Nintedanib
| Evidence Level: L5 | Predicted Indications: 3 |
Table of Contents
Nintedanib: Dermatofibrosarcoma protuberans
One-Sentence Summary
Nintedanib was originally used to treat idiopathic pulmonary fibrosis and non-small cell lung cancer. The TxGNN model predicts it may be effective for dermatofibrosarcoma protuberans (DFSP), but at present there are 0 clinical trials and only 1 publication (an indirect review) 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 |
| Canada Market Status | Marketed (marketed DINs: 6 of 6) |
| Number of DINs | 6 (marketed: 6) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the compiled data. Based on known pharmacology, nintedanib is a triple angiokinase inhibitor that blocks VEGFR1-3, FGFR1-3 and PDGFR-alpha/beta. Its efficacy in pulmonary fibrosis and lung cancer is established, and it may be mechanistically applicable to DFSP.
DFSP is driven by the COL1A1-PDGFB fusion gene. This fusion produces constitutive PDGFB autocrine activation of PDGFR-beta. Because nintedanib inhibits PDGFR, it plausibly targets this pathway. Its antifibrotic and antiangiogenic activity adds a general biological rationale.
However, the link is indirect. The only supporting item is a 2018 review on small-molecule PDGFR inhibitors, and there are no nintedanib-specific clinical data for DFSP. Imatinib is already the established PDGFR-directed therapy for DFSP, so nintedanib would need to show a clear advantage, for example in imatinib-resistant disease.
Other top-ranked predictions (liposarcoma, fibrosarcoma subtypes, fibroblastic neoplasm) have no trials or literature.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 29408302 | 2018 | Review | Pharmacological Research | Reviews the role of small-molecule PDGFR inhibitors in neoplastic disorders. It supports PDGFR as a target but contains no nintedanib-specific DFSP data. |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02443066 | OFEV | Not listed | Not listed |
| 02443074 | OFEV | Not listed | Not listed |
| 02526891 | AURO-NINTEDANIB | Not listed | Not listed |
| 02526905 | AURO-NINTEDANIB | Not listed | Not listed |
| 02550849 | JAMP NINTEDANIB | Not listed | Not listed |
One further licence (DIN 02540762, JAMP NINTEDANIB) is also valid, giving 6 valid single-ingredient licences in total.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-target tyrosine kinase / angiokinase inhibitor), not a conventional cytotoxic |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: The interaction screen returned 100 interactions in total. The 20 reviewed include one Major and 19 Moderate interactions.
- Major: Dexamethasone.
- Moderate, bleeding-risk related (antithrombotics and anticoagulants): acetylsalicylic acid, abciximab, alteplase, antithrombin III human, apixaban, betrixaban, bivalirudin, cangrelor, caplacizumab, cilostazol, clopidogrel, dalteparin, defibrotide, desirudin and dipyridamole.
- Moderate, other: clarithromycin, cobicistat, naltrexone and rolapitant.
Package-insert warnings and contraindications were not available. Please refer to the package insert for these.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction has a plausible mechanism through PDGFR inhibition in COL1A1-PDGFB-driven DFSP. However, the evidence is limited to one indirect review, with no clinical trials. Imatinib is already the established therapy, so the added value of nintedanib is unclear.
To proceed, the following is needed:
- Health Canada package insert warnings and contraindications (a blocking gap for safety screening)
- Detailed mechanism of action data
- Preclinical data (for example, DFSP cell lines or imatinib-resistant models) or case series with nintedanib
- A defined clinical niche, such as imatinib-resistant or unresectable DFSP
- Review of the bleeding-risk interactions with antithrombotic drugs
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.