Pazopanib
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
Pazopanib: From Renal Cell Carcinoma and Soft Tissue Sarcoma to Liposarcoma
One-Sentence Summary
Pazopanib is a multi-targeted tyrosine kinase inhibitor originally used for advanced renal cell carcinoma and non-adipocytic soft tissue sarcoma. The TxGNN model, screening across ten candidate indications for this drug, flags Liposarcoma as the most evidence-mature repurposing signal, supported by 9 clinical trials — including a dedicated Phase II study enrolling liposarcoma patients specifically. The other nine candidates identified in this evidence pack (including dermatofibrosarcoma protuberans and solitary fibrous tumour) show promising but not yet formally scored evidence, or remain at prediction-only (L5) stage, and are not the focus of this report.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in this evidence pack’s regulatory data (no UK licences on file); globally, pazopanib is approved for advanced renal cell carcinoma and advanced non-adipocytic soft tissue sarcoma following prior chemotherapy |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 99.59% |
| Evidence Level | L2 |
| UK Market Status | Not Marketed (per this evidence pack) |
| Number of Marketing Authorisations | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in this evidence pack (flagged as a High-severity data gap). Based on established pharmacological knowledge, pazopanib is a multi-targeted tyrosine kinase inhibitor acting on VEGFR-1/2/3, PDGFR-α/β and c-KIT, producing combined anti-angiogenic and anti-proliferative effects. This class of activity underpins its established use in vascularised, kinase-driven solid tumours such as renal cell carcinoma and soft tissue sarcoma.
Dedifferentiated and myxoid liposarcoma subtypes frequently show PDGFR-α pathway activation. Pazopanib’s direct PDGFR inhibition, combined with VEGFR-mediated restriction of tumour vascular supply, provides a mechanistically coherent rationale for activity in liposarcoma. Notably, the pivotal Phase 3 PALETTE trial — which established pazopanib’s soft tissue sarcoma licence — specifically excluded adipocytic (liposarcoma) subtypes, meaning this indication represents a genuine evidence gap rather than an on-label extension. Subsequent dedicated Phase II studies (see below) have since attempted to close that gap directly.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT01506596 | Phase 2 | Completed | 42 | Pazopanib monotherapy specifically in unresectable/metastatic liposarcoma — direct disease-drug match, highest relevance grade (A) |
| NCT01692496 | Phase 2 | Completed | 52 | Pazopanib activity and tolerability in advanced/metastatic liposarcoma relapsed after standard therapy |
| NCT02357810 | Phase 2 | Completed | 178 | Pazopanib combined with oral topotecan in metastatic/unresectable soft tissue and bone sarcomas |
| NCT02180867 | Phase 2/3 | Active, not recruiting | 140 | Pazopanib ± chemoradiation in newly diagnosed non-rhabdomyosarcoma soft tissue sarcoma (liposarcoma among included subtypes) |
| NCT06239272 | Phase 1/2 | Recruiting | 139 | Maintenance pazopanib with dose-escalated radiotherapy and selinexor in non-rhabdomyosarcoma STS (paediatric/AYA risk-adapted design) |
| NCT01532687 | Phase 2 | Completed | 54 | Randomised gemcitabine ± pazopanib in refractory soft tissue sarcoma (combination design, not single-agent evidence) |
| NCT01900743 | Phase 2 | Completed | 219 | Regorafenib (not pazopanib) vs placebo in anthracycline-pretreated STS, including a liposarcoma cohort — supportive class evidence only |
| NCT02048371 | Phase 2 | Completed | 131 | SARC024 study of regorafenib (not pazopanib) across selected sarcoma subtypes — supportive class evidence only |
| NCT06263231 | Phase 3 | Active, not recruiting | 333 | Intratumoral INT230-6 vs US standard of care in liposarcoma/UPS/leiomyosarcoma — non-pazopanib comparator trial |
Literature Evidence
Currently no related literature available for the liposarcoma indication in this evidence pack.
UK Market Information
No UK marketing authorisations are recorded for pazopanib in this evidence pack (market status: Not Marketed, 0 licences on file). Readers should independently verify current UK licensing status, as pazopanib is known internationally under the brand name Votrient for renal cell carcinoma and soft tissue sarcoma; this pack does not confirm current MHRA authorisation status.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy — multi-targeted tyrosine kinase inhibitor (VEGFR-1/2/3, PDGFR-α/β, c-KIT) |
| 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 and BNF for safety information. Report suspected adverse reactions via the Yellow Card Scheme.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Liposarcoma is supported by multiple Phase II trials, including a dedicated single-agent study (NCT01506596) enrolling liposarcoma patients directly — but the pivotal PALETTE Phase 3 trial for pazopanib’s soft tissue sarcoma licence explicitly excluded this subtype, so confirmatory Phase III evidence in liposarcoma specifically is still lacking (L2).
To proceed, the following is needed:
- TFDA/MHRA SmPC warnings, contraindications and full prescribing information (currently a Blocking-severity data gap; safety review cannot proceed without it)
- Confirmed mechanism of action data from DrugBank (High-severity data gap)
- Confirmation of current UK marketing authorisation status
- Drug-drug interaction data (currently not found)
- Literature review specific to pazopanib in liposarcoma (currently no records captured)
- Formal scoring of the remaining nine candidate indications in this pack, several of which (e.g. dermatofibrosarcoma protuberans, solitary fibrous tumour) already show notable Phase II trial and case-series support pending evaluation
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.