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: 46.6 vs 48.8 months, HR: 1.01 (0.84-1.23, p=0.8834)
TFST: 18.6 vs 12.0 months, HR: 0.65 (0.52-0.80) (47% data maturity)
5-year PFS rate: 22 vs 12%

HRD+ (incl. BRCA MUT):
PFS: 24.5 (n=247) vs 11.2 months (n=126), HR: 0.51 (0.40-0.66, p<0.001)
OS: 71.9 vs 69.8 months, HR: 0.95 (0.70-1.29)
TFST: NR vs 13.7 months, HR: 0.46 (0.33-0.64)
5-year PFS rate: 35 vs 16%

Exploratory analyses:
BRCA MUT: PFS: 30.1 vs 11.5 months. HR: 0.43 (0.31-0.59)
HRD+ (excl. BRCA MUT): PFS: 19.4 vs 10.4 months, HR: 0.67 (0.45-1.00)
HRD-: PFS: 8.4 vs 5.4 months, HR: 0.67 (0.50-0.89, p=0.0038); TFST: 11.6 vs 7.9 months, HR: 0.64 (0.46-0.90); OS: 36.6 vs 32.2 months, HR: 0.93 (0.69-1.26); 5-year PFS rate: 8 vs 7%
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 (2.3 vs 1.6%)
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, but no OS benefit. In the HRD+ population, patients alive at 5 years were two times as likely to be progression free with niraparib treatment than placebo

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/

Valabrega G et al. Efficacy and safety of niraparib in patients aged 65 years and older with advanced ovarian cancer: Results from the PRIMA/ENGOT-OV26/GOG-3012 trial. Gynecol Oncol (2024) 187:128-138
https://pubmed.ncbi.nlm.nih.gov/38833992/

Kamrava MR et al. Patterns of initial ovarian cancer recurrence on niraparib maintenance monotherapy in patients with no baseline evidence of disease after first-line chemotherapy: An ad hoc subgroup analysis of PRIMA/ENGOT-OV26/GOG-3012. Gynecol Oncol (2024) 189:68-74
https://pubmed.ncbi.nlm.nih.gov/39032397/

Monk BJ et al. Niraparib first-line maintenance therapy in patients with newly diagnosed advanced ovarian cancer: final overall survival results from the PRIMA/ENGOT-OV26/GOG-3012 trial. Ann Oncol (2024) 35(11):981-992
https://pubmed.ncbi.nlm.nih.gov/39284381/

González-Martín A et al. Final overall survival (OS) in patients (pts) with newly diagnosed advanced ovarian cancer (aOC) treated with niraparib (nir) first-line (1L) maintenance: Results from PRIMA/ENGOT-OV26/GOG-3012. Ann Oncol (2024) 35 (2) abstract LBA29
https://www.clearityfoundation.org/wp-content/uploads/2024/11/PRIMA-ESMO-2024-abstract.pdf