Everolimus
| Evidence Level: L3 | Predicted Indications: 8 |
Table of Contents
Everolimus: Liposarcoma
One-Sentence Summary
Everolimus is an mTOR inhibitor originally used for renal cell carcinoma, breast cancer, and tuberous sclerosis-related conditions. The TxGNN model predicts it may be effective for liposarcoma, with 1 clinical trial (a Phase 2 combination study) and 4 publications currently supporting this direction. Most of that support is indirect or preclinical.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 0.9988 |
| Evidence Level | L3 |
| Canada Market Status | Marketed (marketed DINs on record: at least 20) |
| Number of DINs | at least 20 |
| Recommended Decision | Hold (research question stage) |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the compiled data. Based on known information, everolimus is an mTOR pathway inhibitor. Its efficacy in renal cell carcinoma is established, and mechanistically it may be applicable to liposarcoma.
Dedifferentiated liposarcoma is characterized by CDK4/MDM2 amplification and frequent activation of the PI3K/AKT/mTOR pathway. Everolimus inhibits mTORC1. Combining it with the CDK4/6 inhibitor ribociclib targets two complementary proliferation pathways, and the two drugs have shown synergistic growth inhibition in multiple tumour models.
The evidence is still early. It is limited to one Phase 2 combination trial and preclinical work, and the trial design cannot isolate the contribution of everolimus alone.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03114527 | Phase 2 | Active, not recruiting | 48 | Ribociclib plus everolimus in advanced dedifferentiated liposarcoma and leiomyosarcoma. Single-arm, two-centre study that assesses anti-tumour activity. Completion is expected in December 2026. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37967116 | 2024 | Phase 2 trial report | Clin Cancer Res | Report of the ribociclib plus everolimus trial in advanced dedifferentiated liposarcoma and leiomyosarcoma. Rationale: CDK4/6 targeting in liposarcoma and mTOR targeting in leiomyosarcoma. |
| 36003796 | 2022 | Review (preclinical) | Front Oncol | Patient-derived orthotopic xenograft models of sarcoma used to identify combination therapies with the CDK inhibitor palbociclib. Not specific to everolimus. |
| 29848686 | 2018 | Preclinical | Anticancer Res | Eribulin combined with mechanistically different anticancer agents. Not specific to everolimus. |
| 41991999 | 2026 | Preclinical | Oncogene | The XPO1 inhibitor selinexor disrupts the transcriptional circuitry of dedifferentiated liposarcoma. Not specific to everolimus. |
Canada Market Information
Everolimus has 20 valid single-ingredient licences in Canada, with no combination or cancelled licences. The records compiled for this report do not include dosage form or approved indication text. Five main authorizations are listed below.
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02339501 | AFINITOR | Not available | Not available |
| 02339528 | AFINITOR | Not available | Not available |
| 02369257 | AFINITOR | Not available | Not available |
| 02425645 | AFINITOR DISPERZ | Not available | Not available |
| 02463237 | TEVA-EVEROLIMUS | Not available | Not available |
Other licences include generics from Sandoz, PMS, NAT, and Reddy.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (mTOR inhibitor); not a conventional cytotoxic agent |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Complete blood count, liver and renal function, blood glucose, and lipids |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Disease associations flagged in the knowledge graph (not from label text): liver failure and liver disease, kidney disease, thrombocytopenia, neutropenia, leukopenia, agranulocytosis, anaemia, hyperglycaemia, diabetes mellitus, diabetic ketoacidosis, hypertriglyceridaemia and hyperlipidaemia, interstitial lung disease, congestive heart failure, stomatitis, pericardial effusion, and haemolytic-uraemic syndrome.
- Drug Interactions: 100 interactions were identified. Those retrieved include:
- Major: amphotericin B (including the lipid complex), aprepitant, dexamethasone, clarithromycin
- Moderate: antidiabetic agents such as metformin, acarbose, alogliptin, canagliflozin, dapagliflozin, empagliflozin, glimepiride, linagliptin, dulaglutide, and albiglutide. Others include cimetidine, eliglustat, and eluxadoline.
- Minor: zinc sulfate
Please refer to the package insert for label warnings and contraindications, which are not available in the compiled data.
Conclusion and Next Steps
Decision: Hold
Rationale:
- Liposarcoma has only one single-arm Phase 2 combination trial, so the effect of everolimus alone cannot be separated from ribociclib, and the supporting literature is largely preclinical or not specific to everolimus. The evidence stage is a research question, not a decision-ready case.
To proceed, the following is needed:
- Results from NCT03114527, which is expected to complete in December 2026, including activity in the dedifferentiated liposarcoma cohort.
- Randomized or single-agent evidence that isolates the contribution of everolimus.
- Mechanism of action data, which are not currently available.
- Health Canada package insert warnings and contraindications, which are needed before safety screening.
- A safety monitoring plan covering myelosuppression, metabolic effects, lung toxicity, and the major drug interactions.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.