title: Niraparib for the treatment of ovarian cancer.
abstract: Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors are being developed in maintenance and recurrence treatment settings in ovarian cancer. They inhibit single-stranded DNA repair, inducing synthetic lethality in cells with underlying homologous recombination deficiency (HRD). Marked responses are seen in ovarian cancers with breast cancer gene 1 (BRCA1) or 2 (BRCA2) mutation, although up to 50% of high-grade serous ovarian cancers (HGSOC) have HRD may also benefit. Areas covered: This review focuses on niraparib (oral PARP I and II inhibitor), its clinical testing in ovarian cancer, including the Myriad MyChoice HRD test as a potential companion diagnostic. Future directions plus ongoing trials, including novel combinations are highlighted. Expert opinion: There is now level 1 evidence of efficacy from the first randomized placebo-controlled phase III trial using niraparib maintenance in women with platinum-sensitive recurrent HGSOC with complete or partial response post platinum-based chemotherapy. Niraparib improved progression free survival over placebo in all groups of women. The benefit was greatest in patients with germline BRCA1/2 mutation, followed by HRD positive tumors; however, absence of either does not exclude the possibility of benefit from niraparib maintenance. Additional studies are underway with niraparib in the first line maintenance, and 4th/5thline recurrence treatment settings.
authors.affiliation: a Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre , University of Toronto , Toronto , Canada.
authors.forename: Yada
authors.initials: Y
authors.lastname: Kanjanapan
authors.affiliation: a Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre , University of Toronto , Toronto , Canada.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lheureux
authors.affiliation: a Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre , University of Toronto , Toronto , Canada.
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007191:Indazoles / Q000627:therapeutic use*; D009154:Mutation; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010880:Piperidines / Q000627:therapeutic use*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D007191:Indazoles; D010880:Piperidines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C545685:niraparib
keywords: BRCA1/2 mutation; Niraparib; homologous recombination deficiency; maintenance; ovarian cancer