Darolutamide in Combination With Androgen-Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer From the Phase III ARANOTE Trial
Authors: Fred Saad, Egils Vjaters, Neal Shore, David Olmos, Nianzeng Xing, Andrea Juliana Pereira de Santana Gomes, Augusto Cesar de Andrade Mota, Pamela Salman, Mindaugas Jievaltas, Albertas Ulys, Maris Jakubovskis, Evgeny Kopyltsov, Weiqing Han, Liina Nevalaita, Isabella Testa, Marie-Aude Le Berre, Iris Kuss, Kunhi Parambath Haresh, Vinod Ganju, Howard Gurney, Laurence Krieger, Vineet Kwatra, Sanjeev Sewak, Amanda Stevanovic, Andrew Weickhardt, Alan Azambuja, Flavio Mavignier Carcano, Marcio Valerio Costa, Felipe Cruz, Juliana de Menezes, Charles Andree Joseph de Padua, Adriano Augusto de Paula, Carlos Eugenio Santiago Escovar, Fabio Leite Couto Fernandez, Otavio Gampel, Andrea Juliana P. de Santana Gomes, Murilo Luz, Gisele Marinho dos Santos, Augusto Cesar de Andrade Mota, Lucas Nogueira, Daniel D'Almeida Preto, Alexandre Sant'Anna, Katsuki Aruma Tiscoski, Jonathan Giddens, Godfrey Jansz, Julian Kim, Paul Quellette, Fred Saad, George Vrabec, Alejandro Acevedo Gaete, Christian Caglevic Medina, Javier Dominguez Cruzat, Marcelo Garrido Salvo, Pedro Octavio Pastor Arroyo, Anibal Salazar Huerta, Pamela Salman Boghikian, Yasna Daniela Valenzuela Velasquez, Ariel Zwenger, Cheng Fu, Hongqian Guo, Weiqing Han, Haowen Jiang, Junhui Jiang, Shusuan Jiang, Lei 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, Yong Yang, Zhixian Yu, Dahong Zhang, Song Zheng, Fangjian Zhou, Suresh Advani, Pawan Agarwal, Niraj Bhatt, Dubashi Biswajit, Ghanashyam Biswas, Shailesh A. Bondarde, Chandan Das, SarojKumar Das Majumdar, Sujoy Gupta, Kunhi Parambath Haresh, Francis James, Pamela Jeyaraj, Amit Joshi, Suman Kalyan, Bhalchandra Kashyapi, Ashish Kaushal, Raghunath Krishnappa, Ravimohan 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, Maris Jakubovskis, Alvis Laukmanis, Vilnis Lietuvietis, Mareks Vejins, Egils Vjaters, Mindaugas Jievaltas, Albertas Ulys, Raimundas Venckus, Arunas Zelvys, 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, Boris Kasparov, Denis Kholtobin, Evgeny Kopyltsov, Alexander Lykov, Marina Nechaeva, Alexey Plekhanov, Sufia Safina, Andrey Semenov, Mikhail Shkolnik, Pavel Skopin, Roman Smirnov, Ekaterina Solovyeva, Alexander Sultanbaev, Mikhail Zavyalov, Alexandr Zyryanov, Khabane Chabane, Corlia Coetzee, Conrad Jacobs, Thamsanqa Madlala, Jorn Malan, Sophie Mathijs, Carlos Llorente Abarca, Daniel Ernesto Castellano Gauna, Jose Luis Alvarez-Ossorio Fernandez, Enrique Gallardo Diaz, Pablo Borrega Garcia, Bernardo Herrera Imbroda, Rafael Antonio Medina Lopez, Josep Maria Gaya Sopena, Hsiao-Jen Chung, Shu-Pin Huang, Yuh-Shya Tsai, Pai-Fu Wang, Shian-Shiang Wang, Igor Bondarenko, Yurii Golovko, Petro Ivashchenko, Viktor Paramonov
Journal: Journal of Clinical Oncology (2024)

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 &lt; .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 two groups. Notably, the incidence of fatigue was lower in patients receiving darolutamide (5.6%) versus those receiving placebo (8.1%), and fewer patients receiving darolutamide (6.1%) versus placebo (9.0%) discontinued treatment because of adverse events. CONCLUSION These results confirm the efficacy and tolerability of darolutamide plus ADT in patients with mHSPC, demonstrating clinically and statistically significant improvement in rPFS and a favorable safety profile consistent with prior phase III darolutamide trials.