Sunitinib
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Sunitinib: From Renal Cell Carcinoma to Liposarcoma
One-Sentence Summary
Sunitinib is an oral multi-targeted 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 completed Phase 2 clinical trials and 8 publications currently linked to this direction. The evidence comes mostly from mixed-histology sarcoma studies, so it is only moderate.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Renal cell carcinoma (including clear cell type) and gastrointestinal stromal tumour (from the knowledge graph; Singapore licence indication text is not available) |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 99.87% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 7 |
| Recommended Decision | Hold (research question only; see Conclusion) |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, sunitinib is a multi-targeted receptor tyrosine kinase inhibitor acting on VEGFR, PDGFR, KIT, RET and FLT3. It blocks signals that drive tumour blood-vessel growth and cell proliferation. Its efficacy in renal cell carcinoma and in imatinib-resistant GIST is established.
Soft tissue sarcomas, including liposarcoma, can depend on angiogenesis and PDGFR-driven signalling, so mechanistically the drug could be applicable. However, the available studies pool several sarcoma subtypes. Activity in liposarcoma specifically appears limited. Current literature also notes that other agents, such as trabectedin, show stronger histology-specific activity in liposarcoma.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00474994 | Phase 2 | Completed | 53 | Continuous-dosing sunitinib in metastatic, locally advanced or recurrent non-GIST sarcomas; mixed histology, single-arm |
| NCT00400569 | Phase 2 | Completed | 48 | Open-label sunitinib in unresectable or metastatic soft tissue sarcoma (leiomyosarcoma, liposarcoma, fibrosarcoma, MFH); single-arm, small |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 21154746 | 2011 | Phase 2 trial | Int J Cancer | Sunitinib in relapsed or refractory soft tissue sarcoma, focused on leiomyosarcoma, liposarcoma and MFH |
| 38254762 | 2024 | Review | Cancers | Genetic, epigenetic and transcriptome alterations in liposarcoma for target therapy selection |
| 24555529 | 2014 | Review | Expert Rev Anticancer Ther | Emerging therapies for adult soft tissue sarcoma |
| 22987955 | 2012 | Review | Ann Oncol | Histology-driven therapy for sarcomas; trabectedin has high activity in myxoid liposarcoma |
| 24712007 | 2014 | Review | Magyar Onkologia | Medical treatment of soft tissue sarcomas by histological subtype |
| 23482782 | 2013 | Case report | Anticancer Res | Long-lasting clinical benefit of sunitinib in a heavily pre-treated metastatic liposarcoma patient |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN16742P | NIBINASE Hard Gelatin Capsule 25 mg | Capsule | Not stated in the data |
| SIN16743P | NIBINASE Hard Gelatin Capsule 50 mg | Capsule | Not stated in the data |
| SIN16741P | NIBINASE Hard Gelatin Capsule 12.5 mg | Capsule | Not stated in the data |
| SIN16271P | INSUNITINIB Capsule 37.5 mg | Capsule, gelatin coated | Not stated in the data |
| SIN16272P | INSUNITINIB Capsule 50 mg | Capsule, gelatin coated | Not stated in the data |
Two further INSUNITINIB strengths (12.5 mg, 25 mg) are also registered, giving 7 valid single-ingredient registrations in total.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-kinase inhibitor), not a conventional cytotoxic |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions (thrombocytopenia and anaemia appear among the listed contraindicated conditions) |
| 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 heart failure signs), blood pressure |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Conditions flagged as contraindications in the knowledge graph (not label text):
- Cardiac: long QT syndrome, torsades de pointes, heart failure
- Liver: liver failure, liver disease, drug-induced liver injury, hyperbilirubinaemia, Gilbert syndrome
- Blood: thrombocytopenia, anaemia
- Endocrine: hypothyroidism, hyperthyroidism, adrenocortical insufficiency
- Other: epilepsy, pancreatitis, gallbladder disease, posterior leukoencephalopathy syndrome
- Drug Interactions: 100 interactions were recorded. Among those listed, dolasetron is rated Major (QT-related concern). Moderate interactions include clarithromycin, dexamethasone, famotidine, loperamide, palonosetron, several laxatives and bowel-preparation agents, and sulfonylureas and insulins (glycaemic effects).
Package insert warnings were not available, so please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: Only two small, single-arm, mixed-histology Phase 2 trials support the prediction, and activity in liposarcoma specifically appears limited. Established alternatives such as trabectedin have stronger histology-specific data. The safety profile also includes cardiac, hepatic and haematological concerns. The knowledge-graph evidence flags this as a research question rather than a candidate ready for adoption.
To proceed, the following is needed:
- Liposarcoma-specific response data (subtype breakdown) from the existing Phase 2 trials
- Package insert warnings and contraindications from HSA, and mechanism of action data from DrugBank
- A comparison against current standard options for liposarcoma
- A cardiac, hepatic and haematological safety monitoring plan
Other predictions of note (for reference):
- Unclassified renal cell carcinoma has the strongest supporting evidence among the new indications (L2, "Proceed with Guardrails"). The randomised ASPEN and ESPN Phase 2 trials and several prospective Phase 2 studies evaluated sunitinib in non-clear cell RCC, but the evidence is pooled across subtypes and activity is modest.
- Dermatofibrosarcoma protuberans has a strong mechanistic basis (COL1A1-PDGFB fusion drives PDGFRB activation). Evidence is limited to a small retrospective series and case reports, and imatinib remains the standard targeted option.
- Renal carcinoma is the already approved original indication, so it serves as confirmation rather than repurposing.
- Several other predictions (ovarian myxoid liposarcoma, angiolipoma, heart fibrosarcoma, renal cell carcinoma associated with neuroblastoma) have little or no supporting evidence and are rated Hold.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.