Lenvatinib
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Lenvatinib: From Thyroid Cancer to Liposarcoma
One-Sentence Summary
Lenvatinib is a multi-target tyrosine kinase inhibitor internationally approved for angiogenesis-driven cancers such as differentiated thyroid cancer, hepatocellular carcinoma, and renal cell carcinoma. The TxGNN model predicts it may also be effective for liposarcoma, supported by 1 completed clinical trial and 4 publications, though the evidence base remains early-stage and the drug is not currently registered in Australia.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not specified in this evidence pack (data gap); internationally, lenvatinib is approved for differentiated thyroid cancer, hepatocellular carcinoma, and renal cell carcinoma |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 99.51% |
| Evidence Level | L3 (completed non-randomised Phase Ib/II trial + supporting literature) |
| Australia Market Status | Not marketed |
| Number of ARTG Entries | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed, evidence-pack-sourced mechanism of action data is not available (flagged as a High-severity data gap; source: DrugBank). Based on widely known pharmacology, lenvatinib is an oral multi-kinase inhibitor targeting VEGFR1‑3, FGFR1‑4, PDGFRα, KIT and RET, and its established anticancer effect works primarily through anti-angiogenesis and inhibition of tumour vasculature.
Lenvatinib’s proven indications (thyroid, hepatocellular, renal cell carcinomas) are all solid tumours with strong angiogenic dependence. Liposarcoma — particularly dedifferentiated and myxoid subtypes — also shows vascular-driven growth, which provides a mechanistic rationale for anti-angiogenic TKIs. This is reinforced clinically: the LEADER study (NCT03526679) combined lenvatinib with eribulin (a mitotic-inhibitor chemotherapy already used in liposarcoma) and reported activity in advanced adipocytic sarcoma and leiomyosarcoma, supporting the plausibility of the TxGNN prediction.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT03526679 | Phase 1/2 | Completed | 30 | Single-arm LEADER study of lenvatinib (anti-angiogenic) plus eribulin (mitotic chemotherapy) in inoperable/metastatic adipocytic sarcoma and leiomyosarcoma |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36129471 | 2022 | Phase Ib/II single-arm trial report | Clinical Cancer Research | LEADER study (NCT03526679) results on safety and efficacy of lenvatinib plus eribulin in advanced liposarcoma and leiomyosarcoma |
| 39103896 | 2024 | Translational/biomarker study | Experimental Hematology & Oncology | CDK4 as a prognostic biomarker in soft tissue sarcoma, with synergistic effect of CDK4 inhibition in sequential treatment of dedifferentiated liposarcoma |
| 29848686 | 2018 | Preclinical study | Anticancer Research | Broad-spectrum preclinical antitumour activity of eribulin combined with mechanistically differing anticancer agents, including liposarcoma models |
| 34326745 | 2021 | Case report | Case Reports in Oncology | Marked tumour size reduction in a dedifferentiated liposarcoma patient with lung/abdominal metastasis using individualised targeted therapy, surgery and chemotherapy |
Australia Market Information
Lenvatinib currently has no ARTG entries and is not marketed in Australia (0 licences recorded).
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-target tyrosine kinase inhibitor / anti-angiogenic agent) |
| Myelosuppression Risk | Low to moderate — TKIs generally cause less myelosuppression than conventional cytotoxics; risk increases when combined with a cytotoxic partner such as eribulin |
| Emetogenicity Classification | Low to moderate |
| Monitoring Items | Blood pressure (hypertension is a known class effect), FBC, liver function, renal function/proteinuria, thyroid function, ECG/QT interval |
| Handling Protection | Oral hazardous/targeted agent — standard oral oncology handling precautions apply (avoid crushing/splitting, use gloves when handling) |
Note: this profile reflects internationally known TKI-class characteristics; formal DrugBank/TGA toxicity data was not retrieved for this evidence pack.
Safety Considerations
Please refer to the TGA-approved Product Information (PI) for safety information — key warnings, contraindications and drug interaction data were not available in this evidence pack (a Blocking-severity data gap for TFDA warning/contraindication data was flagged, preventing initial safety screening).
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanistic rationale is plausible and one completed small (N=30) single-arm Phase Ib/II trial plus supporting literature show early activity in liposarcoma, but the evidence is not yet controlled/randomised, lenvatinib has no current Australian market presence (0 ARTG entries), and a Blocking-severity safety data gap prevents an initial safety assessment.
To proceed, the following is needed:
- TGA/PI-sourced warnings, contraindications and drug interaction data (currently blocking)
- Confirmed mechanism of action documentation from DrugBank
- Larger controlled trial data (current evidence is single-arm, N=30)
- Clarification of Australian regulatory pathway, given the drug is not currently registered
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.