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

Autor:	Shore ND; Carolina Urologic Research Center, Myrtle Beach, SC, USA., Gratzke C; Department of Urology, University Hospital Freiburg, Freiburg, Germany., Feyerabend S; Studienpraxis Urologie, Nürtingen, Germany., Werbrouck P; Department of Urology, AZ Groeninge, Kortrijk, Belgium., Carles J; Vall d'Hebron Institute of Oncology, Hospital Universitari Vall d'Hebron, Barcelona, Spain., Vjaters E; Urological Center, Pauls Stradiņš Clinical University Hospital, Riga, Latvia., Tammela TLJ; Department of Urology, Tampere University Hospital and Tampere University, Tampere, Finland., Morris D; Urology Associates, PC, Nashville, TN, USA., Aragon-Ching JB; Inova Schar Cancer Institute, Fairfax, VA, USA., Concepcion RS; Urology Associates, PC, Nashville, TN, USA., Emmenegger U; Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.; Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada., Fleshner N; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada., Grabbert M; Department of Urology, University Hospital Freiburg, Freiburg, Germany., Lietuvietis V; Urology Clinic, Department of Surgery, Riga East Clinical University Hospital, Riga, Latvia., Mahammedi H; Medical Oncology, Jean Perrin Center, Clermont-Ferrand, France., Cruz FM; Núcleo de Ensino e Pesquisa da Rede São Camilo, São Paulo, Brazil., Paula A; Oncologic Surgery, Hospital Araújo Jorge, Goiânia, Brazil., Pieczonka C; Associated Medical Professionals, Syracuse, NY, USA., Rannikko A; Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland., Richardet M; Oncologic Institute of Córdoba, Sanatorio Aconcagua, Córdoba, Argentina., Silveira G; Centro Oncológico do Triângulo, Uberlândia, Brazil., Kuss I; Bayer AG, Berlin, Germany., Le Berre MA; Bayer HealthCare SAS, Loos, France., Verholen F; Bayer Consumer Care AG, Basel, Switzerland., Sarapohja T; Orion Pharma, Espoo, Finland., Smith MR; Massachusetts General Hospital Cancer Center, Boston, MA, USA., Fizazi K; Institut Gustave Roussy, University of Paris-Saclay, Villejuif, France.
Jazyk:	angličtina
Zdroj:	The oncologist [Oncologist] 2024 Jul 05; Vol. 29 (7), pp. 581-588.
DOI:	10.1093/oncolo/oyae019
Abstrakt:	Background: 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 and Methods: 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. Results: 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. Conclusion: 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. Trial Number: ClinicalTrials.gov identifier NCT02200614. (© The Author(s) 2024. Published by Oxford University Press.)
Databáze:	MEDLINE
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