Darolutamide in Combination With Androgen-Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer From the Phase III ARANOTE Trial

作者：Fred Saad, Egils Vjaters, Neal D. Shore, David Olmos, Nianzeng Xing, Andrea Juliana Gomes, Augusto César de Andrade Mota, Pamela Salman, Mindaugas Jievaltas, Albertas Ulys, M. Jakubovskis, Evgeny Kopyltsov, Weiqing Han, Liina Nevalaita, Isabella Testa, Marie‐Aude Le Berre, Iris Kuss, Kunhi Parambath Haresh, Vinod Ganju, Howard Gurney, Laurence E. Krieger, Vineet Kwatra, Sanjeev Sewak, Amanda Gwendolyn Stevanovic, Andrew Weickhardt, Alan A. Azambuja, Flavio Mavignier Cárcano, Mateus Gonçalves Costa, Felipe José Silva Melo Cruz, Juliana de Menezes, Charles Andreé Joseph de Pádua, Adriano Augusto Peclat de Paula, Carlos Eugênio Escovar, Fabio Leite Couto Fernandez, O. Gampel, Andrea Juliana Gomes, Murilo Luz, Gisele Marinho dos Santos, Augusto César de Andrade Mota, Lucas Nogueira, Daniel D’Almeida Preto, Alexandre C. Sant'Anna, Katsuki Arima Tiscoski, Jonathan Giddens, G. Kenneth Jansz, Julian Kim, Paul Quellette, Fred Saad, George Vrabec, Alejandro Acevedo Gaete, Christian Caglevic Medina, Javier Domínguez Cruzat, Marcelo Garrido Salvo, Pedro Arroyo, Anibal Salazar Huerta, Pamela Salman Boghikian, Yasna Daniela Valenzuela Velasquez, Ariel Osvaldo Zwenger, Cheng Fu, Hongqian Guo, Weiqing Han, Haowen Jiang, Junhui Jiang, Shusuan Jiang, Lie Li, Tongzu Liu, Zhenhua Liu, Lulin Ma, Jun Qi, Mingxing Qiu, Guowei Shi, Ye Tian, Ben Wan, Chun-xi Wang, Dongwen Wang, Shaogang Wang, Xiaolin Wang, Shaozhong Wei, Jitao Wu, Jun Xiao, Keji Xie, Liping Xie, Nianzeng Xing, Boxin Xue, Zejun Yan, Yongsheng Yang, Zhixian Yu, Dahong Zhang, Song Zheng, Fangjian Zhou, Suresh G. Advani, Pawan Agarwal, Niraj Bhatt, Dubashi Biswajit, Ghanashyam Biswas, Shailesh Bondarde, Chandan J. Das, SarojKumar Das Majumdar, Sujoy Gupta, Kunhi Parambath Haresh, Francis V. James, Pamela Jeyaraj, Amit Joshi, Suman Kalyan, Bhalchandra Kashyapi, Ashish Kaushal, Raghunath Krishnappa, Ravimohan S. Mavuduru, Rajanish Nagarkar, Harsha Panchal, Gourav Parkash, Ashwin Philips, Ginil Kumar Pooleri, Vikram Prabha, Krishna Kumar Rathnam, Naveen Ravel, Sudhir Rawal, Boya Rakesh Reddy, Manasi Shah, Praveena Voonna, Andrejs Aleksandrovs, M. Jakubovskis, Alvis Laukmanis, V. Lietuvietis, Mareks Vejins, Egils Vjaters, Mindaugas Jievaltas, Albertas Ulys, Raimundas Venckus, A. Želvys, Kevin Bax, Peter Gilling, Michael Holmes, Alvin Tan, Carlos Manuel Morante Deza, Alberto Juan Pazos Franco, Jorge Fernando Salas Sanchez, Alejandro Figueroa Torrejon, Timur Andabekov, Vagif Atduev, Yana Chapko, Natalya Fadeeva, Alexander Filippov, Rustem Gafanov, Oleg Gladkov, Борис Каспаров, Denis Kholtobin, Evgeny Kopyltsov, А. П. Лыков, Marina Nechaeva, Alexey Plekhanov, Sufia Safina, Andrey Semenov, Mikhail Shkolnik, Pavel Skopin, R. V. Smirnov, Ekaterina Solovyeva, А. В. Султанбаев, M. O. Zavyalov, Alexandr V. Zyryanov, Khabane Chabane, Corlia Coetzee, Conrad Jacobs, Thamsanqa Madlala, Jorn Malan, Sophie Mathijs, Carlos Llorente Abarca, D.E. Castellano Gauna, J.L. Álvarez-Ossorio Fernández, Enrique Gallardo Díaz, Pablo Borrega García, Bernardo Herrera‐Imbroda, R.A. Medina López, Josep María Gaya Sopena, Hsiao‐Jen Chung, Shu‐Pin Huang, Yuh-Shya Tsai, Pai-Fu Wang, Shian‐Shiang Wang, Igor Bondarenko, Yurii Golovko, Petro Ivashchenko, V. M. Paramonov · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco-24-01798 · 被引用次数：162 · 研究领域：Prostate Cancer Treatment and Research、Prostate Cancer Diagnosis and Treatment、Cancer, Lipids, and Metabolism

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 tw...