Sorafenib
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Sorafenib: From Hepatocellular Carcinoma to Liposarcoma
One-Sentence Summary
Sorafenib is a multikinase inhibitor originally used to treat hepatocellular carcinoma, renal cell carcinoma and thyroid carcinoma. The TxGNN model predicts it may be effective for liposarcoma, but the supporting evidence is indirect: 1 Phase 2 clinical trial in advanced soft tissue sarcomas (liposarcoma is only one subgroup) and 8 publications, most of them reviews or preclinical studies.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hepatocellular carcinoma, renal cell carcinoma, thyroid carcinoma (the Singapore licence records do not contain indication text) |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 99.82% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 3 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Sorafenib is a multikinase inhibitor that blocks the RAF/MEK/ERK signalling pathway and receptors involved in tumour blood-vessel growth (VEGFR, PDGFR, KIT). Angiogenesis and MAPK signalling are plausible drivers in soft tissue sarcomas. A laboratory study showed that sorafenib inhibited growth and MAPK signalling in cell lines that included dedifferentiated liposarcoma.
The original indications (liver, kidney and thyroid cancers) are all solid tumours that depend on angiogenesis and kinase signalling. This gives a mechanistic reason to test sorafenib in sarcomas. However, soft tissue sarcoma treatment is increasingly driven by histological subtype, and liposarcoma-specific activity of sorafenib has not been clearly established. The prediction should therefore be considered a hypothesis, not a confirmed benefit.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00217620 | Phase 2 | Completed | 51 | Single-agent sorafenib in advanced soft tissue sarcomas. Liposarcoma is one subgroup and no subtype-specific results are available in the compiled data. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 21751200 | 2012 | Phase 2 trial (SWOG S0505) | Cancer | Phase 2 intergroup trial of sorafenib in advanced soft tissue sarcomas; sorafenib targets RAF, VEGFR1-3, PDGFR-B, FLT3 and KIT. |
| 24554062 | 2014 | Phase 1 trial | Ann Surg Oncol | Neoadjuvant radiotherapy plus sorafenib in locally advanced extremity soft tissue sarcoma. |
| 22987955 | 2012 | Review | Ann Oncol | Soft tissue sarcoma therapy is increasingly histology-driven; trabectedin is highlighted for liposarcoma. |
| 24712007 | 2014 | Review | Magy Onkol | Histology-based medical treatment of soft tissue sarcomas. |
| 18413802 | 2008 | Preclinical | Mol Cancer Ther | Sorafenib inhibited growth and MAPK signalling in MPNST and dedifferentiated liposarcoma cell lines. |
| 23416162 | 2013 | Preclinical | Am J Pathol | Dedifferentiated liposarcoma xenograft models; response to PI3K pathway inhibition. |
| 36003796 | 2022 | Review | Front Oncol | Sarcoma PDOX models and palbociclib combinations (not sorafenib-specific). |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN13339P | NEXAVAR TABLET 200 mg | Film-coated tablet | Not recorded in the compiled data |
| SIN16485P | INFENIB FILM COATED TABLET 200MG | Film-coated tablet | Not recorded in the compiled data |
| SIN16774P | SORAVAR 200 FILM COATED TABLET 200 MG | Film-coated tablet | Not recorded in the compiled data |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multikinase inhibitor), not a conventional cytotoxic |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions. The knowledge graph lists thrombocytopenia, neutropenia and agranulocytosis among its contraindication-linked conditions. |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Complete blood count, liver function, blood pressure, and cardiac status (based on the knowledge-graph flags below) |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Contraindication-linked conditions (knowledge graph, not label text): hypertension, liver failure, thrombocytopenia, neutropenia, agranulocytosis, blood coagulation disease, acute coronary syndrome, coronary artery disease, myocardial infarction, myocardial ischaemia, anaemia, hypophosphataemia, pancreatitis, and anxiety/neurotic/dysthymic disorders.
- Drug Interactions: 100 interactions were found in total. Examples:
- Major: dolasetron.
- Moderate: famotidine, loperamide, dexamethasone, clarithromycin, levofloxacin, palonosetron, naltrexone, bisacodyl and several laxatives.
- Minor: dapagliflozin, metronidazole, naloxegol.
Package insert warnings and contraindications were not available in the compiled data. Please refer to the package insert for the authoritative safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The only clinical evidence is a single-arm-style Phase 2 trial in mixed soft tissue sarcomas, with no liposarcoma-specific results. Reviews indicate that activity in sarcoma is histology-dependent, and other agents (such as trabectedin) are favoured for liposarcoma. The high TxGNN score is not backed by direct clinical evidence. The L2 level reflects the single Phase 2 trial and should not be read as strong evidence for this specific indication.
To proceed, the following is needed:
- Liposarcoma subgroup results from the Phase 2 trials (NCT00217620 and SWOG S0505)
- Detailed mechanism of action data from DrugBank
- Package insert warnings and contraindications from the HSA, to complete safety screening
- Approved indication text for the three Singapore licences
- A comparison against current standard options for liposarcoma and a safety plan for patients with the flagged cardiovascular, haematological and hepatic conditions
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.