Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer
- Study type
- Clinical trial
- Study name
- PRIMA (ENGOT-OV26/GOG-3012)
- Phase
- Phase 3
- Design
- Randomised, double-blind, placebo-controlled trial (2:1 ratio)
- Sample size
- 733 patients (373 with homologous recombination deficiency)
- Source
- N Engl J Med · 2019
- Trial registration
- NCT02655016
In plain words
Niraparib is a tablet taken daily for up to three years after chemotherapy ends. In this study, the drug lengthened the time until the disease came back in all patients, and especially in tumours with a DNA repair defect (HRD-positive). However, at the final follow-up of about 6 years, overall survival was no different from placebo; this point should be discussed with your doctor when deciding, especially for HRD-negative tumours.
Key results
Treatment arms and regimens
Niraparib orally once daily. At the start of the study, a fixed dose of 300 mg for all (475 patients); from November 2017, after a protocol amendment, an individualised starting dose: 200 mg for patients with baseline weight below 77 kg or platelets below 150,000 per microlitre, and 300 mg for weight 77 kg or more and platelets 150,000 or more (258 patients). Planned treatment duration 3 years (or until disease progression or unacceptable toxicity).
Placebo once daily on the same schedule.
Source of the regimen details: NEJM 2019 abstract (once daily) and full text of the final analysis, Ann Oncol 2024, in PMC (PMC11934258): fixed dose 300 mg and individualised starting dose 200/300 mg, planned duration 3 years
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with newly diagnosed advanced ovarian cancer at high risk of recurrence who had responded to first-line platinum-based chemotherapy, regardless of BRCA or HRD status.
Endpoints
Primary outcome: progression-free survival, tested hierarchically in patients with homologous recombination deficiency (HRD) and then in the overall population. Secondary: overall survival (concurrent interim analysis; final analysis Ann Oncol 2024).
Safety and side effects
The most common grade 3 or higher adverse events were anaemia (31.0%), thrombocytopenia (28.7%) and neutropenia (12.8%); there were no treatment-related deaths. An individualised starting dose (based on weight and platelet count) reduced haematological toxicity. In the final analysis, the incidence of myelodysplastic syndrome/acute myeloid leukaemia was 2.3% with niraparib and 1.6% with placebo.
Clinical significance and place in guidelines
The FDA approved niraparib in April 2020 for first-line maintenance regardless of biomarker status. The final overall survival analysis (Monk et al, Ann Oncol 2024) showed no difference in overall survival, which may be partly due to PARP inhibitor use after progression in the placebo group (37.8% in the overall population). The ESMO guideline (Pan-Asian version 2025) lists 3 years of niraparib for BRCA-mutated or HRD-positive tumours [I, A] and as an option to consider in HRD-negative tumours [I, B].
Limitations
No overall survival improvement in the final analysis; change of starting dose midway through the study; high-risk population (most patients had residual disease or neoadjuvant chemotherapy), which limits generalisation to lower-risk patients.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.