Everolimus
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Everolimus: From an Unrecorded Original Indication to Liposarcoma
One-Sentence Summary
Everolimus (DrugBank DB01590) is identified in supporting literature as an mTOR inhibitor; its original approved indication is not recorded in this evidence pack, and the drug currently holds no marketing authorization on file. The TxGNN model predicts potential efficacy in Liposarcoma, with 1 active clinical trial and 4 supporting publications currently identified for this indication.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not on file — no marketing authorization/license record available in this evidence pack |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 99.88% |
| Evidence Level | L2 |
| EU Market Status | Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed drug-level mechanism-of-action data is not available for Everolimus in this evidence pack. However, the supporting literature (PMID 37967116) explicitly identifies Everolimus as “the mTOR inhibitor everolimus,” used in combination with the CDK4 inhibitor ribociclib, and reports that the two agents “have shown synergistic growth inhibition in multiple tumor models.”
For the predicted indication, dedifferentiated liposarcoma (DDL) has documented activation of the Akt-mTOR and MAPK signaling pathways (PMID 26518767), providing a direct mechanistic rationale for mTOR-pathway inhibition in this tumor type. This is corroborated by an ongoing Phase 2 trial (NCT03114527) combining ribociclib and everolimus specifically in advanced DDL and leiomyosarcoma patients, and by preclinical work on CDK-inhibitor combination strategies in sarcoma models (PMID 36003796).
Because no original indication is on file for this drug, the rationale here rests solely on this pathway-level and combination-trial evidence rather than on cross-indication similarity to an approved use.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03114527 | Phase 2 | Active, not recruiting | 48 | Two-arm study of ribociclib + everolimus in advanced dedifferentiated liposarcoma (Arm A) and leiomyosarcoma (Arm B) patients with ≥1 prior systemic therapy; evaluates anti-tumor activity of the doublet |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37967116 | 2024 | RCT/Phase 2 | Clinical Cancer Research | Reports the ribociclib + everolimus Phase 2 trial (SAR-096); notes CDK4 (ribociclib) and mTOR (everolimus) inhibition show synergistic growth inhibition in tumor models, motivating the combination in DDL/LMS |
| 26518767 | 2016 | Mechanistic | Tumour Biology | Immunohistochemical/in vitro analysis of 99 DDLS specimens showing activation of Akt/mTOR and MAPK pathways, with antitumor effects observed from an mTOR inhibitor in vitro |
| 36003796 | 2022 | Review/Preclinical | Frontiers in Oncology | PDOX mouse model review identifying effective combination therapies with the CDK inhibitor palbociclib for sarcomas, supporting CDK/mTOR combination strategies |
| 29848686 | 2018 | Preclinical | Anticancer Research | Broad-spectrum preclinical activity of eribulin (used for liposarcoma) combined with mechanistically different anticancer agents |
EU Market Information
No marketing authorizations for Everolimus are currently on file (market status: Not Marketed, 0 authorizations recorded).
Cytotoxicity
Included because all predicted indications for this candidate are malignancies (liposarcoma, rhabdomyosarcoma, renal cell carcinoma, dermatofibrosarcoma protuberans) and supporting literature identifies Everolimus as an mTOR inhibitor used in oncology combination regimens.
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (mTOR inhibitor) |
| Myelosuppression Risk | Please refer to the SmPC warnings and precautions |
| Emetogenicity Classification | Please refer to the SmPC warnings and precautions |
| Monitoring Items | Please refer to the SmPC warnings and precautions |
| Handling Protection | Please refer to the SmPC warnings and precautions |
Safety Considerations
Please refer to the SmPC for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The liposarcoma prediction has biologically plausible pathway support (Akt-mTOR/MAPK activation) and an active Phase 2 combination trial (evidence level L2), but a blocking data gap on TFDA label warnings/contraindications prevents completion of the S1 safety screen, and Everolimus has no marketing authorization on file in this jurisdiction.
To proceed, the following is needed:
- TFDA (or equivalent) product label — warnings, precautions, and contraindications (blocking gap DG001)
- Confirmed mechanism of action and DrugBank pharmacological categories (gap DG002)
- Maturation of NCT03114527 (Phase 2, active, expected completion 2025-12) to assess everolimus’s contribution within the combination regimen
- Direct drug-drug interaction (DDI) data — current query returned no results
- Confirmation of marketing/regulatory status in the target jurisdiction
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.