Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer
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, rec...
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Other Authors: | |
Language: | en |
Published: |
MASSACHUSETTS MEDICAL SOC
2016
|
Online Access: | http://hdl.handle.net/10150/622478 http://arizona.openrepository.com/arizona/handle/10150/622478 |
id |
ndltd-arizona.edu-oai-arizona.openrepository.com-10150-622478 |
---|---|
record_format |
oai_dc |
spelling |
ndltd-arizona.edu-oai-arizona.openrepository.com-10150-6224782017-02-10T03:00:37Z Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer Mirza, Mansoor R. Monk, Bradley J. Herrstedt, Jørn Oza, Amit M. Mahner, Sven Redondo, Andrés Fabbro, Michel Ledermann, Jonathan A. Lorusso, Domenica Vergote, Ignace Ben-Baruch, Noa E. Marth, Christian Mądry, Radosław Christensen, René D. Berek, Jonathan S. Dørum, Anne Tinker, Anna V. du Bois, Andreas González-Martín, Antonio Follana, Philippe Benigno, Benedict Rosenberg, Per Gilbert, Lucy Rimel, Bobbie J. Buscema, Joseph Balser, John P. Agarwal, Shefali Matulonis, Ursula A. Univ Arizona 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.) 2016-12 Article Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer 2016, 375 (22):2154 New England Journal of Medicine 0028-4793 1533-4406 10.1056/NEJMoa1611310 http://hdl.handle.net/10150/622478 http://arizona.openrepository.com/arizona/handle/10150/622478 New England Journal of Medicine en http://www.nejm.org/doi/10.1056/NEJMoa1611310 Copyright © 2016 Massachusetts Medical Society MASSACHUSETTS MEDICAL SOC |
collection |
NDLTD |
language |
en |
sources |
NDLTD |
description |
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.) |
author2 |
Univ Arizona |
author_facet |
Univ Arizona Mirza, Mansoor R. Monk, Bradley J. Herrstedt, Jørn Oza, Amit M. Mahner, Sven Redondo, Andrés Fabbro, Michel Ledermann, Jonathan A. Lorusso, Domenica Vergote, Ignace Ben-Baruch, Noa E. Marth, Christian Mądry, Radosław Christensen, René D. Berek, Jonathan S. Dørum, Anne Tinker, Anna V. du Bois, Andreas González-Martín, Antonio Follana, Philippe Benigno, Benedict Rosenberg, Per Gilbert, Lucy Rimel, Bobbie J. Buscema, Joseph Balser, John P. Agarwal, Shefali Matulonis, Ursula A. |
author |
Mirza, Mansoor R. Monk, Bradley J. Herrstedt, Jørn Oza, Amit M. Mahner, Sven Redondo, Andrés Fabbro, Michel Ledermann, Jonathan A. Lorusso, Domenica Vergote, Ignace Ben-Baruch, Noa E. Marth, Christian Mądry, Radosław Christensen, René D. Berek, Jonathan S. Dørum, Anne Tinker, Anna V. du Bois, Andreas González-Martín, Antonio Follana, Philippe Benigno, Benedict Rosenberg, Per Gilbert, Lucy Rimel, Bobbie J. Buscema, Joseph Balser, John P. Agarwal, Shefali Matulonis, Ursula A. |
spellingShingle |
Mirza, Mansoor R. Monk, Bradley J. Herrstedt, Jørn Oza, Amit M. Mahner, Sven Redondo, Andrés Fabbro, Michel Ledermann, Jonathan A. Lorusso, Domenica Vergote, Ignace Ben-Baruch, Noa E. Marth, Christian Mądry, Radosław Christensen, René D. Berek, Jonathan S. Dørum, Anne Tinker, Anna V. du Bois, Andreas González-Martín, Antonio Follana, Philippe Benigno, Benedict Rosenberg, Per Gilbert, Lucy Rimel, Bobbie J. Buscema, Joseph Balser, John P. Agarwal, Shefali Matulonis, Ursula A. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer |
author_sort |
Mirza, Mansoor R. |
title |
Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer |
title_short |
Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer |
title_full |
Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer |
title_fullStr |
Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer |
title_full_unstemmed |
Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer |
title_sort |
niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer |
publisher |
MASSACHUSETTS MEDICAL SOC |
publishDate |
2016 |
url |
http://hdl.handle.net/10150/622478 http://arizona.openrepository.com/arizona/handle/10150/622478 |
work_keys_str_mv |
AT mirzamansoorr niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT monkbradleyj niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT herrstedtjørn niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT ozaamitm niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT mahnersven niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT redondoandres niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT fabbromichel niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT ledermannjonathana niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT lorussodomenica niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT vergoteignace niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT benbaruchnoae niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT marthchristian niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT madryradosław niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT christensenrened niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT berekjonathans niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT dørumanne niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT tinkerannav niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT duboisandreas niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT gonzalezmartinantonio niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT follanaphilippe niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT benignobenedict niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT rosenbergper niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT gilbertlucy niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT rimelbobbiej niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT buscemajoseph niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT balserjohnp niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT agarwalshefali niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer AT matulonisursulaa niraparibmaintenancetherapyinplatinumsensitiverecurrentovariancancer |
_version_ |
1718413628614377472 |