Matthew R Smith1, Maha Hussain1, Fred Saad1, Karim Fizazi1, Cora N Sternberg1, E David Crawford1, Evgeny Kopyltsov1, Chandler H Park1, Boris Alekseev1, Álvaro Montesa-Pino1, Dingwei Ye1, Francis Parnis1, Felipe Cruz1, Teuvo L J Tammela1, Hiroyoshi Suzuki1, Tapio Utriainen1, Cheng Fu1, Motohide Uemura1, María J Méndez-Vidal1, Benjamin L Maughan1, Heikki Joensuu1, Silke Thiele1, Rui Li1, Iris Kuss1, Bertrand Tombal1. 1. From the Massachusetts General Hospital Cancer Center and Harvard Medical School - both in Boston (M.R.S.); the Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago (M.H.); the University of Montreal Hospital Center, Montreal (F.S.); Institut Gustave Roussy, University of Paris-Saclay, Villejuif, France (K.F.); the Englander Institute for Precision Medicine, Weill Cornell Medicine, Meyer Cancer Center, New York-Presbyterian Hospital, New York (C.N.S.); the University of California San Diego School of Medicine, La Jolla (E.D.C.); the Clinical Oncologic Dispensary of Omsk Region, Omsk (E.K.), and P. Hertsen Moscow Oncology Research Institute, Moscow (B.A.) - both in Russia; Norton Cancer Institute, Louisville, KY (C.H.P.); La Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen Victoria, Instituto de Investigación Biomédica de Málaga, Malaga (A.M.-P.), and Maimonides Institute for Biomedical Research of Córdoba, Reina Sofía University Hospital, Cordoba (M.J.M.-V.) - both in Spain; Fudan University Shanghai Cancer Center, Shanghai (D.Y.), and Liaoning Cancer Hospital and Institute, Shenyang (C.F.) - both in China; Ashford Cancer Centre Research, Kurralta Park, SA, Australia (F.P.); Núcleo de Pesquisa e Ensino da Rede São Camilo, São Paulo (F.C.); Tampere University Hospital and Tampere University, Tampere (T.L.J.T.), Helsinki University Central Hospital, Comprehensive Cancer Center, Helsinki (T.U.), and Orion Pharma, Espoo (H.J.) - all in Finland; Toho University Sakura Medical Center, Chiba (H.S.), and Osaka University Hospital, Osaka (M.U.) - both in Japan; the Huntsman Cancer Institute, Salt Lake City (B.L.M.); Bayer, Berlin (S.T., I.K.); Bayer HealthCare, Whippany, NJ (R.L.); and the Division of Urology, Institut de Recherche Clinique, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Brussels (B.T.).
Abstract
BACKGROUND: Darolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration-resistant prostate cancer. Whether a combination of darolutamide, androgen-deprivation therapy, and docetaxel would increase survival among patients with metastatic, hormone-sensitive prostate cancer is unknown. METHODS: In this international, phase 3 trial, we randomly assigned patients with metastatic, hormone-sensitive prostate cancer in a 1:1 ratio to receive darolutamide (at a dose of 600 mg [two 300-mg tablets] twice daily) or matching placebo, both in combination with androgen-deprivation therapy and docetaxel. The primary end point was overall survival. RESULTS: The primary analysis involved 1306 patients (651 in the darolutamide group and 655 in the placebo group); 86.1% of the patients had disease that was metastatic at the time of the initial diagnosis. At the data cutoff date for the primary analysis (October 25, 2021), the risk of death was significantly lower, by 32.5%, in the darolutamide group than in the placebo group (hazard ratio 0.68; 95% confidence interval, 0.57 to 0.80; P<0.001). Darolutamide was also associated with consistent benefits with respect to the secondary end points and prespecified subgroups. Adverse events were similar in the two groups, and the incidences of the most common adverse events (occurring in ≥10% of the patients) were highest during the overlapping docetaxel treatment period in both groups. The frequency of grade 3 or 4 adverse events was 66.1% in the darolutamide group and 63.5% in the placebo group; neutropenia was the most common grade 3 or 4 adverse event (in 33.7% and 34.2%, respectively). CONCLUSIONS: In this trial involving patients with metastatic, hormone-sensitive prostate cancer, overall survival was significantly longer with the combination of darolutamide, androgen-deprivation therapy, and docetaxel than with placebo plus androgen-deprivation therapy and docetaxel, and the addition of darolutamide led to improvement in key secondary end points. The frequency of adverse events was similar in the two groups. (Funded by Bayer and Orion Pharma; ARASENS ClinicalTrials.gov number, NCT02799602.).
BACKGROUND: Darolutamide is a potent androgen-receptor inhibitor that has been associated with increased overall survival among patients with nonmetastatic, castration-resistant prostate cancer. Whether a combination of darolutamide, androgen-deprivation therapy, and docetaxel would increase survival among patients with metastatic, hormone-sensitive prostate cancer is unknown. METHODS: In this international, phase 3 trial, we randomly assigned patients with metastatic, hormone-sensitive prostate cancer in a 1:1 ratio to receive darolutamide (at a dose of 600 mg [two 300-mg tablets] twice daily) or matching placebo, both in combination with androgen-deprivation therapy and docetaxel. The primary end point was overall survival. RESULTS: The primary analysis involved 1306 patients (651 in the darolutamide group and 655 in the placebo group); 86.1% of the patients had disease that was metastatic at the time of the initial diagnosis. At the data cutoff date for the primary analysis (October 25, 2021), the risk of death was significantly lower, by 32.5%, in the darolutamide group than in the placebo group (hazard ratio 0.68; 95% confidence interval, 0.57 to 0.80; P<0.001). Darolutamide was also associated with consistent benefits with respect to the secondary end points and prespecified subgroups. Adverse events were similar in the two groups, and the incidences of the most common adverse events (occurring in ≥10% of the patients) were highest during the overlapping docetaxel treatment period in both groups. The frequency of grade 3 or 4 adverse events was 66.1% in the darolutamide group and 63.5% in the placebo group; neutropenia was the most common grade 3 or 4 adverse event (in 33.7% and 34.2%, respectively). CONCLUSIONS: In this trial involving patients with metastatic, hormone-sensitive prostate cancer, overall survival was significantly longer with the combination of darolutamide, androgen-deprivation therapy, and docetaxel than with placebo plus androgen-deprivation therapy and docetaxel, and the addition of darolutamide led to improvement in key secondary end points. The frequency of adverse events was similar in the two groups. (Funded by Bayer and Orion Pharma; ARASENS ClinicalTrials.gov number, NCT02799602.).
Authors: Peter C Black; Nazanin Fallah-Rad; Andrew Loblaw; Elie Kassouf; Mira Keyes; Naveen S Basappa; Anand Swaminath Journal: Can Urol Assoc J Date: 2022-09 Impact factor: 2.052
Authors: Anil Kapoor; Tamim Niazi; Krista Noonan; Ricardo A Rendon; Nimira Alimohamed; Wassim Kassouf; Alejandro Berlin; William Chu; Christian Kollmannsberger; Alan I So Journal: Can Urol Assoc J Date: 2022-04 Impact factor: 2.052
Authors: Marc Casper Meineche Andersen; Hein Vincent Stroomberg; Klaus Brasso; John Thomas Helgstrand; Andreas Røder Journal: Diagnostics (Basel) Date: 2022-05-19