Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer

Kim N. Chi; Dana Rathkopf; Matthew R. Smith; Eleni Efstathiou; Gerhardt Attard; David Olmos; Ji Youl Lee; Eric J. Small; Andrea J. Pereira De Santana Gomes; Guilhem Roubaud; Marniza Saad; Bogdan Zurawski; Valerii Sakalo; Gary E. Mason; Peter Francis; George Wang; Daphne Wu; Brooke Diorio; Angela Lopez-Gitlitz; Shahneen Sandhu; Maria Alvarez; Gabriela Gatica; Martin Greco; Ernesto Korbenfeld; Esteban Metrebian; Jorge Salinas; Alejandro Salvatierra; Marcelo Tatangelo; Tom Ferguson; Howard Gurney; Elizabeth Hovey; Anthony Joshua; Matos Marco; Gavin Marx; Michelle Morris; Siobhan Ng; David Pook; Shahneen Sandhu; Ali Tafreshi; Thean Hsiang Tan; Tsvetanka Tosheva; Livia Andrade; Felipe Cruz; Luiza Faria; Jose Figueiredo; Fabio Franke; Andrea Juliana Gomes; Ariel Kann; Celio Kussumoto; Suelen Martins; Andre Murad; Helio Pinczowski; Giovani Pioner; Luis Pires; Daniel Preto; Gisele Santos; Eduardo Silva; Jamile Silva; Luciano Viana; Karina Vianna; Adriano Paula; Zhiwen Chen; Urban Emmenegger; Neil Fleshner; Sunil Parimi; Fred Saad; Francisco Vera-Badillo; Hongqian Guo; Hong Luo; Lulin Ma; Mingxing Qui; Wei Xue; Guo Yonglian; Lei Li; Jinxian Pu; Song Zheng; Qing Zou; Milos Brodak; Milan Hora; Vladimir Samal; Vladimir Student; Jaroslav Vanasek; Emmanuelle Bompas; Philippe Barthelemy; Delphine Borchiellini; Aude Flechon; Hakim Mahammedi; Guilhem Roubaud; Antoine Thiery-Vuillemin; Diego Tosi; Spaeth Dominique; Carole Helissey; Martin Boegemann; Susan Feyerabend; Eva Hellmis; Martin Schostak; Gerhardt Attard; Anna Lydon; Ian Sayers; Omi Parikh; Duncan Wheatley; Peter Arkosy; Jozsef Erfan; Lajos Geczi; Peter Nyirady; Judit Olah; Istvan Papos; Bela Piko; 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; Seoksoo Byun; Seol Ho Choo; Byung Ha Chung; Jaeyoung Joung; Wonho Jung; Taek Won Kang; Cheol Kwak; Tae Gyun Kwon; Hyo Jin Lee; Ji Youl Lee; Seong Il Seo; Young Deuk Choi; Hong Koo Ha; Choung Soo Kim; Flora Li Tze Chong; Chun Sen Lim; Vijayan Manogran; Hwoei Fen Soo Hoo; Guan Chou Teh; Marniza Saad; David Calvo Dominguez; Abraham Cardenas; Julia Saenz; Andre Bergman; Helgi Helgason; C. B. Hunting; Rik Somford; Tomasz Byrski; Tomasz Drewa; Dorota Filarska; Jolanta Luniewskabury; Adam Marcheluk; Konrad Talasiewicz; Krzysztof Tupikowski; Renata Zaucha; Bogdan Zurawski; Pedro Madeira; Andre Mansinho; Nuno Vau; Anna Alyasova; Victoria Chistyakova; Denis Khvorostenko; Dmitry Kirtbaya; Gennady Kolesnikov; Evgeny Kopyltsov; Igor Lifirenko; Alexander Lykov; Konstantin Penkov; Andrey Semenov; Mikhail Shkolnik; Pavel Skopin; Roman Smirnov; Evgeny Usynin; Sergey Varlamov; Vladimir Vladimirov; Teresa Alonso; Sara Breijo; Elena Castro; Enrique Gallardo; Jose Gutierrez Banos; Alvaro Juarez; Rebeca Lozano; Pablo Maroto; Javier Puente; Alejo Rodriguez-Vida; Regina Girones; Begona 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; Cagatay Arslan; Devrim Cabuk; Hasan Coskun; Mahmut Gumus; Mustafa Ozguroglu; Berna Oksuzoglu; Berksoy Sahin; Deniz Tural; Bulent Yalcin; Irfan Cicin; Igor Bondarenko; Yaroslav Gotsuliak; Yevhen Hotko; Gennadii Khareba; Oleksandr Lychkovskyy; Iryna Lytvyn; Taron Nalbandyan; Viktor Paramonov; Valerii Sakalo; Eduard Stakhovsky; Viktor Stus; Sunil Babu; Alan Bryce; David Cahn; Herta Chao; Franklin Chu; Curtis Dunshee; Oscar Goodman; Michael Grable; Jason Hafron; Joelle Hamilton; Ralph Hauke; Joseph Maly; David Morris; Gregg Newman; Patrick Pilie; Neal Shore; Paul Sieber; Matthew Smith; Andrew Trainer; Ronald Tutrone

