Niraparib
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Niraparib: Epiglottis neoplasm
One-Sentence Summary
Niraparib is a PARP inhibitor originally used for epithelial ovarian and primary peritoneal cancers. The TxGNN model predicts it may be effective for Cystic Neoplasm, a broad label. The supporting evidence is 3 clinical trials (1 recruiting Phase 2, 1 terminated, 1 withdrawn) and 10 publications, most of which are preclinical or biomarker studies focused on serous gynaecological carcinomas.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Epiglottis neoplasm |
| TxGNN Prediction Score | 0.9999 |
| Evidence Level | L5 (as scored in the data; see note below) |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Note on evidence level: The only Phase 2/3 trial (NCT04159155) was terminated after 11 participants, and the remaining evidence consists of a recruiting Phase 2 trial without results, preclinical work and a case report. On a strict reading of the evidence rules, no completed RCT supports this indication, so the evidence is weak and closer to L4 than to a true L2.
Why is This Prediction Reasonable?
Detailed mechanism of action data are not available in the data compiled for this report. Based on general knowledge, niraparib is a PARP inhibitor. PARP inhibitors exploit synthetic lethality in tumours with homologous recombination deficiency (HRD), such as BRCA-mutated or HRD-positive high-grade serous carcinomas.
Ovarian and primary peritoneal serous carcinomas are often HRD-positive, which is the basis of niraparib’s established use. The trials and publications retrieved cluster on closely related serous gynaecological cancers: endometrial/uterine serous carcinoma and high-grade serous ovarian carcinoma. These share molecular features with the original indications, including chromosomal instability and frequent HRD. This makes a mechanistic extension plausible.
However, “cystic neoplasm” is a broad and heterogeneous label. The evidence applies specifically to serous gynaecological carcinomas, not to cystic neoplasms in general, so the link is indirect.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT04716686 | Phase 2 | Recruiting | 83 | Niraparib monotherapy as maintenance and recurrent treatment in endometrial serous carcinoma. The most direct evidence, but no results are available. |
| NCT04159155 | Phase 2/3 | Terminated | 11 | Multi-arm randomised trial of front-line and maintenance treatment in serous or p53-mutant endometrial cancer. Terminated early; unlikely to give interpretable efficacy data. |
| NCT05289648 | Early Phase 1 | Withdrawn | 0 | Preoperative niraparib in high-grade endometrial cancer. Withdrawn before enrolment; provides no evidence. |
No ANZCTR trial identifiers were found in the data compiled for this report.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 40473279 | 2025 | Clinical trial protocol | BMJ Open | Phase 2 protocol for niraparib maintenance in stage III/IV or recurrent uterine serous carcinoma. |
| 31466953 | 2019 | Case report | BMJ Case Reports | Niraparib maintenance in a patient with ovarian cancer and brain metastases. |
| 41323499 | 2025 | Cohort/biomarker | Pathol Oncol Res | Comprehensive genomic profiling for HRD to guide PARP inhibitor recommendations in ovarian cancer. |
| 42442041 | 2026 | Real-world cohort | Gynecol Oncol | Real-world HRD testing in BRCA1/2 wild-type high-grade serous carcinoma; MYC amplification explored as a surrogate marker. |
| 42157333 | 2026 | Cohort/predictive model | Clin Epigenetics | HRR gene promoter methylation nomogram to predict PARP inhibitor efficacy and progression-free survival in HGSOC. |
| 41520277 | 2026 | Preclinical | Cancer Biol Ther | Carboplatin plus PARP inhibitor combination tested in HGSC spheroids and organoids. |
| 34321239 | 2021 | Preclinical | Cancer Res | Loss of RAD51C promoter methylation causes PARP inhibitor resistance in HGSC xenograft models. |
| 41465250 | 2025 | Preclinical | Int J Mol Sci | Proteomic analysis of the poly-pharmacological effects of PARP inhibitors in HGSOC cells. |
| 41214101 | 2025 | Preclinical | Sci Rep | Claudin-4 as a regulator of genome stability and immune evasion in HGSC. |
| 40702505 | 2025 | Bioinformatic/preclinical | J Ovarian Res | Cancer stem cell-based subtypes and prognostic model in HGSOC. |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 14172X | Zejula | Tablet 100 mg (as tosilate monohydrate) | Not available in the data compiled for this report |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (PARP inhibitor) |
| Myelosuppression Risk | Medium to high. Haematological toxicity is a recognised concern for this drug class (for example anaemia, thrombocytopenia, neutropenia). |
| Emetogenicity Classification | Low to medium |
| Monitoring Items | FBC (with differential), blood pressure, and liver and renal function. Please refer to the Product Information (PI) for the monitoring schedule. |
| Handling Protection | Please refer to the Product Information (PI) warnings and precautions |
Safety Considerations
Key warnings and contraindications were not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI) for safety information.
Drug interactions: An interaction screen returned 100 potential interactions. The first 20 reviewed include the following.
- Major:
- Deferiprone
- Samarium (153Sm) lexidronam
- Moderate, antithrombotic and antiplatelet agents (bleeding and haematological considerations):
- Acetylsalicylic acid
- Abciximab
- Alteplase
- Antithrombin III human
- Apixaban
- Betrixaban
- Bivalirudin
- Cangrelor
- Caplacizumab
- Cilostazol
- Dipyridamole
- Moderate, radiopharmaceuticals and others:
- Iobenguane (I-131)
- Ibritumomab tiuxetan
- Tositumomab and Tositumomab (I-131)
- Strontium chloride Sr-89
- Palifermin
- Rolapitant
The interacting drugs are largely myelosuppressive agents, radiopharmaceuticals and agents affecting haemostasis. The remaining interactions were not reviewed in detail.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction for cystic neoplasm rests on indirect evidence from serous gynaecological carcinomas. The only directly relevant trial is a recruiting Phase 2 study without results, and the other trials were terminated or withdrawn. The broad “cystic neoplasm” label, the absence of mechanism data and the absence of label safety data mean there is not yet enough to support progression.
To proceed, the following is needed:
- A clearly defined target population (for example, HRD-positive serous carcinoma) in place of the broad “cystic neoplasm” label
- Results from NCT04716686 and other Phase 2/3 data in serous gynaecological cancers
- Mechanism of action data (MOA) and an HRD-based mechanistic rationale
- Warnings and contraindications from the TGA-approved PI, and the approved indication text for ARTG 14172X
- A haematological safety and monitoring plan, including management of interactions with antithrombotic agents
Other predicted indications: The other nine predictions (epiglottis neoplasm, benign neoplasms of the hypopharynx, tongue and floor of mouth, cervical neuroblastoma, tumour of testis and paratestis, inner ear neoplasm, pre-malignant neoplasm, and schwannoma of the jugular foramen) have no trials or literature (L5, prediction only) and are on Hold. For the benign lesions in particular, the risk-benefit balance of a PARP inhibitor with known haematological toxicity is unfavourable.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.