• Mansoor R Mirza, B Benigno, A Dørum, S Mahner, P Bessette, I Bover Barceló, D Berton-Rigaud, J A Ledermann, B J Rimel, J Herrstedt, S Lau, A du Bois, A Casado Herráez, E Kalbacher, J Buscema, D Lorusso, I Vergote, T Levy, P Wang, F A de Jong, D Gupta, and U A Matulonis.
• Nordic Society of Gynaecological Oncology Clinical Trial Unit (NSGO-CTU), Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: mansoor@rh.regionh.dk.
• Gynecol. Oncol. 2020 Nov 1; 159 (2): 442-448.

ObjectiveNiraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor approved for use in heavily pretreated patients and as maintenance treatment in patients with newly-diagnosed or recurrent ovarian cancer following a response to platinum-based chemotherapy. We present long-term safety data for niraparib from the ENGOT-OV16/NOVA trial.MethodsThis multicenter, double-blind, randomized, controlled phase III trial evaluated the efficacy and safety of niraparib for the treatment of recurrent ovarian cancer. Patients were randomly assigned 2:1 to receive either once-daily niraparib 300 mg or placebo. Two independent cohorts were enrolled based on germline BRCA mutation status. The primary endpoint was progression-free survival, reported previously. Long-term safety data were from the most recent data cutoff (September 2017).ResultsOverall, 367 patients received niraparib 300 mg once daily. Dose reductions due to TEAEs were highest in month 1 (34%) and declined every month thereafter. Incidence of any-grade and grade ≥ 3 hematologic and symptomatic TEAEs was also highest in month 1 and subsequently declined. Incidence of grade ≥ 3 thrombocytopenia decreased from 28% (month 1) to 9% and 5% (months 2 and 3, respectively), with protocol-directed dose interruptions and/or reductions. Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) were reported in 2 and 6 niraparib-treated patients, respectively, and in 1 placebo patient each. Treatment discontinuations due to TEAEs were <5% in each month and time interval measured.ConclusionThese data demonstrate the importance of appropriate dose reduction according to toxicity criteria and support the safe long-term use of niraparib for maintenance treatment in patients with recurrent ovarian cancer.Trial RegistrationClinicalTrials.gov identifier: NCT01847274.Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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