doi:10.1200/JCO.22.01649

Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer

Kim N. Chi, Dana Rathkopf, Matthew R. Smith, Eleni Efstathiou, Gerhardt Attard, David Olmos, Ji Youl Lee, Eric J. Small, Andrea J. Pereira De Santana Gomes, Guilhem Roubaud, Marniza Saad, Bogdan Zurawski, Valerii Sakalo, Gary E. Mason, Peter Francis, George Wang, Daphne Wu, Brooke Diorio, Angela Lopez-Gitlitz, Shahneen SandhuMaria Alvarez, Gabriela Gatica, Martin Greco, Ernesto Korbenfeld, Esteban Metrebian, Jorge Salinas, Alejandro Salvatierra, Marcelo Tatangelo, Tom Ferguson, Howard Gurney, Elizabeth Hovey, Anthony Joshua, Matos Marco, Gavin Marx, Michelle Morris, Siobhan Ng, David Pook, Shahneen Sandhu, Ali Tafreshi, Thean Hsiang Tan, Tsvetanka Tosheva, Livia Andrade, Felipe Cruz, Luiza Faria, Jose Figueiredo, Fabio Franke, Andrea Juliana Gomes, Ariel Kann, Celio Kussumoto, Suelen Martins, Andre Murad, Helio Pinczowski, Giovani Pioner, Luis Pires, Daniel Preto, Gisele Santos, Eduardo Silva, Jamile Silva, Luciano Viana, Karina Vianna, Adriano Paula, Zhiwen Chen, Urban Emmenegger, Neil Fleshner, Sunil Parimi, Fred Saad, Francisco Vera-Badillo, Hongqian Guo, Hong Luo, Lulin Ma, Mingxing Qui, Wei Xue, Guo Yonglian, Lei Li, Jinxian Pu, Song Zheng, Qing Zou, Milos Brodak, Milan Hora, Vladimir Samal, Vladimir Student, Jaroslav Vanasek, Emmanuelle Bompas, Philippe Barthelemy, Delphine Borchiellini, Aude Flechon, Hakim Mahammedi, Guilhem Roubaud, Antoine Thiery-Vuillemin, Diego Tosi, Spaeth Dominique, Carole Helissey, Martin Boegemann, Susan Feyerabend, Eva Hellmis, Martin Schostak, Gerhardt Attard, Anna Lydon, Ian Sayers, Omi Parikh, Duncan Wheatley, Peter Arkosy, Jozsef Erfan, Lajos Geczi, Peter Nyirady, Judit Olah, Istvan Papos, Bela Piko, 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, Seoksoo Byun, Seol Ho Choo, Byung Ha Chung, Jaeyoung Joung, Wonho Jung, Taek Won Kang, Cheol Kwak, Tae Gyun Kwon, Hyo Jin Lee, Ji Youl Lee, Seong Il Seo, Young Deuk Choi, Hong Koo Ha, Choung Soo Kim, Flora Li Tze Chong, Chun Sen Lim, Vijayan Manogran, Hwoei Fen Soo Hoo, Guan Chou Teh, Marniza Saad, David Calvo Dominguez, Abraham Cardenas, Julia Saenz, Andre Bergman, Helgi Helgason, C. B. Hunting, Rik Somford, Tomasz Byrski, Tomasz Drewa, Dorota Filarska, Jolanta Luniewskabury, Adam Marcheluk, Konrad Talasiewicz, Krzysztof Tupikowski, Renata Zaucha, Bogdan Zurawski, Pedro Madeira, Andre Mansinho, Nuno Vau, Anna Alyasova, Victoria Chistyakova, Denis Khvorostenko, Dmitry Kirtbaya, Gennady Kolesnikov, Evgeny Kopyltsov, Igor Lifirenko, Alexander Lykov, Konstantin Penkov, Andrey Semenov, Mikhail Shkolnik, Pavel Skopin, Roman Smirnov, Evgeny Usynin, Sergey Varlamov, Vladimir Vladimirov, Teresa Alonso, Sara Breijo, Elena Castro, Enrique Gallardo, Jose Gutierrez Banos, Alvaro Juarez, Rebeca Lozano, Pablo Maroto, Javier Puente, Alejo Rodriguez-Vida, Regina Girones, Begona 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, Cagatay Arslan, Devrim Cabuk, Hasan Coskun, Mahmut Gumus, Mustafa Ozguroglu, Berna Oksuzoglu, Berksoy Sahin, Deniz Tural, Bulent Yalcin, Irfan Cicin, Igor Bondarenko, Yaroslav Gotsuliak, Yevhen Hotko, Gennadii Khareba, Oleksandr Lychkovskyy, Iryna Lytvyn, Taron Nalbandyan, Viktor Paramonov, Valerii Sakalo, Eduard Stakhovsky, Viktor Stus, Sunil Babu, Alan Bryce, David Cahn, Herta Chao, Franklin Chu, Curtis Dunshee, Oscar Goodman, Michael Grable, Jason Hafron, Joelle Hamilton, Ralph Hauke, Joseph Maly, David Morris, Gregg Newman, Patrick Pilie, Neal Shore, Paul Sieber, Matthew Smith, Andrew Trainer, Ronald Tutrone

