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

Trial ID # NCT02655016; PRIMA
Phase III
Drug Class DNA Damage Repair Pathway Inhibitors: PARP
Drug Name Niraparib
Alternate Drug Names MK4827, Zejula
Drugs in Trial Niraparib
Eligible Participant

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

Patients Enrolled

733

Therapy Setting

Maintenance

Study Design

Double Blind, Randomized

Endpoints

PFS, OS, TFST, evaluated per RECIST

Biomarkers

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

Efficacy

Nir maint vs Placebo:

All patients:
PFS: 13.8 (n=487) vs 8.2 months (n=246), HR: 0.62 (0.50-0.76, 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: 21.9 (n=247) vs 10.4 months (n=126), HR: 0.43 (0.31-0.59, 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: 0.50 (0.31-0.83)
HRD-: PFS: 8.1 vs 5.4 months, HR: 0.68 (0.49-0.94); 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)

Clinically Significant Adverse Events

Nir maint vs Placebo:
Serious AE: 1 MDS in Nir maint arm
Grade 3-4 AE: any (31.0 vs 1.6%), thrombocytopenia (28.7 vs 0.4%), decreased platelets (13.0 vs 0%), neutropenia (12.8 vs 1.2%)

Conclusion

Considerably improved PFS for all patients that received niraparib maintenance treatment

Reference

González-Martin A et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N Engl J Med (2019) Sep 28
https://www.ncbi.nlm.nih.gov/pubmed/31562799

Han SN et al. Time to first subsequent therapy (TFST) and progression-free survival 2 (PFS2) from the phase 3 randomized, double-blind PRIMA/ENGOT-OV26/GOG-3012 study in patients with newly diagnosed ovarian cancer. SGO (2020) abstract 32
https://sgo.confex.com/sgo/2020/meetingapp.cgi/Paper/16306