Nintedanib
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
- Nintedanib
- Nintedanib: From Non-Small Cell Lung Carcinoma and Idiopathic Pulmonary Fibrosis to Dermatofibrosarcoma Protuberans
Nintedanib: From Non-Small Cell Lung Carcinoma and Idiopathic Pulmonary Fibrosis to Dermatofibrosarcoma Protuberans
One-Sentence Summary
Nintedanib was originally used for lung diseases, including non-small cell lung carcinoma and idiopathic pulmonary fibrosis. The TxGNN model predicts it may be effective for Dermatofibrosarcoma Protuberans (DFSP), but there are currently 0 clinical trials and only 1 publication (an indirect review) supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Non-small cell lung carcinoma, lung cancer, idiopathic pulmonary fibrosis, acute interstitial pneumonia, idiopathic interstitial pneumonia (the Singapore licence records contain no approved indication text) |
| Predicted New Indication | Dermatofibrosarcoma protuberans |
| TxGNN Prediction Score | 99.15% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| 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 known information, nintedanib is an oral multi-kinase inhibitor that blocks PDGFR alpha/beta, VEGFR and FGFR. It is used in fibrosing lung disease and lung cancer, and mechanistically may be applicable to DFSP.
DFSP is driven by the COL1A1-PDGFB fusion, which causes constitutive PDGFR-beta signalling. Because nintedanib inhibits PDGFR, there is a plausible mechanistic rationale. Its anti-fibroblast activity, the basis of its use in pulmonary fibrosis, is also consistent with a fibroblastic tumour.
However, the link is indirect. Imatinib is the established PDGFR-targeted agent for this disease, and no nintedanib-specific clinical data are available. The prediction should therefore be treated as a research question rather than a clinical recommendation.
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. This is indirect evidence and does not report nintedanib-specific data in DFSP. |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14922P | OFEV Soft Capsules 150 mg | Capsule, liquid filled | Not available |
| SIN14921P | OFEV Soft Capsules 100 mg | Capsule, liquid filled | Not available |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-kinase inhibitor: VEGFR, FGFR, PDGFR) |
| 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: 100 interactions were identified in the interaction screening. The main ones listed include:
- Major: Dexamethasone
- Moderate, antithrombotic and anticoagulant agents (possible additive bleeding risk): 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 package insert for other safety information, including warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction score is high (99.15%), and the PDGFR-driven biology of DFSP gives a plausible mechanistic rationale. However, there are no clinical trials and the only literature is an indirect review. Imatinib is already the established PDGFR-targeted option, and the package insert safety data are missing.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA (a blocking data gap for safety screening)
- Detailed mechanism of action data (MOA)
- Preclinical data (for example, DFSP cell lines or models) or case-level clinical data on nintedanib in DFSP
- A comparison against imatinib to define where nintedanib could add value, such as imatinib-resistant disease
- A review of the bleeding-risk interactions with anticoagulants and antiplatelet agents, which matter in a tumour setting
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.