Hematology/Oncology

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	3339-3351
Number of pages	13
Journal	Journal of Clinical Oncology
Volume	41
Issue number	18
DOIs	https://doi.org/10.1200/JCO.22.01649
State	Published - Jun 20 2023

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.1200/JCO.22.01649

Cite this

Chi, K. N., Rathkopf, D., Smith, M. R., Efstathiou, E., Attard, G., Olmos, D., Lee, J. Y., Small, E. J., Pereira De Santana Gomes, A. J., Roubaud, G., Saad, M., Zurawski, B., Sakalo, V., Mason, G. E., Francis, P., Wang, G., Wu, D., Diorio, B., Lopez-Gitlitz, A., ... Tutrone, R. (2023). Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer. Journal of Clinical Oncology, 41(18), 3339-3351. https://doi.org/10.1200/JCO.22.01649

Chi, KN, Rathkopf, D, Smith, MR, Efstathiou, E, Attard, G, Olmos, D, Lee, JY, Small, EJ, Pereira De Santana Gomes, AJ, Roubaud, G, Saad, M, Zurawski, B, Sakalo, V, Mason, GE, Francis, P, Wang, G, Wu, D, Diorio, B, Lopez-Gitlitz, A, Sandhu, S, Alvarez, M, Gatica, G, Greco, M, Korbenfeld, E, Metrebian, E, Salinas, J, Salvatierra, A, Tatangelo, M, Ferguson, T, Gurney, H, Hovey, E, Joshua, A, Marco, M, Marx, G, Morris, M, Ng, S, Pook, D, Sandhu, S, Tafreshi, A, Tan, TH, Tosheva, T, Andrade, L, Cruz, F, Faria, L, Figueiredo, J, Franke, F, Gomes, AJ, Kann, A, Kussumoto, C, Martins, S, Murad, A, Pinczowski, H, Pioner, G, Pires, L, Preto, D, Santos, G, Silva, E, Silva, J, Viana, L, Vianna, K, Paula, A, Chen, Z, Emmenegger, U, Fleshner, N, Parimi, S, Saad, F, Vera-Badillo, F, Guo, H, Luo, H, Ma, L, Qui, M, Xue, W, Yonglian, G, Li, L, Pu, J, Zheng, S, Zou, Q, Brodak, M, Hora, M, Samal, V, Student, V, Vanasek, J, Bompas, E, Barthelemy, P, Borchiellini, D, Flechon, A, Mahammedi, H, Roubaud, G, Thiery-Vuillemin, A, Tosi, D, Dominique, S, Helissey, C, Boegemann, M, Feyerabend, S, Hellmis, E, Schostak, M, Attard, G, Lydon, A, Sayers, I, Parikh, O, Wheatley, D, Arkosy, P, Erfan, J, Geczi, L, Nyirady, P, Olah, J, Papos, I, Piko, B, Berger, R, Peer, A, Basso, U, Bracarda, S, Caffo, O, Carrozza, F, Del Conte, G, Galli, L, Gasparro, D, Pignata, S, Ricotta, R, Santini, D, Tortora, G, Byun, S, Choo, SH, Chung, BH, Joung, J, Jung, W, Kang, TW, Kwak, C, Kwon, TG, Lee, HJ, Lee, JY, Seo, SI, Choi, YD, Ha, HK, Kim, CS, Tze Chong, FL, Lim, CS, Manogran, V, Soo Hoo, HF, Teh, GC, Saad, M, Dominguez, DC, Cardenas, A, Saenz, J, Bergman, A, Helgason, H, Hunting, CB, Somford, R, Byrski, T, Drewa, T, Filarska, D, Luniewskabury, J, Marcheluk, A, Talasiewicz, K, Tupikowski, K, Zaucha, R, Zurawski, B, Madeira, P, Mansinho, A, Vau, N, Alyasova, A, Chistyakova, V, Khvorostenko, D, Kirtbaya, D, Kolesnikov, G, Kopyltsov, E, Lifirenko, I, Lykov, A, Penkov, K, Semenov, A, Shkolnik, M, Skopin, P, Smirnov, R, Usynin, E, Varlamov, S, Vladimirov, V, Alonso, T, Breijo, S, Castro, E, Gallardo, E, Banos, JG, Juarez, A, Lozano, R, Maroto, P, Puente, J, Rodriguez-Vida, A, Girones, R, Mellado, B, Castellanos, E, Li, C, Chang, CH, Chung, HJ, Huang, KH, Ou, YC, Tsai, YC, Wang, SS, Wu, WJ, Pang, ST, Arslan, C, Cabuk, D, Coskun, H, Gumus, M, Ozguroglu, M, Oksuzoglu, B, Sahin, B, Tural, D, Yalcin, B, Cicin, I, Bondarenko, I, Gotsuliak, Y, Hotko, Y, Khareba, G, Lychkovskyy, O, Lytvyn, I, Nalbandyan, T, Paramonov, V, Sakalo, V, Stakhovsky, E, Stus, V, Babu, S, Bryce, A, Cahn, D, Chao, H, Chu, F, Dunshee, C, Goodman, O, Grable, M, Hafron, J, Hamilton, J, Hauke, R, Maly, J, Morris, D, Newman, G, Pilie, P, Shore, N, Sieber, P, Smith, M, Trainer, A & Tutrone, R 2023, 'Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer', Journal of Clinical Oncology, vol. 41, no. 18, pp. 3339-3351. https://doi.org/10.1200/JCO.22.01649

@article{723fc2d1814e4cd4a08459c29c4f7c76,

title = "Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer",

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-na{\"i}ve 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.",

