Regorafenib
| Evidence Level: L2 | Predicted Indications: 8 |
Table of Contents
Regorafenib: Liposarcoma
One-Sentence Summary
Regorafenib is an oral multi-kinase inhibitor marketed in Canada as STIVARGA. The TxGNN model predicts it may be effective for liposarcoma, but the direct evidence is mixed: 1 completed phase 2 trial and several publications exist, and the dedicated liposarcoma cohort did not show clear benefit. Evidence level: L2.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 0.9976 |
| Evidence Level | L2 |
| Canada Market Status | Marketed (marketed DINs: 1 of 1) |
| Number of DINs | 1 (marketed: 1) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Regorafenib is a multi-kinase inhibitor that blocks angiogenic receptors (VEGFR1-3, TIE2), stromal receptors (PDGFR, FGFR) and oncogenic kinases (KIT, RET, RAF). These pathways drive tumour blood-vessel growth and proliferative signalling, and they are also relevant in soft tissue sarcomas, including liposarcoma.
The model gives this prediction a very high score (0.9976), and there is a real clinical signal in soft tissue sarcoma. However, the signal is subtype-dependent. In the randomized phase 2 REGOSARC trial, the benefit was seen mainly in non-adipocytic sarcomas and not in liposarcoma. The liposarcoma-specific cohort of SARC024 likewise concluded that the results do not support routine use of regorafenib in this population.
The prediction should therefore be viewed as a hypothesis with a plausible mechanism but weak direct clinical confirmation.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT02048371 | Phase 2 | Completed | 131 | SARC024: oral regorafenib in selected sarcoma subtypes, including liposarcoma; the first systematic evaluation outside GIST |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32701199 | 2020 | RCT | The Oncologist | SARC024 liposarcoma cohort (randomized, placebo-controlled phase 2): results do not support routine use of regorafenib in treatment-refractory liposarcoma |
| 27751846 | 2016 | RCT | The Lancet Oncology | REGOSARC: randomized, double-blind, placebo-controlled phase 2 trial in anthracycline-pretreated advanced soft tissue sarcoma |
| 29902612 | 2018 | RCT | European Journal of Cancer | Updated REGOSARC analysis including cross-over: efficacy in leiomyosarcoma, synovial sarcoma and other non-adipocytic sarcomas, but not in liposarcoma |
| 28295221 | 2017 | RCT (post hoc) | Cancer | Quality-adjusted time without symptoms or toxicity analysis of REGOSARC in non-adipocytic sarcoma |
| 29931504 | 2018 | Review | Targeted Oncology | Overview of regorafenib’s growing role in sarcoma, including liposarcoma |
| 40975452 | 2025 | Review | Critical Reviews in Oncology/Hematology | Maintenance therapy after first-line treatment for advanced soft tissue sarcoma |
| 33290314 | 2021 | Retrospective study | Anti-Cancer Drugs | Anlotinib (a related kinase inhibitor) in well-differentiated/dedifferentiated liposarcoma |
| 25884155 | 2015 | Protocol | BMC Cancer | REGOSARC trial design |
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02403390 | STIVARGA | Not listed | Not listed |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-kinase inhibitor) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Complete blood count, liver function (hepatic toxicity is a recognized class concern), renal function and proteinuria, blood pressure |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: The data compiled for this report list 100 interacting drugs. Examples of major interactions include acetylsalicylic acid, deferasirox, ibritumomab tiuxetan, tositumomab, abciximab, alteplase, antithrombin III and apixaban (mostly antithrombotic or bleeding-risk agents). Moderate interactions include dexamethasone, clarithromycin, naltrexone, rosuvastatin and cobicistat.
- Class-related toxicities reported in the literature for anti-angiogenic kinase inhibitors: hand-foot skin reaction, hepatic toxicity, hypertension and proteinuria.
Please refer to the package insert for full warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Regorafenib has a plausible mechanism and a very high model score, and it has been studied in a randomized placebo-controlled phase 2 trial in liposarcoma (evidence level L2, no phase 3 trial). However, that liposarcoma cohort and the broader REGOSARC trial did not show clear benefit in liposarcoma, so any further work should be limited and carefully designed.
To proceed, the following is needed:
- Review of the SARC024 and REGOSARC subtype data to define whether any liposarcoma subpopulation or combination approach merits testing
- Detailed mechanism of action data and package insert warnings and contraindications
- A safety monitoring plan covering hepatic toxicity, bleeding risk, blood pressure and drug interactions
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.