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 for 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 (non-GIST sarcoma) and a published Phase 2 study providing a direct but limited signal.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 0.9987 |
| Evidence Level | L2 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| 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 pharmacology, sunitinib inhibits VEGFR and PDGFR (and KIT), pathways involved in tumour angiogenesis and growth signalling. Its efficacy in renal cell carcinoma and imatinib-resistant GIST is established.
Angiogenesis and PDGFR/VEGFR signalling also play a role in sarcoma biology, which is the mechanistic basis for testing sunitinib in soft tissue sarcomas. Liposarcoma is, however, only one subgroup in the sarcoma studies, and the data compiled suggest activity there appears limited. Sarcoma treatment is increasingly driven by histological subtype, so extrapolation from kidney cancer or GIST should be made cautiously.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00474994 | Phase 2 | Completed | 53 | Continuous-dose sunitinib in metastatic, locally advanced or recurrent non-GIST sarcomas; liposarcoma is among the enrolled histologies |
| NCT00400569 | Phase 2 | Completed | 48 | Open-label single-site study in unresectable or metastatic soft tissue sarcoma (leiomyosarcoma, liposarcoma, fibrosarcoma, MFH); liposarcoma-specific data not clear from the available summary |
No ANZCTR identifiers were available in the data compiled.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 21154746 | 2011 | Phase 2 trial | Int J Cancer | Single-institution study of sunitinib in relapsed or refractory soft tissue sarcoma, focused on leiomyosarcoma, liposarcoma and MFH |
| 22987955 | 2012 | Review | Ann Oncol | Soft tissue sarcoma therapy is histology-driven; trabectedin is highlighted for liposarcoma |
| 24555529 | 2014 | Review | Expert Rev Anticancer Ther | Emerging therapies for adult soft tissue sarcoma |
| 24712007 | 2014 | Review | Magy Onkol | Histology-based medical treatment of soft tissue sarcoma |
| 38254762 | 2024 | Review | Cancers | Genetic, epigenetic and transcriptome alterations in liposarcoma for target therapy selection |
| 23482782 | 2013 | Case report | Anticancer Res | Long-lasting clinical benefit of sunitinib in a heavily pre-treated metastatic liposarcoma |
| 25884155 | 2015 | Trial protocol | BMC Cancer | REGOSARC protocol (regorafenib, not sunitinib) in advanced soft tissue sarcoma |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| ARTG 10004M | Sunitinib Sandoz | Capsule 12.5 mg | Not recorded in the data compiled |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multitargeted tyrosine kinase inhibitor) |
| Myelosuppression Risk | Please refer to the Product Information (PI) warnings and precautions |
| Emetogenicity Classification | Please refer to the Product Information (PI) warnings and precautions |
| Handling Protection | Follow local handling requirements for antineoplastic agents; refer to the PI |
Safety Considerations
- Disease associations flagged by the TxGNN model (deep learning), not label text: long QT syndrome, torsades de pointes, heart failure, liver failure and drug-induced liver injury, thrombocytopenia, anaemia, hypothyroidism and hyperthyroidism, adrenocortical insufficiency, pancreatitis, epilepsy, hyperbilirubinaemia (including Gilbert syndrome), gallbladder disease, potassium deficiency, and posterior leukoencephalopathy syndrome. These associations may reflect similarities the model learned between related diseases, not biological evidence.
- Drug interactions: 100 interactions were identified, of which 20 were listed. The only Major one in that list is dolasetron (QT-related concern). Moderate interactions include clarithromycin, dexamethasone, palonosetron, famotidine, loperamide, several insulins, sulfonylureas (glimepiride, chlorpropamide) and bowel-preparation or laxative agents (bisacodyl, picosulfuric acid, sodium sulfate, polyethylene glycol).
- Sunitinib-induced thrombotic microangiopathy has been reported in the literature (PMID 27072203).
Label warnings and contraindications were not available. Please refer to the TGA-approved Product Information (PI) for full safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: Two completed Phase 2 trials and one published Phase 2 study give a direct clinical signal, but liposarcoma is only one subgroup, activity appears limited, and no histology-specific results were available in the data compiled. The Australian licence is marketed, but its approved indication text and the label safety data are missing. The data therefore support a research question rather than a clinical recommendation.
To proceed, the following is needed:
- Liposarcoma-specific response and survival data from NCT00474994, NCT00400569 and PMID 21154746
- Comparison against established liposarcoma options (e.g. trabectedin, doxorubicin-based regimens)
- Mechanism of action data and the TGA Product Information (warnings, contraindications, approved indications)
- A QT, cardiac and hepatic monitoring plan, plus a review of interacting medicines
Other predicted indications: “unclassified renal cell carcinoma” and “renal carcinoma” were assessed as Proceed with Guardrails, but they largely sit within the already-approved renal cell carcinoma space rather than representing true repurposing. Dermatofibrosarcoma protuberans (imatinib-resistant) is a Research Question with a strong PDGFR rationale. The remaining predictions have little or no supporting evidence (Hold).
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.