author = "Chi, {Kim N.} and Dana Rathkopf and Smith, {Matthew R.} and Eleni Efstathiou and Gerhardt Attard and David Olmos and Lee, {Ji Youl} and Small, {Eric J.} and {Pereira De Santana Gomes}, {Andrea J.} and Guilhem Roubaud and Marniza Saad and Bogdan Zurawski and Valerii Sakalo and Mason, {Gary E.} and Peter Francis and George Wang and Daphne Wu and Brooke Diorio and Angela Lopez-Gitlitz and Shahneen Sandhu and Maria Alvarez and Gabriela Gatica and Martin Greco and Ernesto Korbenfeld and Esteban Metrebian and Jorge Salinas and Alejandro Salvatierra and Marcelo Tatangelo and Tom Ferguson and Howard Gurney and Elizabeth Hovey and Anthony Joshua and Matos Marco and Gavin Marx and Michelle Morris and Siobhan Ng and David Pook and Shahneen Sandhu and Ali Tafreshi and Tan, {Thean Hsiang} and Tsvetanka Tosheva and Livia Andrade and Felipe Cruz and Luiza Faria and Jose Figueiredo and Fabio Franke and Gomes, {Andrea Juliana} and Ariel Kann and Celio Kussumoto and Suelen Martins and Andre Murad and Helio Pinczowski and Giovani Pioner and Luis Pires and Daniel Preto and Gisele Santos and Eduardo Silva and Jamile Silva and Luciano Viana and Karina Vianna and Adriano Paula and Zhiwen Chen and Urban Emmenegger and Neil Fleshner and Sunil Parimi and Fred Saad and Francisco Vera-Badillo and Hongqian Guo and Hong Luo and Lulin Ma and Mingxing Qui and Wei Xue and Guo Yonglian and Lei Li and Jinxian Pu and Song Zheng and Qing Zou and Milos Brodak and Milan Hora and Vladimir Samal and Vladimir Student and Jaroslav Vanasek and Emmanuelle Bompas and Philippe Barthelemy and Delphine Borchiellini and Aude Flechon and Hakim Mahammedi and Guilhem Roubaud and Antoine Thiery-Vuillemin and Diego Tosi and Spaeth Dominique and Carole Helissey and Martin Boegemann and Susan Feyerabend and Eva Hellmis and Martin Schostak and Gerhardt Attard and Anna Lydon and Ian Sayers and Omi Parikh and Duncan Wheatley and Peter Arkosy and Jozsef Erfan and Lajos Geczi and Peter Nyirady and Judit Olah and Istvan Papos and Bela Piko and Raanan Berger and Avivit Peer and Umberto Basso and Sergio Bracarda and Orazio Caffo and Francesco Carrozza and {Del Conte}, Gianluca and Luca Galli and Donatello Gasparro and Sandro Pignata and Riccardo Ricotta and Daniele Santini and Giampaolo Tortora and Seoksoo Byun and Choo, {Seol Ho} and Chung, {Byung Ha} and Jaeyoung Joung and Wonho Jung and Kang, {Taek Won} and Cheol Kwak and Kwon, {Tae Gyun} and Lee, {Hyo Jin} and Lee, {Ji Youl} and Seo, {Seong Il} and Choi, {Young Deuk} and Ha, {Hong Koo} and Kim, {Choung Soo} and {Tze Chong}, {Flora Li} and Lim, {Chun Sen} and Vijayan Manogran and {Soo Hoo}, {Hwoei Fen} and Teh, {Guan Chou} and Marniza Saad and Dominguez, {David Calvo} and Abraham Cardenas and Julia Saenz and Andre Bergman and Helgi Helgason and Hunting, {C. B.