Nintedanib
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
Nintedanib: Dermatofibrosarcoma protuberans
One-Sentence Summary
Nintedanib is an oral triple angiokinase inhibitor, originally used for idiopathic pulmonary fibrosis and non-small cell lung cancer. The TxGNN model predicts it may be effective for dermatofibrosarcoma protuberans (DFSP), but currently there are no registered clinical trials and only 1 indirect review publication supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Dermatofibrosarcoma protuberans |
| TxGNN Prediction Score | 0.9915 |
| Evidence Level | L5 |
| 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 |
Why is This Prediction Reasonable?
Detailed mechanism of action data was not available in the data compiled for this report. Based on known pharmacology, nintedanib is a triple angiokinase inhibitor targeting PDGFR alpha/beta, FGFR 1-3 and VEGFR 1-3.
DFSP is driven by the COL1A1-PDGFB fusion, which causes constitutive PDGFR-beta signalling. Nintedanib inhibits this receptor family, so the prediction is mechanistically plausible. Its antifibrotic and antiproliferative effects on fibroblasts in pulmonary fibrosis also fit with DFSP, a fibroblast-derived tumour.
The one retrieved paper is a general review of PDGFR inhibitors in neoplastic disorders, which is indirect evidence. Imatinib is the established PDGFR-targeted therapy for DFSP, and no nintedanib-specific clinical data were available.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29408302 | 2018 | Review | Pharmacological Research | Reviews small-molecule PDGFR inhibitors in neoplastic disorders. It is indirect evidence and does not report nintedanib-specific data in DFSP. |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 11100F | Ofev | Capsule 100 mg (oral) | Not stated in the data compiled for this report |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-target tyrosine kinase inhibitor) |
| Myelosuppression Risk | Please refer to the Product Information (PI) warnings and precautions |
| Emetogenicity Classification | Please refer to the Product Information (PI) warnings and precautions |
| Monitoring Items | Please refer to the PI; liver function and FBC monitoring are generally relevant for kinase inhibitors |
| Handling Protection | Please refer to the PI and local cytotoxic drug handling policies |
Safety Considerations
- Drug Interactions: 100 interactions were identified in the DDI screen, and the first 20 returned are summarised here.
- Major: Dexamethasone.
- Moderate, bleeding risk (anticoagulants, antiplatelets, thrombolytics): acetylsalicylic acid, abciximab, alteplase, antithrombin III human, apixaban, betrixaban, bivalirudin, cangrelor, caplacizumab, cilostazol, clopidogrel, dalteparin, defibrotide, desirudin, dipyridamole.
- Moderate, other: clarithromycin, cobicistat, naltrexone, rolapitant.
Please refer to the TGA-approved Product Information (PI) for warnings and contraindications, as these were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: The TxGNN score is high (0.9915) and the PDGFR-driven mechanism is plausible, but there are no clinical trials and only one indirect review. Imatinib is already the established targeted therapy for DFSP, so a nintedanib case would need to show added value.
To proceed, the following is needed:
- Nintedanib-specific preclinical data (for example DFSP cell lines or xenograft models with the COL1A1-PDGFB fusion)
- Case series or early-phase trial data in DFSP, ideally imatinib-resistant disease
- Detailed mechanism of action data
- TGA Product Information warnings and contraindications for a safety review
- Review of bleeding risk with anticoagulant and antiplatelet co-medications
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.