Regorafenib
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Regorafenib: From Colorectal Cancer/GIST to Liposarcoma
One-Sentence Summary
Regorafenib is an oral multi-kinase inhibitor originally developed for metastatic colorectal cancer, gastrointestinal stromal tumours (GIST), and hepatocellular carcinoma. The TxGNN model predicts it may be effective for Liposarcoma, with 2 clinical trials and 9 publications currently available — but the direct trial evidence for this specific subtype is negative, warranting caution.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Metastatic colorectal cancer, GIST, hepatocellular carcinoma (based on literature evidence; no Taiwan regulatory record exists) |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 99.76% |
| Evidence Level | L2 |
| Taiwan Market Status | ✗ Not Marketed (Not marketed) |
| Number of Registrations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Regorafenib is an oral diphenylurea multi-kinase inhibitor that blocks angiogenic receptor tyrosine kinases (VEGFR1-3, TIE2), stromal kinases (PDGFR-β, FGFR), and oncogenic kinases (KIT, RET, RAF/BRAF). It was the first small-molecule multi-kinase inhibitor to demonstrate a survival benefit in metastatic colorectal cancer refractory to standard therapy, and has since been approved for GIST and hepatocellular carcinoma — all highly vascularised tumour types.
Liposarcoma, like other soft tissue sarcomas, is a heterogeneous but generally angiogenesis-dependent malignancy, providing a plausible mechanistic rationale for regorafenib activity via VEGFR/PDGFR blockade. This mechanistic logic is what drives the TxGNN prediction.
However, this mechanistic plausibility is not confirmed by direct trial results. Two dedicated Phase 2 trials specifically tested this hypothesis in liposarcoma cohorts:
- The REGOSARC trial (NCT01900743) found regorafenib effective in leiomyosarcoma, synovial sarcoma, and other non-adipocytic sarcomas, but explicitly not in liposarcoma (PMID 29902612).
- The SARC024 liposarcoma cohort (NCT02048371) concluded that results “do not support the routine use of regorafenib in this patient population” (PMID 32701199).
This is a case where the TxGNN mechanistic prediction is reasonable in principle but has already been tested and refuted in the specific target population. This distinction should be prominent in any downstream decision-making.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01900743 | Phase 2 | Completed | 219 | REGOSARC trial: randomized, placebo-controlled, multi-cohort study of regorafenib in anthracycline-pretreated metastatic soft tissue sarcoma, including a dedicated liposarcoma (Cohort A) arm |
| NCT02048371 | Phase 2 | Completed | 131 | SARC024 blanket protocol testing regorafenib across specific sarcoma subtypes including a dedicated liposarcoma cohort |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27751846 | 2016 | RCT | Lancet Oncol | REGOSARC: regorafenib improved PFS vs placebo in doxorubicin-pretreated advanced STS, but benefit was driven by non-adipocytic subtypes |
| 32701199 | 2020 | RCT | The Oncologist | SARC024 liposarcoma cohort: results do not support routine use of regorafenib in refractory liposarcoma |
| 29902612 | 2018 | RCT (post-cross-over analysis) | Eur J Cancer | Updated REGOSARC analysis confirming efficacy in non-adipocytic STS but not liposarcoma, including post-cross-over activity data |
| 28295221 | 2017 | Cohort/QoL analysis | Cancer | Q-TWiST analysis of REGOSARC showing quality-adjusted clinical benefit in doxorubicin-refractory non-adipocytic sarcoma |
| 25884155 | 2015 | Trial Protocol | BMC Cancer | REGOSARC study protocol describing rationale for testing regorafenib across sarcoma subtypes |
| 29931504 | 2018 | Review | Targeted Oncology | Review of regorafenib’s expanding role in sarcoma treatment across STS subtypes |
| 33290314 | 2021 | Retrospective study | Anti-Cancer Drugs | Retrospective study of anlotinib in liposarcoma; references regorafenib as an approved TKI for non-adipocytic STS (indirect relevance) |
| 40975452 | 2025 | Review | Crit Rev Oncol Hematol | Review of maintenance therapy strategies after first-line treatment for advanced STS |
| 26266019 | 2015 | Case Report | Rare Tumors | Case report of pazopanib activity in Ewing sarcoma; cites regorafenib/SARC024 rationale (indirect relevance) |
Taiwan Market Information
Regorafenib is not currently marketed in Taiwan — the regulatory dataset shows 0 licenses and no registered products. No TFDA-approved indication text is available for this drug in this dataset.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (oral multi-kinase inhibitor; not a conventional cytotoxic agent) |
| Myelosuppression Risk | Low — regorafenib’s dominant toxicities are dermatologic (hand-foot skin reaction), hepatic, and cardiovascular (hypertension) rather than haematological |
| Emetogenicity Classification | Low |
| Monitoring Items | Liver function tests (hepatotoxicity risk per literature), blood pressure, skin examination for hand-foot skin reaction, CBC, electrolytes |
| Handling Protection | Standard oral oncology drug handling precautions apply; not subject to IV cytotoxic handling regulations |
Safety Considerations
- Drug Interactions: 213 total interactions identified in the DDI database. Major-level interactions are predominantly with anticoagulant/antiplatelet agents (e.g., Apixaban, Alteplase, Abciximab, Antithrombin III human, Acetylsalicylic acid) as well as Deferasirox, Ibritumomab tiuxetan, and Tositumomab — consistent with regorafenib’s known bleeding-risk profile and warranting caution with concurrent anticoagulation.
Detailed package insert warnings, contraindications, and TFDA-specific safety labeling are not currently available in this dataset (see data gap DG001 below).
Conclusion and Next Steps
Decision: Hold
Rationale: The two most relevant dedicated trials (REGOSARC, SARC024) directly tested regorafenib in liposarcoma and found it ineffective in this specific subtype, despite showing benefit in other soft tissue sarcoma subtypes. Combined with a blocking data gap on TFDA safety labeling (DG001) and the drug’s non-marketed status in Taiwan, the evidence does not currently support advancing this specific indication.
To proceed, the following is needed:
- TFDA package insert / warnings and contraindications data (DG001, blocking — required before any S1 safety evaluation)
- Formal DrugBank-sourced mechanism of action data (DG002)
- Consider re-evaluating pipeline priority toward better-supported candidates in this evidence pack, such as clear cell renal carcinoma or renal cell carcinoma (general), both of which have positive single-arm Phase 2 evidence (PMID 22959186) rather than a negative trial signal
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.