Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer
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Published:2023-06-20
Issue:18
Volume:41
Page:3339-3351
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ISSN:0732-183X
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Container-title:Journal of Clinical Oncology
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language:en
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Short-container-title:JCO
Author:
Chi Kim N.1ORCID, Rathkopf Dana2, Smith Matthew R.3, Efstathiou Eleni4ORCID, Attard Gerhardt5ORCID, Olmos David6ORCID, Lee Ji Youl7ORCID, Small Eric J.8ORCID, Pereira de Santana Gomes Andrea J.9ORCID, Roubaud Guilhem10, Saad Marniza11, Zurawski Bogdan12, Sakalo Valerii13, Mason Gary E.14ORCID, Francis Peter15, Wang George14, Wu Daphne16, Diorio Brooke17, Lopez-Gitlitz Angela16, Sandhu Shahneen18ORCID, Alvarez Maria, Gatica Gabriela, Greco Martin, Korbenfeld Ernesto, Metrebian Esteban, Salinas Jorge, Salvatierra Alejandro, Tatangelo Marcelo, Ferguson Tom, Gurney Howard, Hovey Elizabeth, Joshua Anthony, Marco Matos, Marx Gavin, Morris Michelle, Ng Siobhan, Pook David, Sandhu Shahneen, Tafreshi Ali, Tan Thean Hsiang, Tosheva Tsvetanka, Andrade Livia, Cruz Felipe, Faria Luiza, Figueiredo Jose, Franke Fabio, Gomes Andrea Juliana, Kann Ariel, Kussumoto Celio, Martins Suelen, Murad Andre, Pinczowski Helio, Pioner Giovani, Pires Luis, Preto Daniel, Santos Gisele, Silva Eduardo, Silva Jamile, Viana Luciano, Vianna Karina, Paula Adriano, Chen Zhiwen, Chi Kim, Emmenegger Urban, Fleshner Neil, Parimi Sunil, Saad Fred, Vera-Badillo Francisco, Guo Hongqian, Luo Hong, Ma Lulin, Qui Mingxing, Xue Wei, Yonglian Guo, Li Lei, Pu Jinxian, Zheng Song, Zou Qing, Brodak Milos, Hora Milan, Samal Vladimir, Student Vladimir, Vanasek Jaroslav, Bompas Emmanuelle, Barthelemy Philippe, Borchiellini Delphine, Flechon Aude, Mahammedi Hakim, Roubaud Guilhem, Thiery-Vuillemin Antoine, Tosi Diego, Dominique Spaeth, Helissey Carole, Boegemann Martin, Feyerabend Susan, Hellmis Eva, Schostak Martin, Attard Gerhardt, Lydon Anna, Sayers Ian, Parikh Omi, Wheatley Duncan, Arkosy Peter, Erfan Jozsef, Geczi Lajos, Nyirady Peter, Olah Judit, Papos Istvan, Piko Bela, Berger Raanan, Peer Avivit, Basso Umberto, Bracarda Sergio, Caffo Orazio, Carrozza Francesco, Del Conte Gianluca, Galli Luca, Gasparro Donatello, Pignata Sandro, Ricotta Riccardo, Santini Daniele, Tortora Giampaolo, Byun Seoksoo, Choo SeolHo, Chung ByungHa, Joung Jaeyoung, Jung Wonho, Kang Taek Won, Kwak Cheol, Kwon TaeGyun, Lee Hyo Jin, Lee Ji Youl, Seo SeongIl, Choi YoungDeuk, Ha HongKoo, Kim ChoungSoo, Tze Chong Flora Li, Lim Chun Sen, Manogran Vijayan, Soo Hoo Hwoei Fen, Teh Guan Chou, Saad Marniza, Dominguez David Calvo, Cardenas Abraham, Saenz Julia, Bergman Andre, Helgason Helgi, Hunting C.B., Somford Rik, Byrski Tomasz, Drewa Tomasz, Filarska Dorota, LuniewskaBury Jolanta, Marcheluk Adam, Talasiewicz Konrad, Tupikowski Krzysztof, Zaucha Renata, Zurawski Bogdan, Madeira Pedro, Mansinho Andre, Vau Nuno, Alyasova Anna, Chistyakova Victoria, Khvorostenko Denis, Kirtbaya Dmitry, Kolesnikov Gennady, Kopyltsov Evgeny, Lifirenko Igor, Lykov Alexander, Penkov Konstantin, Semenov Andrey, Shkolnik Mikhail, Skopin Pavel, Smirnov Roman, Usynin Evgeny, Varlamov Sergey, Vladimirov Vladimir, Alonso Teresa, Breijo Sara, Castro Elena, Gallardo Enrique, Banos Jose Gutierrez, Juarez Alvaro, Lozano Rebeca, Maroto Pablo, Puente Javier, Rodriguez-Vida Alejo, Girones Regina, Mellado Begona, Castellanos Enrique, Li Chunde, Chang Chao-Hsiang, Chung Hsiao-Jen, Huang Kuan-Hua, Ou Yen-Chuan, Tsai Yu-Chieh, Wang Shian-Shiang, Wu Wen-Jeng, Pang See Tong, Arslan Cagatay, Cabuk Devrim, Coskun Hasan, Gumus Mahmut, Ozguroglu Mustafa, Oksuzoglu Berna, Sahin Berksoy, Tural Deniz, Yalcin Bulent, Cicin Irfan, Bondarenko Igor, Gotsuliak Yaroslav, Hotko Yevhen, Khareba Gennadii, Lychkovskyy Oleksandr, Lytvyn Iryna, Nalbandyan Taron, Paramonov Viktor, Sakalo Valerii, Stakhovsky Eduard, Stus Viktor, Babu Sunil, Bryce Alan, Cahn David, Chao Herta, Chu Franklin, Dunshee Curtis, Goodman Oscar, Grable Michael, Hafron Jason, Hamilton Joelle, Hauke Ralph, Maly Joseph, Morris David, Newman Gregg, Pilie Patrick, Shore Neal, Sieber Paul, Smith Matthew, Trainer Andrew, Tutrone Ronald,
Affiliation:
1. BC Cancer – Vancouver Center, University of British Columbia, Vancouver, BC, Canada 2. Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, New York, NY 3. Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA 4. Houston Methodist Cancer Center, Houston, TX 5. University College London, London, UK 6. Department of Medical Oncology, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), Madrid, Spain 7. Department of Urology Cancer Center, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, South Korea 8. Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 9. Liga Norte Riograndense Contra o Câncer, Natal, Brazil 10. Department of Medical Oncology, Institut Bergonié, Bordeaux, France 11. Department of Clinical Oncology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia 12. Department of Outpatient Chemotherapy, Professor Franciszek Lukaszczyk Oncology Center, Bydgoszcz, Poland 13. Kyiv City Clinical Oncology Center and Academician O.F. Vozianov Institute of Urology of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine 14. Janssen Research & Development, LLC, Spring House, PA 15. Janssen Research & Development, LLC, Raritan, NJ 16. Janssen Research & Development, LLC, Los Angeles, CA 17. Janssen Research & Development, LLC, Titusville, NJ 18. Peter MacCallum Cancer Centre and the University of Melbourne, Melbourne, Australia
Abstract
PURPOSEMetastatic 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.METHODSMAGNITUDE (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.RESULTSMedian 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 months; HR, 0.73; 95% CI, 0.56 to 0.96; P = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR− cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events.CONCLUSIONCombination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.[Media: see text]
Publisher
American Society of Clinical Oncology (ASCO)
Subject
Cancer Research,Oncology
Cited by
129 articles.
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