Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer

作者：Kim N. Chi, Dana E. Rathkopf, Matthew Raymond Smith, Eleni Efstathiou, Gerhardt Attard, David Olmos, Ji Youl Lee, Eric Jay Small, Andrea Juliana Gomes, Guilhem Roubaud, Marniza Bte Saad, Bogdan A. Żurawski, V.S. Sakalo, Gary E. Mason, Peter St. John Francis, George C. Wang, Daphne Chen Nee Wu, Brooke Diorio, Angela Lopez‐Gitlitz, Shahneen Kaur Sandhu, on behalf of the MAGNITUDE Principal Investigators, María Alejandra Álvarez, Gabriela Gatica, Martín Greco, Ernesto Pablo Korbenfeld, Esteban Metrebián, Jorge Salinas, Alejandro Salvatierra, Marcelo Daniel Tatangelo, Tom Ferguson, Howard Gurney, Elizabeth Jane Hovey, Anthony Michael Joshua, Matos Marco, Gavin M. Marx, Michelle A. Morris, Siobhan Su Wan Ng, David William Pook, Shahneen Kaur Sandhu, Ali Reza Tafreshi, Thean Hsiang Tan, Tsvetanka Tosheva, Livia Andrade, Felipe Melo Cruz, Luiza Dib Batista Bugiato Faria, J. M. L. Figueiredo, Fabio Andre Franke, Andrea Juliana Gomes, Ariel Galapo Kann, Celio Kussumoto, Suelen Patrícia dos Santos Martins, André Márcio Murad, Hélio Pinczowski, Giovani Thomaz Pioner, Luís Ferreira Pires, Daniel D’Almeida Preto, Gisele Marinho dos Santos, Eduardo Silva, Jamile Silva, Luciano de Souza Viana, Karina Vianna, Adriano Augusto Peclat de Paula, Zhiwen Chen, Kim Chi, Urban Emmenegger, Neil Eric Fleshner, Sunil Parimi, Fred Saad, Francisco Vera-Badillo, Hongqian Guo, Hong Mei Luo, Lulin Ma, Mingxing Qui, Wei Xue, Guo Yonglian, Lei Li, Jinxian Pu, Song Zheng, Qing Zou, Miloš Broďák, Milan Hora, Vladimír Šámal, Vladimír Študent, J Vaňásek, Emmanuelle Bompas, Philippe Barthélémy, Delphine Borchiellini, Aude Fléchon, Hakim Mahammedi, Guilhem Roubaud, Antoine Thiery-Vuillemin, Diégo Tosi, Dominique Spaëth, Carole Hélissey, Martin Boegemann, Susan Feyerabend, Eva Hellmis, Martin Schostak, Gerhardt Attard, Anna Lydon, Ian Sayers, Omi Parikh, Duncan A. Wheatley, Peter Arkosy, József Erfán, Lajos Géczi, Péter Nyírády, Judit Oláh, István Papos, Béla Pikó, Raanan Berger, Avivit Peer, Umberto Basso, Sergio Bracarda, Orazio Caffo, Francesco Carrozza, Gianluca Del Conte, Luca Galli, Donatello Gasparro, Sandro Pignata, Riccardo Ricotta, Daniele Santini, Giampaolo Tortora, Seok‐Soo Byun, SeolHo Choo, Byung Ha Chung, Jaeyoung Joung, Wonho Jung, Taek Won Kang, Cheol Hun Kwak, TaeGyun Kwon, Hyo Jin Lee, Ji Youl Lee, SeongIl Seo, Young Deuk Choi, H.K. Ha, ChoungSoo Kim, Flora Li Tze Chong, Chun Sen Lim, Vijayan Manogran, Hwoei Fen Soo Hoo, Guan Chou Teh, Marniza Bte Saad, David Calvo Dominguez, Abraham Cardenas, J. Ángel García Sáenz, Andre Bergman, Helgi H. Helgason, Cornelis B. Hunting, Rik Somford, Tomasz Byrski, Tomasz Adam Drewa, Dorota Filarska, Jolanta LuniewskaBury, Adam Marcheluk, Konrad Tałasiewicz, Krzysztof Tupikowski, Renata Zaucha, Bogdan A. Żurawski, Pedro P. Madeira, André Mansinho, Nuno Vau, Anna V. Alyasova, Victoria Chistyakova, Denis Khvorostenko, Dmitry Kirtbaya, Г. П. Колесников, Evgeny Kopyltsov, Igor Lifirenko, Alexander P. Lykov, Konstantin Penkov, Andrey Semenov, Mikhail Shkolnik, Павел Игоревич Скопин, R. V. Smirnov, Evgeny A. Usynin, Sergey Varlamov, Vladimir Ivanovich Vladimirov, Teresa Alonso, Sara Martínez Breijo, Elena Castro, Enrique Gallardo, Jose Gutierrez Banos, Álvaro Juárez, Rebeca Lozano, Pablo Maroto, Javier Puente, Alejo Rodríguez‐Vida, Regina Gironés, Begoña Mellado, Enrique Castellanos, Chunde Li, Chao‐Hsiang Chang, Hsiao‐Jen Chung, Kuan‐Hua Huang, Yen‐Chuan Ou, Yu‐Chieh Tsai, Shian‐Shiang Wang, Wen‐Jeng Wu, See Tong Pang, Çağatay Arslan, Devrim Çabuk, Hasan Şenol Çoşkun, Mahmut Gümüş, Mustafa Özgüroğlu, Berna Çakmak Öksüzoğlu, Berksoy Şahin, Deniz Güncel Tural, Bülent Yalçın, İrfan Çiçin, Igor Bondarenko, Yaroslav Gotsuliak, Yevhen Hotko, Геннадій Хареба, Oleksandr Lychkovskyy, Iryna Lytvyn, Taron Nalbandyan, V. M. Paramonov, Valerii Sakalo, Eduard O. Stakhovsky, Viktor P. Stus, Sunil Babu, Alan Haruo Bryce, David B. Cahn, Herta H. Chao, Franklin M. Chu, Curtis J. Dunshee, Oscar B. Goodman, Michael Grable, Jason M. Hafron, Joelle Hamilton, Ralph J. Hauke, Joseph J. Maly, David S. Morris, Gregg C. Newman, Patrick Glen Pilie, Neal D. Shore, PAUL R. SIEBER, Matthew R. Smith, Andrew F. Trainer, Ronald F. Tutrone Jr. · 发表于：Journal of Clinical Oncology · 年份：2023 · DOI：10.1200/jco.22.01649 · 被引用次数：348 · 研究领域：Prostate Cancer Treatment and Research、PARP inhibition in cancer therapy、Prostate Cancer Diagnosis and Treatment

PURPOSE Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition. METHODS MAGNITUDE (ClinicalTrials.gov identifier: NCT03748641 ) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR−, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR− cohort. RESULTS Median rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7...