Niraparib — Drug Monograph
Brand names: Zejula
Drug class: PARP Inhibitor
Mechanism of Action
Selective inhibitor of poly(ADP-ribose) polymerase 1 and 2 (PARP1/2). Like olaparib, niraparib traps PARP at single-strand DNA breaks, converting them to lethal double-strand breaks during replication — a mechanism of synthetic lethality in BRCA-deficient tumors. Critically, niraparib's clinical benefit extends beyond BRCA-mutated cancers: patients with homologous recombination deficiency (HRD), defined by genomic instability scores (myChoice CDx assay) or BRCA mutation, derive meaningful benefit. This broader HRD-based patient selection — compared to olaparib's tighter BRCA focus in some…
FDA Indications
- Advanced ovarian, fallopian tube, or primary peritoneal cancer — first-line maintenance after complete or partial response to platinum-based chemotherapy (PRIMA trial — all-comers, regardless of BRCA/HRD status; greatest benefit in HRD-positive subgroup)
- Advanced ovarian cancer — maintenance treatment after complete or partial response to platinum-based chemotherapy in recurrent disease (NOVA trial)
- Advanced ovarian, fallopian tube, or primary peritoneal cancer — third-line or later treatment of BRCA-mutated tumors
Common Side Effects
- Thrombocytopenia (most common dose-limiting toxicity; more frequent/severe than with olaparib)
- Anemia
- Neutropenia
- Nausea
- Fatigue
- Constipation
- Vomiting
- Hypertension (class-distinct; related to dopamine reuptake inhibition)
- Palpitations / tachycardia
- Headache
- Insomnia
Clinical Pearl
Niraparib is the only PARP inhibitor approved as first-line ovarian cancer maintenance regardless of BRCA or HRD status (PRIMA trial) — a major clinical advantage when biomarker testing is pending or unavailable. However, the absolute PFS benefit is markedly greater in HRD-positive patients (BRCA-mutated or genomic instability-positive): HRD-positive subgroup HR 0.43 vs. HRD-negative subgroup HR 0.68. Thrombocytopenia management is critical — use the individualized 200/300 mg starting dose…
Related Therapies & Mechanisms
- Olaparib (Lynparza) — PARP Inhibitor · Ovarian
- Rucaparib (Rubraca) — PARP Inhibitor · Ovarian
- Talazoparib (Talzenna) — PARP Inhibitor
- Avutometinib/Defactinib (Avmapki Fakzynja Co-Pack) — Ovarian