Sorafenib
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Sorafenib: From Hepatocellular Carcinoma to Liposarcoma
One-Sentence Summary
Sorafenib is a multikinase inhibitor whose established indications (per literature within this evidence pack) include hepatocellular carcinoma and renal cell carcinoma. The TxGNN model predicts it may be effective for Liposarcoma, with 2 clinical trials and 8 publications currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Hepatocellular Carcinoma (no taiwan_regulatory.licenses or drug.original_indications entries in this evidence pack; inferred from literature evidence, e.g. PMID 40716153, PMID 31118247) |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 99.82% |
| Evidence Level | L2 |
| US Market Status | 未上市 (Not Marketed) |
| Number of NDAs | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
The drug.original_moa field in this evidence pack is not populated. However, literature captured elsewhere in the pack (e.g. PMID 15466206, Wilhelm et al. 2004) directly characterizes sorafenib (BAY 43-9006) as a bi-aryl urea multikinase inhibitor that suppresses the RAF/MEK/ERK signaling pathway and blocks receptor tyrosine kinases involved in tumor progression and angiogenesis — including VEGFR and PDGFR-β.
Soft tissue sarcomas, including liposarcoma, frequently exhibit PDGFR pathway activation and are angiogenesis-dependent, giving a plausible mechanistic bridge from sorafenib’s known anti-VEGFR/PDGFR activity in hepatocellular and renal cancers to liposarcoma. This is not purely theoretical: the SWOG-directed intergroup trial S0505 (PMID 21751200, a completed Phase 2 RCT) directly tested sorafenib in advanced soft tissue sarcomas, and a dedicated Phase 2 trial (NCT00217620, BAY-9006/sorafenib) enrolled 51 patients with advanced soft tissue sarcomas — a category that includes liposarcoma subtypes.
One caveat: the other clinical trial linked to this prediction (NCT02048371, SARC024) actually tested regorafenib, not sorafenib, and appears to be a data-linkage artifact rather than direct evidence (flagged as Grade C relevance in the pack). The liposarcoma-specific signal therefore rests on broader soft-tissue-sarcoma trial data rather than a liposarcoma-dedicated trial, which is why the evidence level is capped at L2 rather than L1.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00217620 | Phase 2 | Completed | 51 | BAY-9006 (sorafenib) tested in advanced soft tissue sarcomas, a category encompassing liposarcoma; sorafenib may block enzymes needed for cell growth and blood flow to tumors. (Relevance: B — direct but broad histology trial) |
| NCT02048371 | Phase 2 | Completed | 131 | SARC024 studied oral regorafenib (not sorafenib) in selected sarcoma subtypes. Drug mismatch — likely a data-linkage artifact; low direct relevance. (Relevance: C) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 21751200 | 2012 | RCT (Phase 2) | Cancer | SWOG-directed intergroup trial S0505: sorafenib evaluated in advanced soft tissue sarcomas; sorafenib targets RAF, VEGFR1-3, PDGFR-B, FLT3, and c-KIT, pathways relevant to STS. |
| 22987955 | 2012 | Review | Annals of Oncology | Histology-driven therapy for soft tissue sarcomas; notes trabectedin’s high activity in myxoid liposarcoma and discusses targeted agent rationale by subtype. |
| 24712007 | 2014 | Review | Magyar Onkologia | Medical treatment of soft tissue sarcomas by histological subtype, covering targeted therapy options including kinase inhibitors. |
| 36003796 | 2022 | Review | Frontiers in Oncology | Reviews sarcoma patient-derived orthotopic xenograft (PDOX) models identifying effective combination therapies including CDK inhibitors, relevant to targeted therapy rationale in sarcoma. |
| 24554062 | 2014 | Phase 1 | Annals of Surgical Oncology | Neoadjuvant conformal radiotherapy plus sorafenib in locally advanced extremity soft tissue sarcoma, based on preclinical synergy between antiangiogenic therapy and radiotherapy. |
| 18413802 | 2008 | Preclinical | Molecular Cancer Therapeutics | Sorafenib inhibits growth and MAPK signaling in malignant peripheral nerve sheath tumor cells and dedifferentiated liposarcoma cell lines (LS141, DDLS). |
| 23416162 | 2013 | Preclinical (xenograft) | American Journal of Pathology | Dedifferentiated liposarcoma xenograft models reveal PTEN down-regulation as a malignant signature and response to PI3K pathway inhibition — informs combination targeted-therapy rationale. |
| 25075796 | 2014 | Case report | Anti-Cancer Drugs | Case report of response to trabectedin in synovial sarcoma with lung metastases — supportive of targeted/non-cytotoxic agent activity in sarcoma family, though not sorafenib-specific. |
US Market Information
No marketing authorization records are present in this evidence pack for the target market region (taiwan_regulatory.total_licenses = 0, market_status = 未上市 / Not Marketed, licenses = []). Sorafenib is marketed internationally (e.g., as Nexavar) for other indications per the clinical trial literature above, but no local license data is available to summarize here.
Cytotoxicity
This drug is antineoplastic — all predicted new indications are cancers, and cited literature repeatedly characterizes sorafenib as a multikinase inhibitor used in first-line treatment of hepatocellular carcinoma.
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multikinase inhibitor: RAF/MEK/ERK pathway, VEGFR, PDGFR-β) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
Please refer to the package insert for safety information.
(Note: this evidence pack flags TFDA/local package insert warnings and contraindications as a Blocking data gap (DG001) — this must be resolved before any Stage 1 safety review.)
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: A completed Phase 2 RCT (SWOG S0505) and a dedicated Phase 2 trial directly evaluated sorafenib in advanced soft tissue sarcoma populations that include liposarcoma, and the PDGFR-β/VEGFR mechanistic rationale is well supported by preclinical liposarcoma-specific data (PMID 18413802, 23416162). However, no liposarcoma-dedicated Phase 2/3 trial exists, and one linked trial (NCT02048371) is a drug mismatch, so evidence should be treated as guardrailed rather than definitive.
To proceed, the following is needed:
- TFDA/local package insert warnings and contraindications (Blocking gap, DG001)
- Confirmed mechanism of action documentation directly attributed to
drug.original_moa(High priority gap, DG002) - Liposarcoma-subtype-specific trial data (current evidence is largely at the broader soft-tissue-sarcoma level)
- Local market/licensing data, since this drug is currently unlicensed/not marketed in the target jurisdiction
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.