Niraparib therapy in patients with newly diagnosed advanced ovarian cancer (PRIMA/ENGOT-OV26/GOG-3012 study)

Abstract

Abstract Background Niraparib has shown progression-free survival (PFS) benefit in recurrent OC after platinum-based chemotherapy (CT) in all patients (pts) regardless of BRCA status. This study evaluated the efficacy of niraparib in pts with newly diagnosed advanced OC after completion of first-line (1L) CT regardless of BRCA status. Methods This double-blind, placebo (PBO)-controlled phase III trial evaluated niraparib in pts with newly diagnosed advanced high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube cancer with a complete or partial response (CR or PR) to 1L platinum-based CT. Stratification factors were best response to the 1L CT regimen (CR/PR), receipt of neoadjuvant CT (NACT; yes/no), and homologous recombination deficiency (HRD) status (positive/negative/unknown) per the Myriad myChoice HRD test. Pts received niraparib or PBO once daily. PFS assessed by blinded independent central review was the primary end point, analyzed using a stratified Cox proportional hazards model and hierarchically tested in HRD-positive (HRDpos) pts and then the overall population. Results Of 733 randomized pts (niraparib, 487; PBO, 246), 373 (51%) were HRDpos (niraparib, 247; PBO, 126). Overall, 35% had stage IV disease, 67% received NACT, and 31% had a PR to 1L CT. Niraparib-treated pts in the HRDpos subgroup and overall population had a significant reduction in the risk of disease recurrence or death with a substantial improvement in PFS (Table). All subgroups showed a sustained and durable treatment effect. The most common grade ≥3 adverse events were anemia (31%), thrombocytopenia (29%), and neutropenia (13%). No treatment-related deaths occurred. Table . LBA1 Niraparib mPFS (95% CI) PBO mPFS (95% CI) Hazard Ratio (95% CI) P Value HRDpos subgroup 21.9 (19.3–NE) 10.4 (8.1–12.1) 0.43 (0.31–0.59) P\xa0 Overall population 13.8 (11.5–14.9) 8.2 (7.3–8.5) 0.62 (0.5–0.75) P\xa0 CI, confidence interval; mPFS, median progression-free survival; NE, not estimable. Conclusions Niraparib significantly improved PFS in pts with newly diagnosed advanced OC, including pts at high risk of progressive disease in the HRDpos subgroup and overall population. No new safety signals were identified. Niraparib should be considered as a treatment option for pts with advanced OC after completion of 1L CT. Clinical trial identification NCT02655016. Editorial acknowledgement Writing and editorial support, funded by Tesaro, a GSK Company (Waltham, MA, USA) and coordinated by Ashujit Tadge, PhD of TESARO, was provided by Nicole Renner, PhD of Ashfield Healthcare Communications (Middletown, CT, USA) and Adrienne M. Schreiber, of Tesaro (Waltham, MA, USA). Legal entity responsible for the study Tesaro: A GSK Company. Funding Tesaro: A GSK Company. Disclosure A. Gonzalez Martin: Research grant / Funding (institution): Roche; Advisory / Consultancy: AstraZeneca Tesaro; Advisory / Consultancy: Pharmamar; Advisory / Consultancy: Tesaro, Inc.. B. Pothuri: Advisory / Consultancy: Tesaro, Inc.; Advisory / Consultancy: Clovis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Intuitive. I.B. Vergote: Advisory / Consultancy: GCI Health, Oncoinvent AS, Roche NV; Research grant / Funding (institution): Roche; Advisory / Consultancy: Genmab A/S, Advaxid Inc, Morphotek Inc; Advisory / Consultancy: F. Hoffmann-La Roche Ltd, Cerulean Pharma Inc, Novocure GMBH; Advisory / Consultancy: AstraZeneca, Mateon Therapeutics