Sunitinib
| Evidence Level: L2 | Predicted Indications: 5 |
Table of Contents
Sunitinib: Liposarcoma
One-Sentence Summary
Sunitinib is an oral multitargeted tyrosine kinase inhibitor, originally used to treat renal cell carcinoma and gastrointestinal stromal tumour (GIST). The TxGNN model predicts it may be effective for liposarcoma, with 2 clinical trials (both Phase 2, completed) and 9 publications compiled for this direction. Most of this evidence covers soft tissue sarcomas in general, and only a small part is specific to liposarcoma.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 0.9987 |
| Evidence Level | L2 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| 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, sunitinib is a multitargeted tyrosine kinase inhibitor that acts on VEGFR, PDGFR and KIT. Its efficacy in renal cell carcinoma and GIST is established, and mechanistically it may be applicable to sarcomas through anti-angiogenic and PDGFR-blocking effects.
The link to liposarcoma is indirect, however. Liposarcoma is a heterogeneous disease (well-differentiated/dedifferentiated, myxoid and pleomorphic subtypes). Its drivers include MDM2/CDK4 amplification and the FUS-DDIT3 fusion, which are not the main targets of sunitinib. The high score comes from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, such as general soft tissue sarcoma activity, not biological evidence or a direct mechanism.
Other predicted indications show a stronger mechanistic rationale. Dermatofibrosarcoma protuberans (DFSP) is driven by COL1A1-PDGFB fusion, which activates PDGFRB, a direct sunitinib target. Non-clear-cell and unclassified renal cell carcinoma are extensions of an already approved area. These are beyond the scope of this report but may be worth separate evaluation.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00474994 | Phase 2 | Completed | 53 | Continuous-dose sunitinib in non-GIST sarcomas; liposarcoma is among the enrolled histologies. Single-arm, non-randomized |
| NCT00400569 | Phase 2 | Completed | 48 | Open-label sunitinib in metastatic or unresectable soft tissue sarcoma (leiomyosarcoma, liposarcoma, fibrosarcoma, MFH). Liposarcoma-specific results cannot be isolated from the registry data |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 21154746 | 2011 | Phase 2 trial | Int J Cancer | Sunitinib in relapsed or refractory soft tissue sarcoma, with a focus on leiomyosarcoma, liposarcoma and MFH |
| 23482782 | 2013 | Case report | Anticancer Res | Long-lasting clinical benefit of sunitinib in a heavily pre-treated metastatic liposarcoma |
| 22987955 | 2012 | Review | Ann Oncol | Histology-driven therapy for soft tissue sarcoma; trabectedin is highlighted for liposarcoma |
| 24555529 | 2014 | Review | Expert Rev Anticancer Ther | Emerging therapies for adult soft tissue sarcoma |
| 24712007 | 2014 | Review | Magy Onkol | Medical treatment of soft tissue sarcoma by histological subtype |
| 38254762 | 2024 | Review | Cancers | Genetic, epigenetic and transcriptome alterations in liposarcoma for target therapy selection |
Three further publications were retrieved (a regorafenib trial protocol, a myxoid inflammatory myofibroblastic sarcoma case series and an extraskeletal myxoid chondrosarcoma sequencing study). They concern different drugs or tumour entities and are not listed.
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 208964 | Sutent 25mg Capsule (Pfizer Ltd) | Strip of 7 capsules | Not stated |
| 208965 | Sutent 50mg Capsule (Pfizer Ltd) | Strip of 7 capsules | Not stated |
| 208966 | Sutent 12.5mg Capsule (Pfizer Ltd) | Strip of 7 capsules | Not stated |
| 207188 | Sutib 12.5 Capsule (Glenmark Pharmaceuticals Ltd) | Strip of 7 capsules | Not stated |
| 211416 | Svitinib 25 Capsule (Mylan Pharmaceuticals Pvt Ltd) | Strip of 7 capsules | Not stated |
There are 20 valid single-ingredient registrations in total, covering capsules and tablets in 12.5 mg, 25 mg and 50 mg strengths.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multitargeted tyrosine kinase inhibitor) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions. The knowledge graph links the drug to thrombocytopenia and anaemia as cautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Complete blood count, liver function, thyroid function, cardiac function (including QT interval) and blood pressure |
| Handling Protection | Please refer to the package insert warnings and precautions; handle in line with local oncology drug handling procedures |
Safety Considerations
- Contraindications / cautions (from drug-disease links in the knowledge graph, not label text):
- Cardiac: long QT syndrome (including familial), torsades de pointes, heart failure
- Liver: liver failure, liver disease, drug-induced liver injury, hyperbilirubinaemia (including Gilbert syndrome)
- Endocrine: hypothyroidism, hyperthyroidism, adrenocortical insufficiency
- Blood and other: thrombocytopenia, anaemia, epilepsy, posterior leukoencephalopathy syndrome, pancreatitis
- Drug Interactions: 405 interactions were identified. Of the 20 listed, one is Major (dolasetron, an anti-emetic, likely because of QT prolongation) and the rest are Moderate. Moderate examples include clarithromycin, dexamethasone, famotidine, loperamide, glimepiride and several insulins. Other Moderate entries are laxatives and bowel-preparation agents such as bisacodyl and polyethylene glycol.
- The drug’s known cardiotoxicity (such as a decline in LVEF and hypertension) should also be considered in any sarcoma setting.
Package insert warnings and contraindications for the India products were not available, so please refer to the package insert for the full safety profile.
Conclusion and Next Steps
Decision: Hold
Rationale: The two completed Phase 2 trials are single-arm and enrolled mixed sarcoma populations, so liposarcoma-specific efficacy cannot be separated out. There is no randomized evidence, and the mechanistic link is indirect. The India package insert safety data are also missing, which blocks safety screening. The evidence supports it as a research question rather than a decision to proceed.
To proceed, the following is needed:
- Liposarcoma-specific results (subgroup outcomes) from NCT00474994, NCT00400569 and the published Phase 2 study (PMID 21154746)
- Mechanism of action data (MOA) and a stronger rationale for liposarcoma subtypes (MDM2/CDK4, FUS-DDIT3)
- India package insert warnings and contraindications, to complete safety screening
- Comparison against established sarcoma options such as trabectedin
- A cardiac and hepatic safety monitoring plan, given the QT, heart failure and liver-injury signals
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.