} and Rik Somford and Tomasz Byrski and Tomasz Drewa and Dorota Filarska and Jolanta Luniewskabury and Adam Marcheluk and Konrad Talasiewicz and Krzysztof Tupikowski and Renata Zaucha and Bogdan Zurawski and Pedro Madeira and Andre Mansinho and Nuno Vau and Anna Alyasova and Victoria Chistyakova and Denis Khvorostenko and Dmitry Kirtbaya and Gennady Kolesnikov and Evgeny Kopyltsov and Igor Lifirenko and Alexander Lykov and Konstantin Penkov and Andrey Semenov and Mikhail Shkolnik and Pavel Skopin and Roman Smirnov and Evgeny Usynin and Sergey Varlamov and Vladimir Vladimirov and Teresa Alonso and Sara Breijo and Elena Castro and Enrique Gallardo and Banos, {Jose Gutierrez} and Alvaro Juarez and Rebeca Lozano and Pablo Maroto and Javier Puente and Alejo Rodriguez-Vida and Regina Girones and Begona Mellado and Enrique Castellanos and Chunde Li and Chang, {Chao Hsiang} and Chung, {Hsiao Jen} and Huang, {Kuan Hua} and Ou, {Yen Chuan} and Tsai, {Yu Chieh} and Wang, {Shian Shiang} and Wu, {Wen Jeng} and Pang, {See Tong} and Cagatay Arslan and Devrim Cabuk and Hasan Coskun and Mahmut Gumus and Mustafa Ozguroglu and Berna Oksuzoglu and Berksoy Sahin and Deniz Tural and Bulent Yalcin and Irfan Cicin and Igor Bondarenko and Yaroslav Gotsuliak and Yevhen Hotko and Gennadii Khareba and Oleksandr Lychkovskyy and Iryna Lytvyn and Taron Nalbandyan and Viktor Paramonov and Valerii Sakalo and Eduard Stakhovsky and Viktor Stus and Sunil Babu and Alan Bryce and David Cahn and Herta Chao and Franklin Chu and Curtis Dunshee and Oscar Goodman and Michael Grable and Jason Hafron and Joelle Hamilton and Ralph Hauke and Joseph Maly and David Morris and Gregg Newman and Patrick Pilie and Neal Shore and Paul Sieber and Matthew Smith and Andrew Trainer and Ronald Tutrone",

note = "Publisher Copyright: {\textcopyright} American Society of Clinical Oncology.",

year = "2023",

month = jun,

day = "20",

doi = "10.1200/JCO.22.01649",

language = "English (US)",

volume = "41",

pages = "3339--3351",

journal = "Journal of Clinical Oncology",

issn = "0732-183X",

publisher = "American Society of Clinical Oncology",

number = "18",

}

TY - JOUR

T1 - Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer

AU - Chi, Kim N.

