Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer.
Administration, Oral
Adult
Aged
Aged, 80 and over
Antineoplastic Agents
/ therapeutic use
Combined Modality Therapy
Double-Blind Method
Female
Humans
Indazoles
/ adverse effects
Maintenance Chemotherapy
Middle Aged
Nausea
/ chemically induced
Ovarian Neoplasms
/ drug therapy
Piperidines
/ adverse effects
Poly(ADP-ribose) Polymerase Inhibitors
/ adverse effects
Progression-Free Survival
Quality of Life
Survival Analysis
Journal
The New England journal of medicine
ISSN: 1533-4406
Titre abrégé: N Engl J Med
Pays: United States
ID NLM: 0255562
Informations de publication
Date de publication:
19 12 2019
19 12 2019
Historique:
pubmed:
29
9
2019
medline:
24
12
2019
entrez:
29
9
2019
Statut:
ppublish
Résumé
Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients with recurrent ovarian cancer after platinum-based chemotherapy, regardless of the presence or absence of In this randomized, double-blind, phase 3 trial, we randomly assigned patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy. The primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. A prespecified interim analysis for overall survival was conducted at the time of the primary analysis of progression-free survival. Of the 733 patients who underwent randomization, 373 (50.9%) had tumors with homologous-recombination deficiency. Among the patients in this category, the median progression-free survival was significantly longer in the niraparib group than in the placebo group (21.9 months vs. 10.4 months; hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001). In the overall population, the corresponding progression-free survival was 13.8 months and 8.2 months (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (hazard ratio, 0.70; 95% CI, 0.44 to 1.11). The most common adverse events of grade 3 or higher were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). No treatment-related deaths occurred. Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. (Funded by GlaxoSmithKline; PRIMA/ENGOT-OV26/GOG-3012 ClinicalTrials.gov number, NCT02655016.).
Sections du résumé
BACKGROUND
Niraparib, an inhibitor of poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP), has been associated with significantly increased progression-free survival among patients with recurrent ovarian cancer after platinum-based chemotherapy, regardless of the presence or absence of
METHODS
In this randomized, double-blind, phase 3 trial, we randomly assigned patients with newly diagnosed advanced ovarian cancer in a 2:1 ratio to receive niraparib or placebo once daily after a response to platinum-based chemotherapy. The primary end point was progression-free survival in patients who had tumors with homologous-recombination deficiency and in those in the overall population, as determined on hierarchical testing. A prespecified interim analysis for overall survival was conducted at the time of the primary analysis of progression-free survival.
RESULTS
Of the 733 patients who underwent randomization, 373 (50.9%) had tumors with homologous-recombination deficiency. Among the patients in this category, the median progression-free survival was significantly longer in the niraparib group than in the placebo group (21.9 months vs. 10.4 months; hazard ratio for disease progression or death, 0.43; 95% confidence interval [CI], 0.31 to 0.59; P<0.001). In the overall population, the corresponding progression-free survival was 13.8 months and 8.2 months (hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). At the 24-month interim analysis, the rate of overall survival was 84% in the niraparib group and 77% in the placebo group (hazard ratio, 0.70; 95% CI, 0.44 to 1.11). The most common adverse events of grade 3 or higher were anemia (in 31.0% of the patients), thrombocytopenia (in 28.7%), and neutropenia (in 12.8%). No treatment-related deaths occurred.
CONCLUSIONS
Among patients with newly diagnosed advanced ovarian cancer who had a response to platinum-based chemotherapy, those who received niraparib had significantly longer progression-free survival than those who received placebo, regardless of the presence or absence of homologous-recombination deficiency. (Funded by GlaxoSmithKline; PRIMA/ENGOT-OV26/GOG-3012 ClinicalTrials.gov number, NCT02655016.).
