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

2024; Lippincott Williams & Wilkins; Linguagem: Inglês

10.1200/jco-24-01798

1527-7755

Fred Saad, Egils Vjaters, Neal D. Shore, David Olmos, Nianzeng Xing, Andrea Juliana Pereira de Santana 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, Mario Alberto Dantas L. da 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 Pereira de Santana 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, Qiu Ming-xing, 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, Biswajit Dubashi, 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, Rajnish Nagarkar, Harsha Panchal, Gourav Parkash, Ashwin Philips, Ginil Kumar Pooleri, Vikram Prabha, Krishna Kumar Rathnam, Naveen Ravel, Sudhir Rawal, Balaji Reddy, Manasi Shah, Praveena Voonna, Andrejs Aleksandrovs, M. Jakubovskis, Alvis Laukmanis, Vilnis 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, Antonio Franco, Julian 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, М. I. Shkolnik, Pavel Skopin, R. V. Smirnov, Ekaterina Solovyeva, А. В. Султанбаев, M. O. Zavyalov, Alexandr V. Zyryanov, Kahina Chabane, Corlia Coetzee, Conrad Jacobs, Thamsanqa Madlala, Jacques Malan, Sophie Mathijs, C. 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 M. Sopena, Hsiao‐Jen Chung, Shu‐Pin Huang, Yu-Chin Tsai, Pai-Fu Wang, Shian‐Shiang Wang, Igor Bondarenko, Yurii Golovko, Petro Ivashchenko, V. M. Paramonov,

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 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.