Everolimus
| Evidence Level: L2 | 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, supported by 1 Phase 2 clinical trial (combination with ribociclib) and 4 publications, only one of which reports clinical results. Evidence is limited for this top-ranked prediction. Among the other predictions, unclassified renal cell carcinoma has the strongest evidence.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 0.9988 |
| Evidence Level | L2 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Hold |
The approved indication text is not recorded in the India licence data compiled for this report. The predictions on this page come from the TxGNN model (deep learning) and may reflect similarities the model learned between related diseases, not biological evidence.
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known information, everolimus is an mTOR inhibitor (it blocks mTORC1). The PI3K/AKT/mTOR pathway drives cell growth and is commonly overactive in renal cell carcinoma, which is why everolimus has proven efficacy there.
Dedifferentiated liposarcoma is characterized by CDK4/MDM2 amplification. Combining everolimus with the CDK4/6 inhibitor ribociclib blocks both the cell cycle and the mTOR growth pathway, which may limit compensatory signaling. The two drugs have shown synergistic growth inhibition in multiple tumor models.
This rationale is plausible but so far rests on a single-arm Phase 2 trial with no randomized comparator. Because everolimus was given with ribociclib, its individual contribution cannot be isolated.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03114527 | Phase 2 | Active, not recruiting | 48 | Ribociclib plus everolimus in advanced dedifferentiated liposarcoma (n of arm A within 48) and leiomyosarcoma; single-arm, two-center study assessing anti-tumor activity after at least one prior systemic therapy |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37967116 | 2024 | Phase 2 trial report | Clin Cancer Res | Results of ribociclib plus everolimus in advanced dedifferentiated liposarcoma and leiomyosarcoma; combination is based on CDK4/6 and mTOR targeting |
| 36003796 | 2022 | Review | Front Oncol | Patient-derived xenograft models of sarcoma used to identify combinations with the CDK inhibitor palbociclib (indirect) |
| 29848686 | 2018 | Preclinical | Anticancer Res | Eribulin combined with other anticancer agents in xenograft models (indirect) |
| 41991999 | 2026 | Preclinical | Oncogene | XPO1 inhibitor KPT-330 in dedifferentiated liposarcoma (indirect, not everolimus) |
Other Predicted Indications
| Rank | Predicted Indication | Score | Evidence Level | Assessment |
|---|---|---|---|---|
| 7 | Rhabdomyosarcoma | 0.9974 | L3 | Phase 1 and Phase 1/2 trials in mixed pediatric solid tumors. Rhabdomyosarcoma-specific efficacy is not established. |
| 3 | Dermatofibrosarcoma protuberans | 0.9982 | L4 | Only indirect imatinib-related literature. |
| 2, 4, 5, 6, 8, 10 | Rare liposarcoma, rhabdomyosarcoma and RCC subtypes | 99.72–0.9984 | L5 | Prediction only, with no trials or publications. |
India Market Information
There are 20 valid single-ingredient registrations, all oral tablets. Approved indication text is not available for any of them. Five main registrations:
| Authorization Number | Product Name | Dosage Form | Manufacturer |
|---|---|---|---|
| 2482 | Afinitor 5mg Tablet | Strip of 10 tablets | Novartis India Ltd |
| 2691 | Afinitor 10mg Tablet | Strip of 10 tablets | Novartis India Ltd |
| 75522 | Everotas 5mg Tablet | Strip of 10 tablets | Intas Pharmaceuticals Ltd |
| 35415 | Certican 0.25mg Tablet | Strip of 10 tablets | Novartis India Ltd |
| 237017 | Volantis 5mg Tablet | Strip of 10 tablets | Dr Reddy’s Laboratories Ltd |
Other marketed brands include Evelimus, Xolimus, Everomus, Rapact, Rolimus, Evermil, Everbliss, Evergraf and Lanolimus. Strengths range from 0.25 mg to 10 mg.
Safety Considerations
Package insert warnings and contraindications were not available in the data compiled for this report. Please refer to the package insert for safety information.
The following information comes from a knowledge graph and drug interaction database, not from label text:
- Conditions flagged as contraindication-related in the knowledge graph: liver failure and liver disease, kidney disease, thrombocytopenia, neutropenia, leukopenia, anemia, hyperglycemia, diabetes mellitus, diabetic ketoacidosis, hyperlipidemia and hypertriglyceridemia, interstitial lung disease, congestive heart failure, stomatitis, hemolytic-uremic syndrome, pericardial effusion, and others. These should be verified against the official label.
- Drug interactions: 383 interactions were recorded. Major-level examples include amphotericin B, aprepitant, dexamethasone and clarithromycin. Moderate-level examples include metformin and other antidiabetic agents (acarbose, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 agonists, glimepiride), cimetidine, eliglustat and eluxadoline.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (mTOR inhibitor), not a conventional cytotoxic |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Complete blood count, liver and renal function, blood glucose and lipids (based on the flagged conditions above) |
| Handling Protection | Please refer to the package insert warnings and precautions |
Conclusion and Next Steps
Decision: Hold
Rationale: For liposarcoma, the only direct evidence is one single-arm Phase 2 trial of everolimus combined with ribociclib, so everolimus’s own contribution is unknown. The licence data also lack package insert safety information. Unclassified renal cell carcinoma, by contrast, has stronger Phase 2 evidence and could be considered Proceed with Guardrails, though everolimus is already approved for RCC.
To proceed, the following is needed:
- Full results of the ribociclib plus everolimus trial (NCT03114527, PMID 37967116), including response rate and progression-free survival in the liposarcoma arm
- Randomized or comparative data separating everolimus’s effect from ribociclib’s
- Mechanism of action data from DrugBank
- Package insert warnings, contraindications and approved indications from the India regulatory source
- A safety monitoring plan covering hematologic, metabolic, hepatic and pulmonary risks, and a drug interaction review for CYP3A4-related agents
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.