Extended Safety and Tolerability of Darolutamide for Nonmetastatic Castration-Resistant Prostate Cancer and Adverse Event Time Course in ARAMIS.

Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) are usually asymptomatic and seek treatments that improve survival but have a low risk of adverse events. Darolutamide, a structurally distinct androgen receptor inhibitor (ARi), significantly reduced the risk of metastasis and death versus placebo in ARAMIS.

We assessed the extended safety and tolerability of darolutamide and the time-course profile of treatment-emergent adverse events (TEAEs) related to ARis and androgen-suppressive treatment.

Patients with nmCRPC were randomized 2:1 to darolutamide (n = 955) or placebo (n = 554). After trial unblinding, patients could receive open-label darolutamide. Tolerability and TEAEs were assessed every 16 weeks. Time interval-specific new and cumulative event rates were determined during the first 24 months of the double-blind period.

Darolutamide remained well tolerated during the double-blind and open-label periods, with 98.8% of patients receiving the full planned dose. The incidence of TEAEs of interest in the darolutamide group was low and ≤2% different from that in the placebo group, except for fatigue. When incidences were adjusted for exposure time, there were minimal differences between the darolutamide double-blind and double-blind plus open-label periods. The rate of initial onset and cumulative incidence of grade 3/4 TEAEs and serious TEAEs were similar for darolutamide and placebo groups over 24 months.

Extended treatment with darolutamide was well tolerated and no new safety signals were observed. Most ARi-associated and androgen-suppressive treatment-related TEAEs occurred at low incidences with darolutamide, were similar to placebo, and showed minimal increase over time with continued treatment.

ClinicalTrials.gov identifier NCT02200614.

The oncologist. 2024 Feb 23 [Epub ahead of print]

Neal D Shore, Christian Gratzke, Susan Feyerabend, Patrick Werbrouck, Joan Carles, Egils Vjaters, Teuvo L J Tammela, David Morris, Jeanny B Aragon-Ching, Raoul S Concepcion, Urban Emmenegger, Neil Fleshner, Markus Grabbert, Vilnis Lietuvietis, Hakim Mahammedi, Felipe M Cruz, Adriano Paula, Christopher Pieczonka, Antti Rannikko, Martin Richardet, Glauco Silveira, Iris Kuss, Marie-Aude Le Berre, Frank Verholen, Toni Sarapohja, Matthew R Smith, Karim Fizazi

Carolina Urologic Research Center, Myrtle Beach, SC, USA., Department of Urology, University Hospital Freiburg, Freiburg, Germany., Studienpraxis Urologie, Nürtingen, Germany., Department of Urology, AZ Groeninge, Kortrijk, Belgium., Vall d'Hebron Institute of Oncology, Hospital Universitari Vall d'Hebron, Barcelona, Spain., Urological Center, Pauls Stradiņš Clinical University Hospital, Riga, Latvia., Department of Urology, Tampere University Hospital and Tampere University, Tampere, Finland., Urology Associates, PC, Nashville, TN, USA., Inova Schar Cancer Institute, Fairfax, VA, USA., Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada., Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Urology Clinic, Department of Surgery, Riga East Clinical University Hospital, Riga, Latvia., Medical Oncology, Jean Perrin Center, Clermont-Ferrand, France., Núcleo de Ensino e Pesquisa da Rede São Camilo, São Paulo, Brazil., Oncologic Surgery, Hospital Araújo Jorge, Goiânia, Brazil., Associated Medical Professionals, Syracuse, NY, USA., Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland., Oncologic Institute of Córdoba, Sanatorio Aconcagua, Córdoba, Argentina., Centro Oncológico do Triângulo, Uberlândia, Brazil., Bayer AG, Berlin, Germany., Bayer HealthCare SAS, Loos, France., Bayer Consumer Care AG, Basel, Switzerland., Orion Pharma, Espoo, Finland., Massachusetts General Hospital Cancer Center, Boston, MA, USA., Institut Gustave Roussy, University of Paris-Saclay, Villejuif, France.