Niraparib †Rx
Rx PARP i: Catalytic ↓ + trapping ↑ → HRD lethality; phase III PFS gains in ovarian/breast/prostate/endometrial.
Forms: Oral capsules (100 mg, 200 mg, 300 mg) · Tablets (weight/platelet-adjusted dosing)
Key Takeaway
Oral PARP1/2 inhibitor with clinically proven maintenance and treatment benefits in HRD/BRCA-altered tumors—most robust in ovarian cancer—by blocking PARP repair and trapping PARP on DNA to exploit synthetic lethality.
Evidence at a glance
FDA/EMA-approved for ovarian maintenance (PRIMA, NORA); phase III in prostate (MAGNITUDE); meta-PFS HR 0.45 in HRD+; real-world PSA responses in mCRPC; ongoing in endometrial/breast.
How it may work
Niraparib inhibits PARP catalytic activity and traps PARP-DNA complexes, stalling replication forks and converting single-strand lesions into double-strand breaks. HRD/BRCA-deficient cells cannot repair these DSBs by homologous recombination → apoptosis. Phase III trials show significant PFS gains in ovarian cancer (including all-comer maintenance with strongest effect in HRD-positive subgroups). Combination strategies (e.g., with bevacizumab) and expansion to other HRR-deficient tumors are supported by growing evidence.
Targets & pathways
Curated mechanistic targets reported for this agent — how it may act on cells, not proof of a clinical effect.
- PARP↓Catalytic inhibition of PARP1/2
- PARP Trapping↑DNA complex stabilization → fork collapse
- HRD Synthetic Lethality↑Selective DSB accumulation in repair-deficient cells
- Replication ForkStallConversion SSBs to DSBs
- Apoptosis↑HRD-contextual cell death
Often studied / combined with
Combinations reported in the literature, not a protocol or a recommendation.
- Bevacizumab: PFS HR 0.43 in ovarian PAOLA-1 combo.
- Pembrolizumab: ORR 30% in HRD endometrial phase II.
- Curcumin: Preclinical PARP/ROS synergy in ovarian models.
- Resveratrol: Enhanced HRD kill in breast cancer lines.
Overlapping mechanisms
- PARP: Cross-resistance with olaparib/talazoparib; switch class if progression.
- HRD Lethality: Redundant in BRCA+; monitor for MDS/AML with sequential use.
Safety & interactions
Severity and how well-established each signal is are shown separately. Verify everything with your oncologist or pharmacist — absence here does not mean safe.
- CYP1A2 inhibitorsMonitorLowTheoreticalModest exposure increase (e.g., fluvoxamine).
- P-gp substratesMonitorLowTheoreticalPotential competition (e.g., digoxin).
- BevacizumabSynergizeLowTheoreticalComplementary PFS extension in ovarian.
Timing
- QD: Once daily, same time for steady-state.
- Continuous: No breaks unless toxicity.
References
- PMC9973409: Niraparib in ovarian cancer review
- PMC10529072: PARP trapping mechanisms
- DOI 10.1177/15347354231198074: HRD synthetic lethality
- NEJM 2017: PRIMA trial ovarian maintenance
- JCO 2023: Combinations with bevacizumab
- PMC10221542: Natural synergies in HRD models
Research
No published studies for Niraparib †Rx yet
New studies appear here once they’ve been reviewed. Browse all studies.
Dose: as studied, not a recommendation
Ranges seen in adjunct / practice use: 200–300 mg/day (po) QD continuous; individualized (e.g., 200 mg if platelets <150k), Maintenance 300 mg QD; reduce to 200 mg for toxicity; no food effect but consistent timing..
Clinical trials studying Niraparib †Rx
1 ongoing · 0 completed · tracked from ClinicalTrials.gov. Recruiting is not the same as proven, and completed is not the same as positive — read the results. Not a recommendation.