of Medicine, La Jolla, CA, USA., Genitourinary Cancers, Inova Schar Cancer Institute, Fairfax, VA, USA., Department of Urology, Uro-oncology, Robotic and Focal Therapy, University Hospital Magdeburg, Magdeburg, Germany., Chesapeake Urology Associates, PA, Towson, MD, USA., Dana-Farber Cancer Institute, Boston, MA, USA., Lank Center for Genitourinary Cancer, Boston, MA, USA., Orion Corporation, Orion Pharma, Espoo, Finland., Bayer HealthCare Pharmaceuticals, Inc., Whippany, NJ, USA., Oncology, Bayer Limited, Stillorgan, Co., Dublin, Ireland., Chrestos GmbH (now Evidenze Germany GmbH), Essen, Germany., Bayer AG, Berlin, Germany., Division of Urology, Institut de Recherche Clinique, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Brussels, Belgium.