Lenvatinib
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Lenvatinib: From Renal Cell Carcinoma and Thyroid Cancer to Liposarcoma
One-Sentence Summary
Lenvatinib is an oral multi-targeted kinase inhibitor, originally used for renal cell carcinoma and thyroid cancer. The TxGNN model predicts it may be effective for liposarcoma. Support is limited: 1 completed early-phase clinical trial (a combination with eribulin) and 4 publications, only one of which reports clinical results in patients.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Renal cell carcinoma and thyroid carcinoma (from the knowledge-graph indication list; the Singapore registration records contain no indication text) |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 99.51% |
| Evidence Level | L2 (upper bound: the only trial is single-arm and non-randomized) |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data for lenvatinib is not available in the data compiled for this report. The following is based on general knowledge of the drug. Lenvatinib blocks several growth-signalling receptors: VEGFR1-3, FGFR1-4, PDGFRα, RET and KIT. By doing so it cuts off the blood supply that tumours need and interferes with their proliferative signalling. This anti-angiogenic action is the basis of its use in renal cell and thyroid cancers.
Liposarcoma is a soft tissue sarcoma that also depends on new blood vessel growth. Lenvatinib has been tested with eribulin, a microtubule-targeting chemotherapy already used in advanced liposarcoma. The two drugs act through different mechanisms, so the combination is plausible. Separately, CDK4 amplification is common in well-differentiated and dedifferentiated liposarcoma, and CDK4 inhibition is being studied as a synergistic approach.
The link is therefore reasonable but indirect. The evidence comes from one small single-arm study of a combination, so it does not show that lenvatinib alone is effective.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03526679 | Phase 1/2 | Completed | 30 | LEADER study: single-arm test of lenvatinib plus eribulin in inoperable or metastatic adipocytic sarcoma and leiomyosarcoma. It assesses safety and efficacy, but has no randomized comparator. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36129471 | 2022 | Phase Ib/II single-arm trial | Clin Cancer Res | Published report of the LEADER study (lenvatinib plus eribulin) in advanced liposarcoma and leiomyosarcoma, where treatment options are limited. |
| 39103896 | 2024 | Preclinical/biomarker study | Exp Hematol Oncol | CDK4 as a prognostic biomarker in soft tissue sarcoma, and synergy of CDK4 inhibition in dedifferentiated liposarcoma. |
| 29848686 | 2018 | Preclinical study | Anticancer Res | Eribulin (already used in liposarcoma) shows broad antitumour activity in combination with agents of differing mechanisms. |
| 34326745 | 2021 | Case report | Case Rep Oncol | A patient with dedifferentiated liposarcoma and lung metastasis had a marked tumour reduction with individualized targeted, surgical and chemotherapy treatment. |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form |
|---|---|---|
| SIN14983P | LENVIMA Hard Capsules 10 mg | Capsule |
| SIN14982P | LENVIMA Hard Capsule 4 mg | Capsule |
Both registrations are valid, single-ingredient oral products. No approved indication text is recorded for them in the data compiled for this report.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-targeted tyrosine kinase inhibitor), not a conventional cytotoxic |
| 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 |
When used with eribulin, a cytotoxic chemotherapy, the combination's toxicity and handling requirements need to be assessed together.
Safety Considerations
- Drug Interactions: 100 interactions were identified, and the first 20 retrieved are summarized here.
- Major: dolasetron and cisapride.
- Moderate: famotidine, loperamide, clarithromycin, levofloxacin, naltrexone, and the antiemetics palonosetron and granisetron. Bowel-preparation and laxative agents are also in this group, including bisacodyl, picosulfuric acid, polyethylene glycol with electrolytes, sodium sulfate, castor oil, glycerin, lactitol, lactulose, magnesium citrate and magnesium hydroxide.
- Minor: metronidazole.
Please refer to the package insert for key warnings and contraindications. These were not available in the data compiled for this report.
Conclusion and Next Steps
Decision: Hold
Rationale: Support for liposarcoma comes from a single small, single-arm Phase 1b/2 study of lenvatinib combined with eribulin (n=30), so the contribution of lenvatinib alone is unclear. The package-insert safety information is also missing, which blocks safety screening. The drug is already marketed in Singapore, so access is not the barrier. The evidence is the barrier.
To proceed, the following is needed:
- Complete results and a detailed efficacy readout (response rate, progression-free survival) from the LEADER study, ideally by liposarcoma subtype.
- Randomized or larger controlled data comparing the combination with standard therapy such as eribulin alone.
- Package insert warnings and contraindications from the Singapore regulator (HSA).
- Detailed mechanism-of-action data for lenvatinib.
- A plan for managing drug interactions and combination toxicity, especially with eribulin.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.