A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy

Stage III, inoperable or w/ residual tumor after debulking surgery, stage IV, and patients after neoadjuvant therapy, with CR or PR after first-line therapy

733

Maintenance

Double Blind, Randomized

PFS, OS, TFST, evaluated per RECIST

HRD status (myChoice HRD test, Myriad Genetics); Exploratory: BRCA status, HRD status, CR/PR after chemo, neoadjuvant treatment

Nir maint vs Placebo:

All patients:
PFS: 13.8 (n=487) vs 8.2 months (n=246), HR: 0.66 (0.56-0.79, p<0.001)
OS: probability of survival at 24 months: 84 vs 77%, HR: 0.70 (0.44-1.11)
TFST: 18.6 vs 12.0 months, HR: 0.65 (0.52-0.80) (47% data maturity)

HRD+ (incl. BRCA MUT):
PFS: 24.5 (n=247) vs 11.2 months (n=126), HR: 0.52 (0.40-0.68, p<0.001)
OS: probability of survival at 24 months: 91 vs 85%, HR: 0.61 (0.27-1.39)
TFST: NR vs 13.7 months, HR: 0.46 (0.33-0.64)

Exploratory analyses:
BRCA MUT: PFS: 22.1 vs 10.9 months. HR: 0.40 (0.27-0.62)
HRD+ (excl. BRCA MUT): PFS: 19.6 vs 8.2 months, HR: 0.66 (0.41-1.00)
HRD-: PFS: 8.4 vs 5.4 months, HR: 0.65 (0.49-0.87, p=0.0038); TFST: 11.6 vs 7.9 months, HR: 0.64 (0.46-0.90)
CR after chemotherapy: PFS: 16.4 vs 9.5 months, HR: 0.60 (0.46-0.77)
PR after chemotherapy: PFS: 8.3 vs 5.6 months, HR: 0.60 (0.43-0.85)
w/ neo-adjuvant treatment: 13.9 vs 8.2 month, HR: 0.59 (0.46-0.76)
w/ Primary Debulking Surgery (PDS): 13.7 vs 8.2 months, HR: 0.67 (0.47-0.96)
w/ Interval Debulking Surgery (IDS): 14.2 vs 8.2 months, HR: 0.57 (0.44-0.73)
w/ PDS and Visual Residual Disease (VRD, R1/R2): 11.8 vs 7.8 months, HR: 0.58 (0.39-0.86)
w/ IDS and VRD, R1/R2: 11.1 vs 5.6 months, HR: 0.41 (0.27-0.62)
w/ IDS and No Visual Residual Disease (NVRD, R0): 18.2 vs 10.9 months, HR: 0.65 (0.46-0.91)

Nir maint vs Placebo:
Serious AE: MDS/AML (1.2 vs 1.2%)
Grade 3-4 AE: any (31.0 vs 1.6%), thrombocytopenia (40 vs 0.4%), anemia (32 vs 0%), neutropenia (21 vs 1.2%), decreased platelets (13.0 vs 0%)

Considerably improved PFS for all patients that received niraparib maintenance treatment

González-Martin A et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med (2019) 381(25):2391-2402 
https://www.ncbi.nlm.nih.gov/pubmed/31562799

O'Cearbhaill et al. Efficacy of niraparib by time of surgery and postoperative residual disease status: A post hoc analysis of patients in the PRIMA/ENGOT-OV26/GOG-3012 study. Gynecol Oncol (2022) 166(1):36-43
https://pubmed.ncbi.nlm.nih.gov/35550709/

Gonzalez-Martin A et al. Progression-free survival and safety at 3.5 years of follow-up: results from the randomised phase 3 PRIMA/ENGOT-OV26/GOG-3012 trial of niraparib maintenance treatment in patients with newly diagnosed ovarian cancer. Eur J Cancer (2023) 189:112908
https://pubmed.ncbi.nlm.nih.gov/37263896/