Niraparib

Evidence Level: L5

Predicted Indications: 10

Niraparib

Pharmacist Assessment Report

Niraparib: From Ovarian and Peritoneal Cancer to Epiglottis Neoplasm

One-Sentence Summary

Niraparib is a PARP inhibitor originally used for malignant epithelial tumours of the ovary and primary peritoneal carcinoma. The TxGNN model’s top-ranked prediction is Epiglottis Neoplasm, but there are 0 clinical trials and 0 publications supporting it, so this is a model-only prediction. The most evidence-backed signal among the top 10 predictions is for Cystic Neoplasm (rank 2), which is supported by 3 clinical trials and 10 publications, all centred on serous gynaecological carcinomas. These are reported below as a secondary finding.

Quick Overview

Item	Content
Original Indication	Malignant epithelial tumour of the ovary; primary peritoneal carcinoma (the Canadian licence records contain no indication text)
Predicted New Indication	Epiglottis neoplasm
TxGNN Prediction Score	0.9999
Evidence Level	L5
Canada Market Status	Marketed (marketed DINs: 3 of 3)
Number of DINs	3 (marketed: 3)
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on general knowledge, niraparib is a PARP1/2 inhibitor. It acts through synthetic lethality in tumours with homologous recombination deficiency (HRD), and its efficacy in ovarian and peritoneal cancers is established.

For epiglottis neoplasm, nothing in the compiled data supports this mechanism. The score of 0.9999 comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence. No trials, publications or similarity analysis with the original indications back it up. The prediction should therefore be treated as a hypothesis, not as evidence of benefit.

The second-ranked prediction, cystic neoplasm, is more informative. This label is generic, and the supporting studies concern serous gynaecological carcinomas (endometrial serous carcinoma and high-grade serous ovarian carcinoma). These tumours share molecular features with ovarian cancer, such as chromosomal instability and frequent HRD. The link is therefore indirect and works through serous histology. The ovarian and peritoneal indications are already original indications, so the genuinely new signal is mainly endometrial serous carcinoma.

Clinical Trial Evidence

No clinical trials are registered for epiglottis neoplasm (the primary prediction).

For the rank 2 prediction (cystic neoplasm), the following trials were identified:

Trial Number	Phase	Status	Enrollment	Key Findings
NCT04716686	Phase 2	Recruiting	83	Niraparib monotherapy as maintenance and recurrent treatment in endometrial serous carcinoma. No results yet.
NCT04159155	Phase 2/3	Terminated	11	Canadian multi-arm, multi-stage trial of front-line and maintenance treatment in serous or p53-mutant endometrial cancer. Terminated early, so no interpretable efficacy data.
NCT05289648	Early Phase 1	Withdrawn	0	Preoperative niraparib in high-grade endometrial cancer. Withdrawn with no participants, so no data.

Literature Evidence

No publications were found for epiglottis neoplasm.

For the rank 2 prediction (cystic neoplasm), the most relevant publications are:

PMID	Year	Type	Journal	Key Findings
40473279	2025	Study protocol (Phase 2)	BMJ Open	Protocol for niraparib maintenance in stage III/IV, chemo-naïve recurrent or platinum-sensitive recurrent uterine serous carcinoma.
42442041	2026	Cohort	Gynecologic Oncology	Real-world HRD testing in BRCA1/2 wild-type high-grade serous carcinoma, with MYC amplification explored as a surrogate marker.
41323499	2025	Cohort	Pathology Oncology Research	Comprehensive genomic profiling for HRD to guide PARP inhibitor recommendations in ovarian cancer.
42157333	2026	Cohort	Clinical Epigenetics	Nomogram based on HRR gene promoter methylation to predict PARP inhibitor efficacy in high-grade serous ovarian cancer.
31466953	2019	Case report	BMJ Case Reports	Niraparib maintenance therapy in a patient with ovarian cancer and brain metastases.
41520277	2026	Preclinical	Cancer Biology & Therapy	Carboplatin plus PARP inhibitor combination in high-grade serous carcinoma spheroids and organoids.
34321239	2021	Preclinical	Cancer Research	Loss of RAD51C promoter methylation causes PARP inhibitor resistance in high-grade serous ovarian carcinoma.
41465250	2025	Preclinical	International Journal of Molecular Sciences	Proteomic analysis of the poly-pharmacological effects of PARP inhibitors in high-grade serous ovarian cancer cells.

These publications concern serous gynaecological cancers and PARP inhibitor biomarkers. None addresses epiglottis neoplasm.

Canada Market Information

DIN	Product Name	Dosage Form	Approved Indication
02530031	ZEJULA	Not specified	Not specified
02538555	AKEEGA	Not specified	Not specified
02538563	AKEEGA	Not specified	Not specified

All three licences are valid authorisations.

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (PARP inhibitor)
Myelosuppression Risk	Medium to high. Haematological toxicity is expected with PARP inhibitors, and there is a risk of myelodysplastic syndrome or acute myeloid leukaemia.
Emetogenicity Classification	Low to medium
Monitoring Items	Complete blood count, blood pressure, liver and renal function
Handling Protection	Please refer to the package insert warnings and precautions

Safety Considerations

Drug Interactions: 100 interactions were recorded in the interaction database. The sample reviewed includes two Major interactions, with deferiprone and samarium (153Sm) lexidronam. Most others are Moderate, and many involve drugs affecting bleeding or clotting, such as acetylsalicylic acid, apixaban, alteplase, abciximab, bivalirudin, cilostazol and dipyridamole. Radiopharmaceuticals such as iobenguane (I-131), tositumomab and strontium chloride Sr-89 are also listed, along with ibritumomab tiuxetan, rolapitant and palifermin.

Warnings and contraindications from the Canadian package insert were not available for this report. Please refer to the package insert for these details.

Conclusion and Next Steps

Decision: Hold

Rationale: The top-ranked prediction, epiglottis neoplasm, rests on a TxGNN model (deep learning) score alone, which may reflect similarities the model learned between related diseases, not biological evidence, with no trials or publications. For the ten predictions reviewed, only cystic neoplasm has supporting studies, and these are indirect (serous endometrial carcinoma). Most of that evidence is early or inconclusive: one Phase 2 trial is still recruiting, one was terminated early, and one was withdrawn. The remaining eight predictions, including the benign lesions, have no evidence, and the toxicity of a PARP inhibitor is hard to justify for them.

To proceed, the following is needed:

Canadian package insert warnings and contraindications (a blocking gap for safety screening)
Detailed mechanism of action data
Results from NCT04716686 (endometrial serous carcinoma) before considering this as a research direction
Any biological or clinical rationale for epiglottis neoplasm, such as HRD prevalence or preclinical data
Approved indication text and dosage forms for the Canadian licences
Disclaimer

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