Mansoor R Mirza1, B Benigno2, A Dørum3, S Mahner4, P Bessette5, I Bover Barceló6, D Berton-Rigaud7, J A Ledermann8, B J Rimel9, J Herrstedt10, S Lau11, A du Bois12, A Casado Herráez13, E Kalbacher14, J Buscema15, D Lorusso16, I Vergote17, T Levy18, P Wang19, F A de Jong20, D Gupta19, U A Matulonis21. 1. Nordic Society of Gynaecological Oncology Clinical Trial Unit (NSGO-CTU), Rigshospitalet-Copenhagen University Hospital, Copenhagen, Denmark. Electronic address: mansoor@rh.regionh.dk. 2. Northside Hospital, Atlanta, GA, USA. 3. Radiumhospitalet, Oslo University Hospital, NSGO, Oslo, Norway. 4. Department of Obstetrics and Gynecology, University Hospital, LMU Munich, AGO, Munich, Germany. 5. Sherbrooke University, Sherbrooke, QC, Canada. 6. Hospital Son Llàtzer, GEICO, Palma de Mallorca, Spain. 7. Institut de Cancérologie de l'Ouest Centre René Gauducheau, GINECO, Saint-Herblain, France. 8. UCL Cancer Institute, University College London, NCRI, London, UK. 9. Cedars-Sinai Medical Center, West Hollywood, CA, USA. 10. Odense University Hospital, Odense, Denmark; Zealand University Hospital, NSGO, Roskilde, Denmark. 11. McGill University, Montreal, QC, Canada. 12. Kliniken Essen Mitte, AGO, Essen, Germany. 13. Hospital Clínico San Carlos, GEICO, Madrid, Spain. 14. Centre Hospitalier Régional et Universitaire de Besançon, GINECO, Besançon, France. 15. Arizona Oncology Associates, Tucson, AZ, USA. 16. Fondazione Policlinico Universitario a Gemelli IRCCS, Istituto Nazionale dei Tumori, MITO, Milan, Italy. 17. University of Leuven, Leuven Cancer Institute, BGOG, Leuven, Belgium. 18. Wolfson Medical Center, ISGO, Holon, Israel. 19. GlaxoSmithKline, Waltham, MA, USA. 20. GlaxoSmithKline, Zug, Switzerland. 21. Dana-Farber Cancer Institute, Boston, MA, USA.
Abstract
OBJECTIVE:Niraparib 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. METHODS: This 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). RESULTS: Overall, 367 patients receivedniraparib 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. CONCLUSION: These 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 REGISTRATION: ClinicalTrials.gov identifier: NCT01847274.
RCT Entities:
OBJECTIVE:Niraparib 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. METHODS: This 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). RESULTS: Overall, 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. CONCLUSION: These 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 REGISTRATION: ClinicalTrials.gov identifier: NCT01847274.
Authors: Konstantin Weber-Lassalle; Corinna Ernst; Alexander Reuss; Kathrin Möllenhoff; Klaus Baumann; Christian Jackisch; Jan Hauke; Dimo Dietrich; Julika Borde; Tjoung-Won Park-Simon; Lars Hanker; Katharina Prieske; Sandra Schmidt; Nana Weber-Lassalle; Esther Pohl-Rescigno; Stefan Kommoss; Frederik Marmé; Florian Heitz; Julia C Stingl; Rita K Schmutzler; Philipp Harter; Eric Hahnen Journal: J Natl Cancer Inst Date: 2022-04-11 Impact factor: 13.506
Authors: Roni Nitecki; Alexander Melamed; Allison A Gockley; Jessica Floyd; Kate J Krause; Robert L Coleman; Ursula A Matulonis; Sharon H Giordano; Karen H Lu; J Alejandro Rauh-Hain Journal: Gynecol Oncol Date: 2021-03-15 Impact factor: 5.304
Authors: Antonella Padella; Andrea Ghelli Luserna Di Rorà; Giovanni Marconi; Martina Ghetti; Giovanni Martinelli; Giorgia Simonetti Journal: J Hematol Oncol Date: 2022-01-22 Impact factor: 17.388