Niraparib is an oral, highly selective inhibitor of PARP1/2. This is the first randomized phase 3 trial of a PARP inhibitor as maintenance therapy post-platinum chemotherapy in patients (pts) with platinum-sensitive recurrent ovarian cancer.
Two independent cohorts were enrolled based on results of BRACAnalysis® testing: pts with a germline BRCA mutation (gBRCAmut), and pts who lacked these mutations (non-gBRCAmut). Within each cohort, pts were randomized (2:1) to receive niraparib 300 mg or placebo once daily. Three prospectively-defined populations were assessed: 1) the gBRCAmut cohort; 2) those in the non-gBRCAmut cohort whose tumors were retrospectively defined as deficient in homologous recombination (HRD) by the myChoice® HRD test; 3) the overall non-gBRCAmut cohort.
553 pts were enrolled in this international trial. 60% of pts had 2 lines of prior therapy, and 40% of pts had >2 prior lines. 76% of pts had stage IIIc or IV disease. Niraparib prolonged progression-free survival (PFS) as compared to placebo in all three pt populations (Table 1). Secondary endpoints of chemotherapy-free interval (CFI), time to first subsequent treatment (TFST), and PFS 2 also showed statistically significant improvement. Patient-reported outcomes (PRO) were similar for niraparib and placebo. Most common (≥10%) treatment-emergent grade 3/4 adverse events in niraparib-treated pts were thrombocytopenia (28%), anaemia (25%), and neutropenia (11%). There were no deaths during study treatment.
|gBRCAmut n = 203||non-gBRCAmut n = 350||non-gBRCAmut HRDpos n = 162|
|Niraparib n = 138||Placebo n = 65||Niraparib n = 234||Placebo n = 116||Niraparib n = 106||Placebo n = 56|
|PFS Median, Months (95% CI)||21.0 (12.9, NR)||5.5 (3.8, 7.2)||9.3 (7.2, 11.2)||3.9 (3.7, 5.5)||12.9 (8.1, 15.9)||3.8 (3.5, 5.7)|
Niraparib significantly improved PFS for all study populations as well as significantly prolonging CFI, TFST and PFS 2 with a manageable safety profile and without adversely impacting PRO.
Clinical trial identification
Legal entity responsible for the study
B.J. Monk: Consultant for GSK, Merck, Tesaro, Genentech, AZ, Gradalis, Advaxis, Verastem, Cerulean, Amgen, Vermillion, Immunogen, Bayer, NuCana BioMed, Insys Therapeutics, Clovis Oncology, Oxigene, Pfizer – Speaker for Genentech, AZ, Janssen, Myriad Genetics. A. Oza: Consultant for Amgen, Verastem, Clovis Oncology, Immunovaccine. S. Mahner: Consultant for Roche, AZ, MSD, Jansen-Cilag, Tesaro, Medac – Honorarium from Roche/Genentech, AZ, PharmaMar, Medac, Jenapharm, Janssen-Cilag, Teva, GSK – Research support from Roche, AZ, BI, GSK, Janssen-Cilag, Medac, PharaMar, Tesaro, Bayer. A. Redondo: Consultant for Roche, PharaMar – Honorarium from Roche – Speaker for Roche. M. Fabbro: Has received travel support from Roche. J. Ledermann: Consultant for AZ/MedImmune, Clovis Oncology – Research support from AZ. D. Lorusso: Consultant for AZ, PharaMar, Roche Glycart – Speaker for PharmaMar – travel support from PharaMar, Roche Glycart. I.B. Vergote: Consultant & researcher for AZ, Amgen NV, Array Biopharma, Biogen, BI, BMS, Esai, Lilly, Endocye, Genentech, GSK, Janssen-Cilag, Medimmune, MSD, Morphotek, Nektar, Novo Nordisk, Oasmia, PharaMar, Roche, Sanofi, Shering-Plough, Sigma-Tau, among others. J. Berek: Consultant for Prima BioMed, Atara Biotherapeutics – Research support from Tesaro, Quest Diagnostics, Endocyte, Genentech, AZ, Prima BioMed. J. Herrstedt: Consultant for Tesaro. A.V. Tinker: Consultant for AZ – Research support from AZ/MedImmune. A. Dubois: Consultant for AZ, PharaMar, Roche/Genentech, Mundipharma, Pfizer. A. Gonzalez Martin: Consultant for PharaMar, Roche Glycart, - Speaker for AZ, PharaMar, Roche Glycart P. Follana: Has received travel support from AZ and Roche Glycart. B. Benigno: Consultant for Genentech – Speaker for and received honorarium from AZ, Insys Therapeutics – Travel support from AZ. B.J. Rimel: Consultant for AZ – Received Honorarium from Genentech S. Agarwal: Is an employee of Tesaro. U. Matulonis: Consultant for Merck KGaA, AZ, Immunogen, Tesaro, Genentech. All other authors have declared no conflicts of interest.