Sunitinib
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Sunitinib: From Renal Cell Carcinoma / GIST to Liposarcoma
One-Sentence Summary
Sunitinib is a multi-targeted tyrosine kinase inhibitor with established use in renal cell carcinoma (RCC) and gastrointestinal stromal tumour (GIST). The TxGNN model predicts it may also be effective for Liposarcoma, with 3 clinical trials and 9 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Renal cell carcinoma and gastrointestinal stromal tumour (GIST) — inferred from evidence-pack trial context; no structured licence text was provided (see Data Gap note below) |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 99.87% |
| Evidence Level | L2 |
| UK Market Status | Not Marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action (MOA) data from DrugBank is not currently available for Sunitinib in this Evidence Pack. Based on the mechanistic information that is available, Sunitinib is a multi-targeted tyrosine kinase inhibitor (TKI) that blocks VEGFR1-3, PDGFRα/β, KIT, FLT3 and RET signalling — a mechanism confirmed by the wide range of RCC and GIST trials referenced throughout this pack.
Sunitinib’s established efficacy in RCC relies on anti-angiogenic activity via VEGFR blockade. Liposarcoma — particularly the myxoid/round cell subtype — is characterised by high angiogenic activity and PDGFR pathway activation, which overlaps directly with Sunitinib’s inhibitory spectrum. This shared vascular and growth-factor signalling biology is the pharmacological basis for extending Sunitinib from renal and gastrointestinal tumours into selected soft-tissue sarcomas, including liposarcoma.
This mechanistic plausibility is reinforced by real clinical experience: liposarcoma is one of the histological subtypes explicitly evaluated in two completed Phase 2 non-GIST sarcoma trials referenced below, and by a dedicated case report describing durable clinical benefit in metastatic liposarcoma.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT00474994 | Phase 2 | Completed | 53 | Multicentre continuous-dosing study of sunitinib in non-GIST sarcomas (including liposarcoma); evaluated tumour growth inhibition and anti-angiogenic effect |
| NCT00400569 | Phase 2 | Completed | 48 | Open-label study of sunitinib malate in unresectable/metastatic soft tissue sarcoma, covering leiomyosarcoma, liposarcoma, fibrosarcoma and MFH |
| NCT02048371 | Phase 2 | Completed | 131 | SARC024 basket study of regorafenib (not sunitinib) in selected sarcoma subtypes; included as mechanistic-class reference only (Grade C relevance) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 21154746 | 2011 | Phase 2 trial | International Journal of Cancer | Phase II study of sunitinib malate in relapsed/refractory soft tissue sarcoma, focused on leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma |
| 25884155 | 2015 | Trial Protocol | BMC Cancer | REGOSARC trial protocol: angiogenesis-targeted therapy (regorafenib, mechanistic class comparator to sunitinib) in advanced soft tissue sarcoma |
| 38254762 | 2024 | Review | Cancers | Genetic, epigenetic and transcriptome alterations in liposarcoma relevant to target therapy selection |
| 24555529 | 2014 | Review | Expert Review of Anticancer Therapy | Emerging systemic therapies for adult soft tissue sarcoma, including targeted agents |
| 22987955 | 2012 | Review | Annals of Oncology | Histology-driven medical treatment of soft tissue sarcomas, noting trabectedin/sunitinib-class activity by subtype |
| 23482782 | 2013 | Case Report | Anticancer Research | Long-lasting clinical benefit of sunitinib malate in a heavily pre-treated metastatic liposarcoma patient |
| 38717131 | 2024 | Not yet classified | American Journal of Surgical Pathology | Clinicopathologic analysis of a distinctive myxoid inflammatory myofibroblastic sarcoma subtype |
| 24712007 | 2014 | Not yet classified | Magyar Onkologia | Histological subtype-based medical treatment approach for soft tissue sarcomas |
| 28423517 | 2017 | Not yet classified | Oncotarget | Next-generation sequencing of extraskeletal myxoid chondrosarcoma, including sunitinib response evaluation |
UK Market Information
No marketing authorisation for Sunitinib is currently held in the United Kingdom according to this Evidence Pack (market status: Not Marketed, 0 authorisations on record). No product, dosage form or licensed indication data is therefore available to summarise.
Cytotoxicity
This section is included because Sunitinib is an established antineoplastic agent (multi-targeted tyrosine kinase inhibitor used in oncology indications such as RCC and GIST).
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-targeted tyrosine kinase inhibitor with anti-angiogenic activity) |
| Myelosuppression Risk | Please refer to the SmPC warnings and precautions |
| Emetogenicity Classification | Please refer to the SmPC warnings and precautions |
| Monitoring Items | Please refer to the SmPC warnings and precautions |
| Handling Protection | Please refer to the SmPC warnings and precautions |
Safety Considerations
Please refer to the SmPC and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The lead predicted indication (liposarcoma) is supported by an evidence level of L2 — including two completed Phase 2 trials that explicitly enrolled liposarcoma patients and a dedicated Phase 2 study plus case report describing clinical benefit — giving a mechanistically coherent and partially clinically demonstrated repurposing signal. However, this Evidence Pack has an unresolved Blocking data gap (TFDA/MHRA product warnings and contraindications, DG001) that prevents a full S1 safety review, alongside a High-severity gap in mechanism-of-action data (DG002).
To proceed, the following is needed:
- Resolve DG001: obtain the UK/MHRA-approved product information (SmPC) to complete safety screening before any clinical evaluation proceeds
- Resolve DG002: obtain confirmed DrugBank/SmPC mechanism-of-action data to strengthen the mechanistic rationale
- Formal drug interaction (DDI) data, as the current query returned no results
- Confirm route of administration compatibility between the original (oral, RCC/GIST) and proposed liposarcoma use, currently marked “pending” in this pack
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.