Inc; Advisory / Consultancy: Immunogen, Eli Lilly; Advisory / Consultancy, Research grant / Funding (self): Amgen; Advisory / Consultancy: Theradex Europe Limited, Pfizer, Debiopharma International SA; Advisory / Consultancy: Vifor Pharma Belgie NV, Novartis, MSD Belgium BVBA; Advisory / Consultancy: Oxigene, Janssen-Dilag, Nektar Therapeutics, Bayer; Travel / Accommodation / Expenses: Tesaro, Theradex, Elsevier. R.D. Christensen: Advisory / Consultancy: Tesaro: A GSK Company. W. Graybill: Advisory / Consultancy, Speaker Bureau / Expert testimony: Tesaro, Inc.. M.R. Mirza: Advisory / Consultancy: Clovis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro, Inc.. D. Lorusso: Honoraria (self), Personal fees: AstraZeneca; Honoraria (self), Personal fees: Clovis Oncology; Honoraria (self), Personal fees: Genmab; Honoraria (self), Personal fees: Immunogen; Honoraria (self), Personal fees: Pharma Mar S.A; Honoraria (self), Personal fees: Amgen; Honoraria (self), Personal fees: Merck; Research grant / Funding (institution): Pharma Mar S.A; Research grant / Funding (institution): Merck. G. Freyer: Honoraria (self), Personal fees: Tesaro: A GSK Company; Honoraria (self), Personal fees: Clovis Oncology; Honoraria (self), Personal fees: Bristol-Myers Squibb ; Honoraria (self), Personal fees: MSD; Honoraria (self), Personal fees: Pfizer Inc. ; Honoraria (self), Personal fees: Novartis; Honoraria (self), Personal fees: Eli Lilly ; Honoraria (self), Personal fees: Biogara S.A.S; Honoraria (self), Research grant / Funding (institution), Personal fees: AstraZeneca; Honoraria (self), Research grant / Funding (institution), Personal fees: Roche Holding AG ; Honoraria (self), Research grant / Funding (institution), Personal fees: Mylan. F. Backes: Honoraria (self), Advisory / Consultancy, Personal fees: Clovis Oncology ; Honoraria (self), Advisory / Consultancy, Personal fees: Merck ; Honoraria (self), Advisory / Consultancy, Personal fees: Eisai ; Honoraria (self), Personal fees: Tesaro; Honoraria (self), Personal fees: Agenus; Honoraria (self), Personal fees: CEC Oncology; Research grant / Funding (institution): Immunogen. A. Redondo: Advisory / Consultancy, Research grant / Funding (institution): Pharmamar; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Research grant / Funding (institution): Eisai. R.G. Moore: Research grant / Funding (institution): Angle PLC; Advisory / Consultancy: Fugirebio Diagnostics Inc. R.E. O’Cearbhaill: Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: GlaxoSmithKline. Y. Li: Shareholder / Stockholder / Stock options, Full / Part-time employment: Tesaro, Inc.. D. Gupta: Shareholder / Stockholder / Stock options, Full / Part-time employment: Tesaro, Inc.. B.J. Monk: Honoraria (self), Advisory / Consultancy: AbbVie, Advaxis; Honoraria (self), Advisory / Consultancy: Agenus, Amgen; Honoraria (self), Advisory / Consultancy: AstraZeneca, Biodesix; Honoraria (self), Advisory / Consultancy: Clovis, Conjupro; Honoraria (self), Advisory / Consultancy: Genmab, Gradalis; Honoraria (self), Advisory / Consultancy: ImmunoGen, Immunomedics; Honoraria (self), Advisory / Consultancy: Incyte, Janssen; Honoraria (self), Advisory / Consultancy: Mateon, Merck; Honoraria (self), Advisory / Consultancy: Myriad, Perthera; Honoraria (self), Advisory / Consultancy: Pfizer, Precision; Honoraria (self), Advisory / Consultancy: Puma, Roche; Honoraria (self), Advisory / Consultancy: Samumed, Takeda; Honoraria (self), Advisory / Consultancy: Tesaro, VB. All other authors have declared no conflicts of interest.