AU - Rathkopf, Dana

AU - Smith, Matthew R.

AU - Efstathiou, Eleni

AU - Attard, Gerhardt

AU - Olmos, David

AU - Lee, Ji Youl

AU - Small, Eric J.

AU - Pereira De Santana Gomes, Andrea J.

AU - Roubaud, Guilhem

AU - Saad, Marniza

AU - Zurawski, Bogdan

AU - Sakalo, Valerii

AU - Mason, Gary E.

AU - Francis, Peter

AU - Wang, George

AU - Wu, Daphne

AU - Diorio, Brooke

AU - Lopez-Gitlitz, Angela

AU - Sandhu, Shahneen

AU - Alvarez, Maria

AU - Gatica, Gabriela

AU - Greco, Martin

AU - Korbenfeld, Ernesto

AU - Metrebian, Esteban

AU - Salinas, Jorge

AU - Salvatierra, Alejandro

AU - Tatangelo, Marcelo

AU - Ferguson, Tom

AU - Gurney, Howard

AU - Hovey, Elizabeth

AU - Joshua, Anthony

AU - Marco, Matos

AU - Marx, Gavin

AU - Morris, Michelle

AU - Ng, Siobhan

AU - Pook, David

AU - Sandhu, Shahneen

AU - Tafreshi, Ali

AU - Tan, Thean Hsiang

AU - Tosheva, Tsvetanka

AU - Andrade, Livia

AU - Cruz, Felipe

AU - Faria, Luiza

AU - Figueiredo, Jose

AU - Franke, Fabio

AU - Gomes, Andrea Juliana

AU - Kann, Ariel

AU - Kussumoto, Celio

AU - Martins, Suelen

AU - Murad, Andre

AU - Pinczowski, Helio

AU - Pioner, Giovani

AU - Pires, Luis

AU - Preto, Daniel

AU - Santos, Gisele

AU - Silva, Eduardo

AU - Silva, Jamile

AU - Viana, Luciano

AU - Vianna, Karina

AU - Paula, Adriano

AU - Chen, Zhiwen

AU - Emmenegger, Urban

AU - Fleshner, Neil

AU - Parimi, Sunil

AU - Saad, Fred

AU - Vera-Badillo, Francisco

AU - Guo, Hongqian

AU - Luo, Hong

AU - Ma, Lulin

AU - Qui, Mingxing

AU - Xue, Wei

AU - Yonglian, Guo

AU - Li, Lei

AU - Pu, Jinxian

AU - Zheng, Song

AU - Zou, Qing

AU - Brodak, Milos

AU - Hora, Milan

AU - Samal, Vladimir

AU - Student, Vladimir

AU - Vanasek, Jaroslav

AU - Bompas, Emmanuelle

AU - Barthelemy, Philippe

AU - Borchiellini, Delphine

AU - Flechon, Aude

AU - Mahammedi, Hakim

AU - Roubaud, Guilhem

AU - Thiery-Vuillemin, Antoine

AU - Tosi, Diego

AU - Dominique, Spaeth

AU - Helissey, Carole

AU - Boegemann, Martin

AU - Feyerabend, Susan

AU - Hellmis, Eva

AU - Schostak, Martin

AU - Attard, Gerhardt

AU - Lydon, Anna

AU - Sayers, Ian

AU - Parikh, Omi

AU - Wheatley, Duncan

AU - Arkosy, Peter

AU - Erfan, Jozsef

AU - Geczi, Lajos

AU - Nyirady, Peter

AU - Olah, Judit

AU - Papos, Istvan

AU - Piko, Bela

AU - Berger, Raanan

AU - Peer, Avivit

AU - Basso, Umberto

AU - Bracarda, Sergio

AU - Caffo, Orazio

AU - Carrozza, Francesco

AU - Del Conte, Gianluca

AU - Galli, Luca

AU - Gasparro, Donatello

AU - Pignata, Sandro

AU - Ricotta, Riccardo

AU - Santini, Daniele

AU - Tortora, Giampaolo

AU - Byun, Seoksoo

AU - Choo, Seol Ho

AU - Chung, Byung Ha

AU - Joung, Jaeyoung

AU - Jung, Wonho

AU - Kang, Taek Won

AU - Kwak, Cheol

AU - Kwon, Tae Gyun

AU - Lee, Hyo Jin

AU - Lee, Ji Youl

AU - Seo, Seong Il

AU - Choi, Young Deuk

AU - Ha, Hong Koo

AU - Kim, Choung Soo

AU - Tze Chong, Flora Li