Identifiants
pubmed: 31562799
doi: 10.1056/NEJMoa1910962
doi:
Substances chimiques
Antineoplastic Agents
0
Indazoles
0
Piperidines
0
Poly(ADP-ribose) Polymerase Inhibitors
0
niraparib
HMC2H89N35
Banques de données
ClinicalTrials.gov
['NCT02655016']
Types de publication
Clinical Trial, Phase III
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2391-2402Investigateurs
Jean-Francois Baurain
(JF)
Hannelore Denys
(H)
Brigitte Honhon
(B)
Heidi Van Den Bulck
(H)
Sileny Han
(S)
Eric Joosens
(E)
Peter Vuylsteke
(P)
Frederic Forget
(F)
Caroline Lamot
(C)
Corina Martinez Mena
(C)
Ulla Peen
(U)
Anja Knudsen
(A)
Johanna Maenpaa
(J)
Sakari Hietanen
(S)
Maarit Anttila
(M)
Ulla Puistola
(U)
Michel Fabbro
(M)
Philippe Follana
(P)
Frederic Selle
(F)
Florence Joly-Lobbedez
(F)
Thibault De La Motte Rouge
(T)
Dominique Berton-Rigaud
(D)
Sophie Abadie Lacourtoisie
(S)
Ioana Braicu
(I)
Volker Hanf
(V)
Florian Heitz
(F)
Frederik Marme
(F)
Andreas Schneeweiss
(A)
Alexander Burges
(A)
Barbara Schmalfeldt
(B)
Gunter Emons
(G)
Paula M Calvert
(PM)
Jacob Korach
(J)
Talia Levy
(T)
Amnon Amit
(A)
Tamar Safra
(T)
Grazia Artioli
(G)
Francesco Raspagliesi
(F)
Carmela Pisano
(C)
Sabino De Placido
(S)
Roberto Sabbatini
(R)
Giorgio Valabrega
(G)
Ana Oaknin
(A)
Eva Guerra
(E)
Cristina Churruca
(C)
Raquel Bratos
(R)
Jose Perez
(J)
Ignacio Romero
(I)
Ignacio Tusquets
(I)
Lydia Gaba Garcia
(L)
Marta Gil Martin
(M)
Elisa Calvo-Garcia
(E)
Luis Manso Sanchez
(L)
Jose Fuentes Pradera
(J)
Ana Sanchez-Heras
(A)
Alfonso Yubero
(A)
Margarita Romeo-Marin
(M)
Kristina Hellman
(K)
Bengt Tholander
(B)
David Cibula
(D)
Lukas Rob
(L)
Denis Berezovskiy
(D)
Meinolf Karthaus
(M)
Robert Poka
(R)
Tamas Pinter
(T)
Paul Donnellan
(P)
Mihai Meirovitz
(M)
Anne Dorum
(A)
Radoslaw Madry
(R)
Magdalena Sikorska
(M)
Justyna Podlodowska
(J)
Patrick Imesch
(P)
Viola Heinzelmann
(V)
Manuela Rabaglio
(M)
Jon Krell
(J)
John Mcgrane
(J)
Doina Badea
(D)
Rajanee Bhana
(R)
Caroline Chau
(C)
Rebecca Bowen
(R)
Charlie Gourley
(C)
Jenny Forrest
(J)
Ros Glasspool
(R)
Laura Holman
(L)
Sanaz Memarzadeh
(S)
Michael Gold
(M)
David Bender
(D)
Oi Wah Stephanie Yap
(OWS)
James Barter
(J)
Michael Callahan
(M)
Lee-May Chen
(LM)
Tashanna Myers
(T)
Paul Disilvestro
(P)
David O'Malley
(D)
Elena Ratner
(E)
Luis Rojas
(L)
Sharad Ghamande
(S)
Eva Chalas
(E)
Setsuko Chambers
(S)
Corrine Zarwan
(C)
John Chan
(J)
LaToya Perry
(L)
Ying Zhuo
(Y)
Karim ElSahwi
(K)
Walter Gajewski
(W)
Jamie Lesnock
(J)
David Harry Moore
(DH)
Kathleen Yost
(K)
Katrina Wade
(K)
Sharyn Lewin
(S)
James Burke
(J)
Peter Rose
(P)
Theresa Werner
(T)
Melanie Bergman
(M)
Linda Van Le
(L)
Brian Slomovitz
(B)
Amy Brown
(A)
Josh Press
(J)
Patricia Braly
(P)
Sara Keck
(S)
Gerardo Colon-Otero
(G)
Arielle Lee
(A)
Sudarsham Sharma
(S)
Noelle Cloven
(N)
Cheryl Bailey
(C)
Joseph Buscema
(J)
Dana Chase
(D)
Charles Anderson
(C)
Christine Lee
(C)
Antonio Santillan-Gomez
(A)
Diane Provencher
(D)
Amit Oza
(A)
Allan Covens
(A)
Johanne Weberpals
(J)
Susie Lau
(S)
Stephen Welch
(S)
Aalok Kumar
(A)
Deepu Mirchandani
(D)
Vladimir Vladimirov
(V)
Evgeny Gotovkin
(E)
Vladimir Moiseenko
(V)
Sufia Safina
(S)
Denis Yukalchuk
(D)
Vadim Shirinkin
(V)
Anna Buiniakova
(A)
Oleg Gladkov
(O)
Olga Mikheeva
(O)
Natalia Musaeva
(N)
Marina Nechaeva
(M)
Tatiana Semiglazova
(T)
Anna Kryzhanivska
(A)
Hryhorii Adamchuk
(H)
Igor Bondarenko
(I)
Olena Kolesnik
(O)
Oleksii Kolesnik
(O)
Iryna Lytvyn
(I)
Serhii Shevnia
(S)
Iryna Sokur
(I)
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 Massachusetts Medical Society.