Imatinib
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Imatinib: From Chronic Myelogenous Leukaemia and GIST to Heart Fibrosarcoma
One-Sentence Summary
Imatinib is a tyrosine kinase inhibitor originally used for BCR-ABL1-positive chronic myelogenous leukaemia, gastrointestinal stromal tumour (GIST), dermatofibrosarcoma protuberans and related conditions. The TxGNN model predicts it may be effective for heart fibrosarcoma, but the evidence is thin: 0 clinical trials and 1 publication (a general review) currently support this specific prediction. Among the other top-ranked predictions, only liposarcoma has relevant Phase 2 trial data, and that evidence comes from mixed-histology sarcoma studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Singapore licence records. The knowledge graph lists chronic myelogenous leukaemia (BCR-ABL1 positive), GIST, dermatofibrosarcoma protuberans, systemic mastocytosis, and hypereosinophilic syndromes |
| Predicted New Indication | Heart fibrosarcoma |
| TxGNN Prediction Score | 99.94% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 13 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on published literature, imatinib inhibits the tyrosine kinases BCR-ABL, KIT and PDGFR. Its efficacy in GIST (KIT-driven) and dermatofibrosarcoma protuberans (DFSP, driven by the COL1A1-PDGFB fusion that activates PDGFRB) is established.
Fibrosarcoma is a fibroblast-derived sarcoma, which is biologically close to DFSP. In DFSP, the fibrosarcomatous variant is driven by the same PDGFB/PDGFRB signalling that imatinib blocks. This offers a plausible but indirect link to fibrosarcoma at other sites.
There are important limits. Conventional fibrosarcoma generally lacks the COL1A1-PDGFB fusion, so any benefit would likely apply only to a molecularly defined subset. No cardiac-specific data exist for imatinib. The prediction should be read as a hypothesis, not as evidence of benefit.
Clinical Trial Evidence
Currently no related clinical trials are registered for heart fibrosarcoma.
For context, trials linked to other top-ranked predictions are listed below. They are mixed-histology studies and do not show disease-specific results.
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00154388 | Phase 2 | Completed | 185 | Basket study of imatinib in life-threatening rare malignancies; linked to kidney fibrosarcoma and liposarcoma, with no organ- or subtype-specific results shown |
| NCT00031915 | Phase 2 | Completed | Not reported | Imatinib in metastatic or unresectable soft tissue and bone sarcomas; liposarcoma may be among the histologies |
| NCT00006357 | Phase 1/2 | Completed | 91 | Dose-finding and efficacy study in advanced soft tissue sarcoma; subtype efficacy not shown |
Literature Evidence
For heart fibrosarcoma, only one publication is available. Key publications for the related predictions are also shown.
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 18623899 | 2008 | Review | Prescrire International | Heart fibrosarcoma: review of imatinib's expanded indications, concluding the evidence for the new indications is not robust |
| 39904126 | 2025 | Guideline | European Journal of Cancer | Fibroblastic neoplasm / DFSP: European guideline supports imatinib for unresectable or metastatic DFSP, an existing indication |
| 19451433 | 2009 | Phase 2 trial | Journal of Clinical Oncology | Liposarcoma: multicentre Phase 2 trial of imatinib across 10 sarcoma subtypes |
| 25852058 | 2015 | Preclinical | Molecular Cancer Therapeutics | Conventional fibrosarcoma: CDKN2A/p16 loss and CDK4 dependence as a resistance mechanism in imatinib-resistant DFSP |
| 30901500 | 2019 | Preclinical | Drug Development Research | Conventional fibrosarcoma: liposomal and nanocochleate imatinib plus dexketoprofen tested against fibrosarcoma |
| 42062942 | 2026 | Cohort study | BMC Cancer | Conventional fibrosarcoma: 153 Chinese DFSP patients treated with Mohs surgery and postoperative imatinib |
| 40558511 | 2025 | Preclinical | Cells | Fibroblastic neoplasm: patient-derived cell lines used to predict imatinib sensitivity in DFSP |
Singapore Market Information
Imatinib has 13 valid single-ingredient registrations in Singapore, with no cancelled licences. Approved indication text is not recorded in the licence data. The main authorisations are:
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13279P | Glivec Film Coated Tablet 100mg | Film-coated tablet | Not recorded |
| SIN13280P | Glivec Film Coated Tablet 400mg | Film-coated tablet | Not recorded |
| SIN15356P | Vativio Film Coated Tablet 100mg | Film-coated tablet | Not recorded |
| SIN15357P | Vativio Film Coated Tablet 400mg | Film-coated tablet | Not recorded |
| SIN15107P | Imatinib-AFT Capsules 100mg | Capsule | Not recorded |
Other registered products include Veenat (100 mg and 400 mg), Hetero Imatinib (100 mg and 400 mg), Imatiqual (100 mg and 400 mg), Neopax 400 mg and Imatinib-AFT 400 mg capsules. All are oral formulations.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (tyrosine kinase inhibitor) |
| Myelosuppression Risk | Medium. The knowledge graph flags neutropenia, thrombocytopenia, anaemia and agranulocytosis as cautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | CBC with differential, liver function, renal function, fluid retention and cardiac status |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Key Warnings and Contraindications (label): Label-based data were not available. Please refer to the package insert.
- Conditions flagged as cautions in the knowledge graph (not label text): liver failure and liver disease, kidney disease, congestive heart failure and other heart failure, heart valve disease, pericardial effusion, congenital heart disease, coronary artery disease, hypertension, thrombocytopenia, neutropenia, agranulocytosis, anaemia, hyperbilirubinaemia (including Gilbert syndrome), pulmonary edema, brain edema, diabetes mellitus, diabetic ketoacidosis, obesity, active peptic ulcer disease and hypophosphataemia. The cardiac items deserve particular attention for any cardiac tumour use.
- Drug Interactions: 100 interactions were found. Major-level interactions include eliglustat and naloxegol. Moderate-level interactions include corticosteroids (hydrocortisone, dexamethasone, betamethasone, triamcinolone, budesonide), clarithromycin, cimetidine, aprepitant, morphine, proton pump inhibitors (lansoprazole, dexlansoprazole), and the antidiabetic drugs pioglitazone, glimepiride and saxagliptin.
- Reported adverse event: A case report describes imatinib-induced DRESS (drug reaction with eosinophilia and systemic symptoms) in a patient with DFSP, who was successfully managed with desensitisation.
Conclusion and Next Steps
Decision: Hold
Rationale: The heart fibrosarcoma prediction has a very high model score, but it rests on one general review and no clinical trials. The mechanistic link (PDGFRB activation) applies mainly to DFSP, which is already an existing imatinib indication, so it does not amount to new repurposing evidence. Among the other predictions, liposarcoma has the most trial activity (three Phase 1/2 or Phase 2 studies), but these are mixed-histology studies and liposarcoma is typically driven by MDM2/CDK4 rather than KIT/PDGFR.
To proceed, the following is needed:
- Package insert warnings and contraindications from HSA (currently a blocking gap for safety screening)
- Mechanism of action data from DrugBank
- Molecular profiling (for example PDGFB/PDGFRB fusion or KIT/PDGFRA status) of any fibrosarcoma subset considered for treatment
- Subtype-level results from the mixed-histology sarcoma trials (NCT00031915, NCT00006357, NCT00154388)
- A cardiac safety assessment, given the cardiac cautions listed above
- Registration and approved-indication wording for the Singapore licences, which is not recorded in the current data
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.