Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer
Authors: Chi Kim N. , Rathkopf Dana , Smith Matthew R. , Efstathiou Eleni , Attard Gerhardt , Olmos David , Lee Ji Youl , Small Eric J. , Pereira de Santana Gomes Andrea J. , Roubaud Guilhem , Saad Marniza , Zurawski Bogdan , Sakalo Valerii , Mason Gary E. , Francis Peter , Wang George , Wu Daphne , Diorio Brooke , Lopez-Gitlitz Angela , Sandhu Shahneen ,   on behalf of the MAGNITUDE Principal Investigators, 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 
Published: March 2023

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]