Niraparib (Zejula®) is a selective inhibitor of PARP 1/2 approved for maintenance treatment of recurrent ovarian cancer (OC) pts who are in complete or partial response to platinum therapy (plat), regardless of BRCA or HRD status, based on the significantly improved progression-free survival (PFS) for niraparib-treated pts in the pivotal phase 3 ENGOT-OV16/NOVA trial. In NOVA, dose adjustments due to adverse events (AEs) occurred in 69% of pts. Dose adjustments tended to occur early, with most pts reaching their individualized dose within 3 months. A retrospective analysis of NOVA showed that pts with body wt < 77 kg or blplt count <150K/µL were more likely to be dose reduced due to hematologic AEs; efficacy was not compromised in those pts. The PRIMA study evaluates niraparib vs placebo as maintenance therapy in high-risk stage III or IV OC in response to frontline plat therapy. Regular and independent safety data reviews have not identified safety issues in PRIMA. However, the trial was amended to prospectively evaluate the safety and efficacy of a new dosing paradigm.
Plat responsive pts were initially randomized 2:1 to start at niraparib 300 mg qd or placebo. The primary endpoint is PFS. The protocol was amended to require starting dose of 200 mg qd in pts with baseline wt < 77kg or blplt count <150K/µL and 300 mg in all other pts. The trial remains blinded for efficacy and safety.
630 pts are currently enrolled, and 159 pts were dosed based on wt and blplt count. Blinded data were pooled from niraparib and placebo. There were no major differences in key pt demographics or disease characteristics. Key safety data are presented in the table. Data for ≥60 days, ≥90 days, and safety in the overall population will be presented.Table: 941PD
Patients with ≥30 days safety data from blinded pooled niraparib and placebo arms
|Any TEAE||437 (93.8)||80 (74.8)|
|Any related TEAE||385 (82.6)||70 (65.4)|
|Any ≥grade 3 TEAE||227 (48.7)||19 (17.8)|
|Any serious AE||96 (20.6)||8 (7.5)|
|Any grade thrombocytopenia||217 (46.6)||24 (22.4)|
|≥Grade 3 thrombocytopenia||143 (30.7)||6 (5.6)|
|Any grade anemia||191 (41.0)||12 (11.2)|
|≥Grade 3 anemia||77 (16.5)||3 (2.8)|
|TEAE leading to end of treatment||26 (5.6)||2 (1.9)|
These interim safety data suggest that niraparib tolerability is improved when dosing is based upon wt and blplt count.
Clinical trial identification
Legal entity responsible for the study
Writing and editorial support, funded by Tesaro, Inc. (Waltham, MA, USA) and coordinated by Thomas Giove, PhD of Tesaro, Inc., was provided by Nicole Renner, PhD and Dena McWain of Ashfield Healthcare Communications (Middletown, CT, USA).
A. Gonzalez: Grants: Roche; Personal fees: AstraZeneca, PharmaMar, Tesaro, M.R. Mirza: Personal fees: Clovis Oncology, AstraZeneca, Tesaro, I. Vergote: Consulting: GCI Health, Oncoinvent AS, Roche, Genmab, Advaxis, Morphotek, F Hoffman-La Roche, Novocure GMBH, AstraZeneca, Mateon Therapeutics, Immunogen, Eli Lilly Benelux, Amgen, Theradex EU, Pfizer, Debiopharma International, Vifor Pharma Belgie, Novartis, MSD Belgium, Oxigene, Janssen, Nektar Therapeutics, Bayer; Grants: Amgen, Roche; Travel expenses: Tesaro, Theradex, Elsevier, Y. Li, S. Hazard, R. Clark: Employment and stock and other ownership interests: Tesaro Inc, W. Graybill: Consulting or Advisory role: Tesaro, B. Pothuri: Research funding: Tesaro, Caris Life Sciences, Celgene, Clovis Oncology, B.J. Monk: Consulting/Advisory: GSK, Merck, Tesaro, Roche/GNE, AstraZeneca, Gradalis, Advaxis, Verastem, Cerulean, Amgen, Vermillion, Immunogen, Bayer, NuCana BioMed, Insys Therapeutics, Clovis Onc, Oxigene, Pfizer; Speakers bureau: Roche/GNE, AstraZeneca, Janssen, Myriad Genetics.