Pazopanib
| Evidence Level: L2 | Predicted Indications: 6 |
Table of Contents
Pazopanib: Liposarcoma
One-Sentence Summary
Pazopanib is an oral multi-target tyrosine kinase inhibitor with anti-angiogenic activity, marketed in Australia as Votrient. The TxGNN model predicts it may be useful for liposarcoma. The data compiled for this report include 6 clinical trials (two of them dedicated phase 2 studies in liposarcoma) and 20 publications. Efficacy in the dedicated studies appears modest.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Liposarcoma |
| TxGNN Prediction Score | 0.9959 |
| Evidence Level | L2 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism of action data are not available in the data compiled for this report. The literature describes pazopanib as a multi-target tyrosine kinase inhibitor with anti-angiogenic and antitumorigenic properties. Its action on VEGFR and PDGFR signalling is the basis for its use in sarcoma research.
Liposarcoma is a group of adipocytic soft tissue sarcomas with limited treatment options in the advanced or metastatic setting. Pazopanib has been studied in other soft tissue sarcomas, which gives a biological reason to test it in liposarcoma. Liposarcoma was reportedly excluded from the pivotal pazopanib sarcoma trial because the adipocytic group showed no benefit. Dedicated phase 2 studies (NCT01506596, NCT01692496; PMID 31010343, 28844815) then examined activity in intermediate- and high-grade liposarcoma, with modest results.
Preclinical work also supports some activity. In a patient-derived xenograft model of doxorubicin-resistant pleomorphic liposarcoma with PDGFRA amplification, pazopanib caused tumour regression (PMID 30060824).
Overall, the mechanism is plausible but clinical efficacy is limited. Any use should be restricted to defined settings with careful patient selection.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT01506596 | Phase 2 | Completed | 42 | Single-agent pazopanib in unresectable or metastatic liposarcoma; evaluates effectiveness and safety (direct evidence) |
| NCT01692496 | Phase 2 | Completed | 52 | Pazopanib activity and tolerability in advanced or metastatic liposarcoma that relapsed after standard therapy or has no standard option |
| NCT02357810 | Phase 2 | Completed | 178 | Pazopanib plus oral topotecan in metastatic, non-resectable soft tissue and bone sarcomas (mixed population) |
| NCT01532687 | Phase 2 | Completed | 54 | Randomised, double-blind trial of gemcitabine with or without pazopanib in refractory soft tissue sarcoma (mixed population) |
| NCT02180867 | Phase 2/3 | Completed | 140 | Preoperative radiation (with or without chemotherapy) with or without pazopanib in non-rhabdomyosarcoma soft tissue sarcoma (indirect relevance) |
| NCT06239272 | Phase 1/2 | Recruiting | 139 | Risk-adapted study with maintenance pazopanib, radiation therapy and selinexor in non-rhabdomyosarcoma soft tissue sarcoma (limited relevance) |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31010343 | 2019 | Phase 2 trial report | Expert Opin Investig Drugs | Pazopanib in advanced intermediate- or high-grade liposarcoma, a subtype with few effective treatments |
| 28844815 | 2017 | Commentary | Lancet Oncol | Commentary on pazopanib for advanced liposarcoma |
| 35609512 | 2022 | Review | Oncol Res Treat | Established and experimental systemic options for advanced liposarcoma by subtype |
| 32026050 | 2020 | Review | Curr Treat Options Oncol | Systemic therapy options for dedifferentiated liposarcoma |
| 37298520 | 2023 | Review | Int J Mol Sci | Treatment of dedifferentiated liposarcoma in the era of immunotherapy |
| 28547734 | 2017 | Review | Adv Ther | Proposals for optimal use of pazopanib, trabectedin and eribulin in soft tissue sarcoma |
| 36890471 | 2023 | Trial protocol | BMC Cancer | JCOG1802 randomised phase 2 comparing trabectedin, eribulin and pazopanib as second-line therapy for advanced soft tissue sarcoma |
| 30060824 | 2018 | Preclinical | Tissue Cell | Pazopanib regressed a doxorubicin-resistant, PDGFRA-amplified pleomorphic liposarcoma in a patient-derived mouse model |
| 34356494 | 2021 | Biomarker study | Biology | Molecular profiling of high-risk soft tissue sarcoma before and after neoadjuvant pazopanib |
| 22987955 | 2012 | Review | Ann Oncol | Histology-driven therapy for soft tissue sarcomas, including agents active in liposarcoma |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| Licence 10041L | Votrient | Tablet 400 mg (as hydrochloride) | Not available in the data compiled for this report |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (multi-target tyrosine kinase inhibitor) |
| Myelosuppression Risk | Please refer to the Product Information (PI) warnings and precautions |
| Emetogenicity Classification | Please refer to the Product Information (PI) warnings and precautions |
| Monitoring Items | Full blood count, liver and renal function, blood pressure, ECG/QT, thyroid function and urinary protein, based on the cautions listed below; confirm against the PI |
| Handling Protection | Please refer to the PI and local cytotoxic or hazardous drug handling policy |
Safety Considerations
Label-based warnings and contraindications are not available in the data compiled for this report. Please refer to the TGA-approved Product Information (PI) for these.
Conditions flagged for caution in the reference data (not label text; verify against the PI): hypertension, long QT syndrome and torsades de pointes, liver failure, drug-induced liver injury, hyperbilirubinaemia (including Gilbert syndrome), hypothyroidism, myocardial infarction, intracerebral haemorrhage, active peptic ulcer disease, pancreatitis, proteinuria, diarrhoeal disease, and electrolyte disorders (potassium, calcium, phosphorus).
Drug interactions (100 interactions recorded; the first 20 returned are summarised):
- Major: famotidine, ranitidine, cimetidine, omeprazole, esomeprazole, rabeprazole, dexlansoprazole, clarithromycin, dolasetron. Acid-suppressing agents (H2 blockers and proton pump inhibitors) feature prominently.
- Moderate: pioglitazone, saxagliptin, loperamide, aprepitant, dexamethasone, budesonide (including nasal), bisacodyl, magnesium oxide, polyethylene glycol with electrolytes, eliglustat.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: The evidence level is L2. Two completed phase 2 trials of pazopanib in advanced liposarcoma (NCT01506596, NCT01692496) and a related phase 2 report (PMID 31010343) exist, but there is no phase 3 trial. Reported efficacy is modest, so use should be limited to carefully selected patients in defined settings.
To proceed, the following is needed:
- The full results of NCT01506596 and NCT01692496, including response rate, progression-free survival and a breakdown by liposarcoma subtype
- Detailed mechanism of action data
- TGA Product Information safety content (warnings, contraindications), which is currently unavailable
- A monitoring plan for liver function, blood pressure, QT interval and other cautions, plus an interaction review for acid-suppressing agents
- A comparison with current standard second-line options and a defined patient-selection approach
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.