Abstract 3367
Background
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.
Methods
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.
Results
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.
Progression-free Survival
| 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) |
| p value | ConclusionsNiraparib 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 identificationNCT01847274 Legal entity responsible for the studyTesaro Inc. FundingTesaro, Inc. DisclosureB.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. Resources from the same sessionIpilimumab (IPI) vs placebo (PBO) after complete resection of stage III melanoma: final overall survival results from the EORTC 18071 randomized, double-blind, phase 3 trialPresenter: Alexander Eggermont Session: Presidential Symposium 1 Resources: Abstract Slides Invited discussant LBA3Presenter: Sandro Pignata Session: Presidential Symposium 1 Resources: Slides Invited discussant LBA2Presenter: Olivier Michielin Session: Presidential Symposium 1 Resources: Slides Invited discussant LBA1Presenter: Stephen Johnston Session: Presidential Symposium 1 Resources: Slides First-line ribociclib + letrozole for postmenopausal women with hormone receptor-positive (HR+), HER2-negative (HER2–), advanced breast cancer (ABC)Presenter: Gabriel Hortobagyi Session: Presidential Symposium 1 Resources: Abstract Slides This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used. For more detailed information on the cookies we use, please check our Privacy Policy.
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