Lenvatinib
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Lenvatinib: From Original Indication (Data Not Available) to Liposarcoma
One-Sentence Summary
Lenvatinib’s original approved indication is not documented in this evidence pack (the DrugBank/mechanism-of-action record is incomplete), though it is known to be a multi-target tyrosine kinase inhibitor (TKI) used in oncology. The TxGNN model predicts it may be effective for Liposarcoma, with 1 clinical trial and 4 publications currently supporting this direction. The drug is not currently marketed in Denmark.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available in this evidence pack (DrugBank MOA and indication fields are data gaps) |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 99.51% |
| Evidence Level | L2 |
| Denmark Market Status | Not marketed |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in DrugBank for this record. Based on the repurposing rationale supplied with the prediction, Lenvatinib is a multi-targeted tyrosine kinase inhibitor (TKI) acting on VEGFR1-3, FGFR1-4, PDGFRα, KIT and RET — a mechanism class typically applied to angiogenesis-dependent solid tumours.
Liposarcoma is a soft-tissue sarcoma with high dependence on tumour angiogenesis for growth. When combined with eribulin (a microtubule/mitotic inhibitor), lenvatinib’s anti-angiogenic activity may produce a synergistic anti-tumour effect — anti-vascular action alongside direct cytotoxic mitotic disruption.
This combination has already been tested directly in the LEADER study (NCT03526679), a completed Phase Ib/II trial in advanced adipocytic sarcoma and leiomyosarcoma (n=30), providing direct clinical evidence rather than mechanism-only extrapolation. Supporting biomarker research on CDK4 in dedifferentiated liposarcoma further strengthens the molecular rationale for combination treatment in this population.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03526679 | Phase 1/2 | Completed | 30 | Lenvatinib + eribulin in inoperable/metastatic adipocytic sarcoma and leiomyosarcoma; tests combined anti-angiogenic (lenvatinib) and mitotic-targeting (eribulin) activity |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36129471 | 2022 | Phase Ib/II Trial | Clinical Cancer Research | LEADER study (NCT03526679): safety and efficacy of lenvatinib plus eribulin in advanced liposarcoma and leiomyosarcoma |
| 39103896 | 2024 | Preclinical/Biomarker | Experimental Hematology & Oncology | CDK4 as a prognostic biomarker in soft tissue sarcoma; supports rationale for sequential/combination treatment in dedifferentiated liposarcoma |
| 29848686 | 2018 | Preclinical | Anticancer Research | Eribulin combined with mechanistically distinct anticancer agents shows broad-spectrum preclinical antitumour activity |
| 34326745 | 2021 | Case Report | Case Reports in Oncology | Individualized targeted therapy + surgery + chemotherapy achieved tumour size reduction in dedifferentiated liposarcoma with lung metastasis |
Denmark Market Information
Lenvatinib is currently not marketed in Denmark — there are no national (Laegemiddelstyrelsen) or centralised (EMA) marketing authorisations on file for this record (0 licenses).
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-target tyrosine kinase inhibitor: VEGFR1-3, FGFR1-4, PDGFRα, KIT, RET) |
| Myelosuppression Risk | Please refer to the Summary of Product Characteristics (SmPC) warnings and precautions |
| Emetogenicity Classification | Please refer to the Summary of Product Characteristics (SmPC) warnings and precautions |
| Monitoring Items | Please refer to the Summary of Product Characteristics (SmPC) warnings and precautions |
| Handling Protection | Please refer to the Summary of Product Characteristics (SmPC) warnings and precautions |
Safety Considerations
Please refer to the approved Summary of Product Characteristics (SmPC) for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The strongest evidence — a single completed, small (n=30), single-arm Phase Ib/II trial — supports a credible mechanistic rationale but falls short of registrational-quality evidence for liposarcoma specifically. The drug also currently holds zero marketing authorisations in Denmark, and core MOA/safety data are missing from this evidence pack, making a full risk-benefit assessment premature.
To proceed, the following is needed:
- Lenvatinib SmPC (from the relevant EU/EMA authorisation holder) for mechanism of action, warnings, contraindications, and drug interactions
- Confirmation of Danish/EU marketing authorisation status and access pathway
- Larger controlled trial data (Phase 2/3, ideally randomized) in liposarcoma specifically, beyond the single-arm LEADER study
- DDI and myelosuppression/toxicity profile confirmation from DrugBank or SmPC sources
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.