Niraparib

證據等級: L5

預測適應症: 10 個

Niraparib: From Ovarian Cancer Maintenance Therapy to Cystic Neoplasm

One-Sentence Summary

Niraparib is a PARP inhibitor established as maintenance therapy for platinum-sensitive recurrent ovarian, fallopian tube, and primary peritoneal cancer. Among 10 TxGNN-predicted indications for this drug, Cystic Neoplasm (rank 2) is the only candidate with substantive supporting evidence — 3 clinical trials and 9 publications — while the remaining 9 candidates (including the top-ranked “epiglottis neoplasm”) have no clinical trial or literature support at all.

Quick Overview

Item	Content
Original Indication	Not available from Australian regulatory data (niraparib is not TGA-registered); internationally approved as maintenance treatment for platinum-sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer (per clinical trial evidence in this pack, not TGA PI)
Predicted New Indication	Cystic Neoplasm
TxGNN Prediction Score	99.99% (0.999876)
Evidence Level	L2
Australia Market Status	Not marketed (0 ARTG entries)
Number of ARTG Entries	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Structured mechanism-of-action data for niraparib is flagged as a data gap in this evidence pack. However, the clinical trial and literature evidence independently collected confirms niraparib is a poly(ADP-ribose) polymerase (PARP) inhibitor that exploits synthetic lethality in tumours with homologous recombination deficiency (HRD), and is already an FDA-recognised maintenance therapy for recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer.

“Cystic Neoplasm” is a broad disease label, but the actual evidence retrieved for this candidate is concentrated on high-grade serous ovarian carcinoma and uterine/endometrial serous carcinoma — both cystic, adnexal tumour types that are molecularly closely related to niraparib’s established indication (shared chromosomal instability, comparable HRD prevalence, and an overlapping treatment paradigm with HGSOC). This makes the prediction a mechanistically coherent extension of niraparib’s known pharmacology rather than a speculative label match.

By contrast, most of the other TxGNN-ranked candidates for this drug (see note near the end of this report) have no clinical or literature evidence at all, despite similar TxGNN scores — underscoring that TxGNN score alone should not be used to prioritise candidates without evidence triangulation.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrolment	Key Findings
NCT04716686	Phase 2	Recruiting	83	Multi-centre, open-label study of niraparib monotherapy as maintenance/recurrent treatment for endometrial serous carcinoma, based on its molecular similarity to high-grade serous ovarian carcinoma (Grade A relevance)
NCT04159155	Phase 2/3	Terminated	11	Canadian umbrella trial assessing front-line and maintenance treatment (including niraparib-relevant arms) in serous/p53-mutant endometrial cancer; terminated early with very small enrolment (Grade B relevance)
NCT05289648	Early Phase 1	Withdrawn	0	Preoperative niraparib in high-grade endometrial cancer; withdrawn before enrolment, no data generated (Grade C relevance)

Literature Evidence

PMID	Year	Type	Journal	Key Findings
40473279	2025	Cohort (protocol)	BMJ Open	Phase 2 study protocol for niraparib maintenance in stage III/IV chemo-naïve or platinum-sensitive recurrent uterine serous carcinoma, a poor-prognosis endometrial cancer subtype
34321239	2021	Cohort	Cancer Research	Loss of RAD51C promoter methylation drives PARP inhibitor resistance in HGSOC PDX models, informing biomarker-based patient selection for niraparib
41323499	2025	Review	Pathology Oncology Research	Comprehensive genomic profiling for homologous recombination deficiency to guide PARP inhibitor therapy decisions in ovarian cancer
41214101	2025	Review	Scientific Reports	Claudin-4 regulates genome stability and immune evasion in HGSOC, relevant to PARP inhibitor and immune-based combination strategies
41520277	2026	Review	Cancer Biology & Therapy	Reviews carboplatin + PARP inhibitor combinations (olaparib approved for BRCA1/2-mutated HGSC; niraparib approved for platinum-sensitive recurrent disease) using spheroid/organoid models
31851805	2019	Review	New England Journal of Medicine	Personalised medicine approaches for primary treatment of serous ovarian cancer
40702505	2025	Review	Journal of Ovarian Research	Identifies cancer stem cell-based molecular subtypes and a prognostic model in HGSOC
41465250	2025	Review	International Journal of Molecular Sciences	Proteomic profiling of poly-pharmacological effects of PARP inhibitors (olaparib, niraparib, rucaparib) in HGSOC cells, relevant to adverse effect mechanisms
31466953	2019	Case Report	BMJ Case Reports	Case of niraparib maintenance therapy in an ovarian cancer patient with brain metastases

Australia Market Information

Niraparib currently has no ARTG entries — it is not registered or marketed in Australia based on the data available in this evidence pack.

Cytotoxicity

Niraparib is an antineoplastic agent (PARP inhibitor), so this section applies.

Item	Content
Cytotoxicity Classification	Targeted therapy (PARP inhibitor), not conventional cytotoxic chemotherapy
Myelosuppression Risk	PARP inhibitors as a class are associated with haematological toxicity (anaemia, thrombocytopenia, neutropenia); drug-specific severity data was not available in this evidence pack — please refer to the Product Information (PI) warnings and precautions
Emetogenicity Classification	Please refer to the Product Information (PI) warnings and precautions
Monitoring Items	FBC with differential; liver and renal function
Handling Protection	Please refer to the Product Information (PI) warnings and precautions

Safety Considerations

Please refer to the TGA-approved Product Information (PI) for safety information.

Other TxGNN-Predicted Candidates (Same Drug)

For context, this evidence pack scored 10 candidate indications for niraparib with near-identical TxGNN scores (~99.99%). Only two others returned any evidence at all:

Candidate	Evidence Level	Decision Stage	Recommendation
Pre-malignant neoplasm	L3	S1	Research Question — trials found are niraparib-specific but tested in confirmed malignancies, not pre-malignant populations
Epiglottis neoplasm, benign neoplasms of tongue/hypopharynx/floor of mouth, cervical neuroblastoma, testis/paratestis tumour, inner ear neoplasm, schwannoma of jugular foramen (7 candidates)	L5	S0	Hold — no clinical trials or literature identified

These illustrate that TxGNN score alone does not indicate evidentiary strength; only Cystic Neoplasm cleared to S2 evidence maturity.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: One actively recruiting Phase 2 trial (NCT04716686, n=83) directly tests niraparib monotherapy in endometrial serous carcinoma — a cystic/serous tumour mechanistically aligned with niraparib’s established HRD-targeting activity — supported by 9 publications on the underlying biology. Evidence is real but not yet definitive (no completed Phase 3 data specific to this indication).

To proceed, the following is needed:

TFDA/TGA product information and formal safety data for niraparib (currently a blocking data gap)
Structured mechanism-of-action documentation from DrugBank
Confirmation of the intended clinical population (Cystic Neoplasm as a label is broader than the serous ovarian/endometrial carcinoma population actually studied)
Outcome data from NCT04716686 upon completion (currently recruiting, due 2026-12-31)
Regulatory pathway assessment given niraparib is not currently registered in Australia
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.