AU - Lim, Chun Sen

AU - Manogran, Vijayan

AU - Soo Hoo, Hwoei Fen

AU - Teh, Guan Chou

AU - Saad, Marniza

AU - Dominguez, David Calvo

AU - Cardenas, Abraham

AU - Saenz, Julia

AU - Bergman, Andre

AU - Helgason, Helgi

AU - Hunting, C. B.

AU - Somford, Rik

AU - Byrski, Tomasz

AU - Drewa, Tomasz

AU - Filarska, Dorota

AU - Luniewskabury, Jolanta

AU - Marcheluk, Adam

AU - Talasiewicz, Konrad

AU - Tupikowski, Krzysztof

AU - Zaucha, Renata

AU - Zurawski, Bogdan

AU - Madeira, Pedro

AU - Mansinho, Andre

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AU - Alyasova, Anna

AU - Chistyakova, Victoria

AU - Khvorostenko, Denis

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AU - Kolesnikov, Gennady

AU - Kopyltsov, Evgeny

AU - Lifirenko, Igor

AU - Lykov, Alexander

AU - Penkov, Konstantin

AU - Semenov, Andrey

AU - Shkolnik, Mikhail

AU - Skopin, Pavel

AU - Smirnov, Roman

AU - Usynin, Evgeny

AU - Varlamov, Sergey

AU - Vladimirov, Vladimir

AU - Alonso, Teresa

AU - Breijo, Sara

AU - Castro, Elena

AU - Gallardo, Enrique

AU - Banos, Jose Gutierrez

AU - Juarez, Alvaro

AU - Lozano, Rebeca

AU - Maroto, Pablo

AU - Puente, Javier

AU - Rodriguez-Vida, Alejo

AU - Girones, Regina

AU - Mellado, Begona

AU - Castellanos, Enrique

AU - Li, Chunde

AU - Chang, Chao Hsiang

AU - Chung, Hsiao Jen

AU - Huang, Kuan Hua

AU - Ou, Yen Chuan

AU - Tsai, Yu Chieh

AU - Wang, Shian Shiang

AU - Wu, Wen Jeng

AU - Pang, See Tong

AU - Arslan, Cagatay

AU - Cabuk, Devrim

AU - Coskun, Hasan

AU - Gumus, Mahmut

AU - Ozguroglu, Mustafa

AU - Oksuzoglu, Berna

AU - Sahin, Berksoy

AU - Tural, Deniz

AU - Yalcin, Bulent

AU - Cicin, Irfan

AU - Bondarenko, Igor

AU - Gotsuliak, Yaroslav

AU - Hotko, Yevhen

AU - Khareba, Gennadii

AU - Lychkovskyy, Oleksandr

AU - Lytvyn, Iryna

AU - Nalbandyan, Taron

AU - Paramonov, Viktor

AU - Sakalo, Valerii

AU - Stakhovsky, Eduard

AU - Stus, Viktor

AU - Babu, Sunil

AU - Bryce, Alan

AU - Cahn, David

AU - Chao, Herta

AU - Chu, Franklin

AU - Dunshee, Curtis

AU - Goodman, Oscar

AU - Grable, Michael

AU - Hafron, Jason

AU - Hamilton, Joelle

AU - Hauke, Ralph

AU - Maly, Joseph

AU - Morris, David

AU - Newman, Gregg

AU - Pilie, Patrick

AU - Shore, Neal

AU - Sieber, Paul

AU - Smith, Matthew

AU - Trainer, Andrew

AU - Tutrone, Ronald

PY - 2023/6/20

Y1 - 2023/6/20

N2 - 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.

AB - 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.

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U2 - 10.1200/JCO.22.01649

DO - 10.1200/JCO.22.01649

M3 - Article

C2 - 36952634

AN - SCOPUS:85161255306

SN - 0732-183X

VL - 41

SP - 3339

EP - 3351

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

IS - 18

ER -

Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer

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