Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer
Mansoor R Mirza, Bradley J Monk, Jørn Herrstedt, Amit M Oza, Sven Mahner, Andrés Redondo, Michel Fabbro, Jonathan A Ledermann, Domenica Lorusso, Ignace Vergote, Noa E Ben-Baruch, Christian Marth, Radosław Mądry, René D Christensen, Jonathan S Berek, Anne Dørum, Anna V Tinker, Andreas du Bois, Antonio González-Martín, Philippe Follana, Benedict Benigno, Per Rosenberg, Lucy Gilbert, Bobbie J Rimel, Joseph Buscema, John P Balser, Shefali Agarwal, Ursula A Matulonis, ENGOT-OV16/NOVA Investigators, Bente Lund, Susanne Malander, Kathrine Woie, Kristina Hellman, Trine Juhler Nøttrup, Hanne Havsteen, Jalid Sehouli, Philipp Harter, Ulrich Canzler, Hans-Joachim Lück, Linn Wölber, Frederik Marmé, Werner Meier, Martin Heubner, Felix Hilpert, Günter Emons, Alexander Burges, Isabel Maria Bover Barcelo, Marta Gil Martín, Isabel Palacio Vázquez, Antonio Casado Herráez, José Maria del Campo, Anne Lesoin, Dominique Berton-Rigaud, Thierry N’Guyen, Anne-Claire Hardy-Bessard, Susana Banerjee, Rosemary Lord, Justin Waters, Ana Montes, Stephen Chan, Sarah J Williams, Claire Barlow, Anna Mullard, Nicoletta Colombo, Giovanni Scambia, Germana Tognon, Paolo Scollo, Frédéric Kridelka, Chantal Leroy, Philip Debruyne, Manon Huizing, Ora Rosengarten, Talia Levy, Ronnie Shapira Frommer, Ami Fishman, David Edelman, Tamar Safra, Amnon Amit, Joanna Pikiel, Jacek Suzin, Beata Mackowiak-Matejczyk, Alexander Reinthaller, Edgar Petru, Tibor Csoszi, Paul Bessette, Diane Provencher, Susie Lau, Susan Ellard, Prafull Ghatage, Kathleen Moore, Robert Wenham, Mario Pineda, Masoud Azodi, Gina Mantia-Smaldone, Noelle Cloven, Cheryl Bailey, Christine Lee, Angeles Secord, Manish Patel, Michael Method, Michael Callahan, John Veena, John Chan, Corrine Zarwan, Paul DiSilvestro, Michael Teneriello, Divya Gupta, Melissa Geller, Howard Burris, Brian Slomovitz, Andrea Wahner Hendrickson, Colleen McCormick, Parviz Hanjani, Stephanie Blank, Paul Haluska, Daniela Matei, Stephen Vasilev, Jeffrey Neidhart, Matthew Boente, Nana Tchabo, David Miller, Mansoor R Mirza, Bradley J Monk, Jørn Herrstedt, Amit M Oza, Sven Mahner, Andrés Redondo, Michel Fabbro, Jonathan A Ledermann, Domenica Lorusso, Ignace Vergote, Noa E Ben-Baruch, Christian Marth, Radosław Mądry, René D Christensen, Jonathan S Berek, Anne Dørum, Anna V Tinker, Andreas du Bois, Antonio González-Martín, Philippe Follana, Benedict Benigno, Per Rosenberg, Lucy Gilbert, Bobbie J Rimel, Joseph Buscema, John P Balser, Shefali Agarwal, Ursula A Matulonis, ENGOT-OV16/NOVA Investigators, Bente Lund, Susanne Malander, Kathrine Woie, Kristina Hellman, Trine Juhler Nøttrup, Hanne Havsteen, Jalid Sehouli, Philipp Harter, Ulrich Canzler, Hans-Joachim Lück, Linn Wölber, Frederik Marmé, Werner Meier, Martin Heubner, Felix Hilpert, Günter Emons, Alexander Burges, Isabel Maria Bover Barcelo, Marta Gil Martín, Isabel Palacio Vázquez, Antonio Casado Herráez, José Maria del Campo, Anne Lesoin, Dominique Berton-Rigaud, Thierry N’Guyen, Anne-Claire Hardy-Bessard, Susana Banerjee, Rosemary Lord, Justin Waters, Ana Montes, Stephen Chan, Sarah J Williams, Claire Barlow, Anna Mullard, Nicoletta Colombo, Giovanni Scambia, Germana Tognon, Paolo Scollo, Frédéric Kridelka, Chantal Leroy, Philip Debruyne, Manon Huizing, Ora Rosengarten, Talia Levy, Ronnie Shapira Frommer, Ami Fishman, David Edelman, Tamar Safra, Amnon Amit, Joanna Pikiel, Jacek Suzin, Beata Mackowiak-Matejczyk, Alexander Reinthaller, Edgar Petru, Tibor Csoszi, Paul Bessette, Diane Provencher, Susie Lau, Susan Ellard, Prafull Ghatage, Kathleen Moore, Robert Wenham, Mario Pineda, Masoud Azodi, Gina Mantia-Smaldone, Noelle Cloven, Cheryl Bailey, Christine Lee, Angeles Secord, Manish Patel, Michael Method, Michael Callahan, John Veena, John Chan, Corrine Zarwan, Paul DiSilvestro, Michael Teneriello, Divya Gupta, Melissa Geller, Howard Burris, Brian Slomovitz, Andrea Wahner Hendrickson, Colleen McCormick, Parviz Hanjani, Stephanie Blank, Paul Haluska, Daniela Matei, Stephen Vasilev, Jeffrey Neidhart, Matthew Boente, Nana Tchabo, David Miller
Abstract
Background: Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer.
Methods: In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival.
Results: Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P<0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications.
Conclusions: Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by Tesaro; ClinicalTrials.gov number, NCT01847274 .).
Source: PubMed