Eribulin

Evidence Level: L5

Predicted Indications: 9

Eribulin

Pharmacist Assessment Report

Eribulin: From Liposarcoma to Autosomal Recessive Familial Mediterranean Fever

One-Sentence Summary

Eribulin is a microtubule dynamics inhibitor, originally used to treat advanced liposarcoma. The TxGNN model’s top-ranked prediction is autosomal recessive familial Mediterranean fever, but this has no clinical trials and no publications supporting it, so it rests on the model score alone. The best-supported prediction in the data compiled for this report is fibroblastic neoplasm (rank 8), with 1 completed Phase 2 trial and 8 publications (mostly preclinical or review).

Quick Overview

Item	Content
Original Indication	Liposarcoma (from the knowledge graph; no approved indication text is recorded in the ARTG data)
Predicted New Indication	Autosomal recessive familial Mediterranean fever (rank 1)
TxGNN Prediction Score	0.9982
Evidence Level	L5
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	Hold

Note: The rank 1 prediction has no supporting studies. Among the ten predictions, fibroblastic neoplasm (score 0.9936) has the strongest evidence (L2, a completed Phase 2 trial) and is the most useful direction to pursue. It is summarised in the sections below.

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, eribulin is a microtubule dynamics inhibitor and a cytotoxic oncology drug. Its efficacy in liposarcoma is established, and mechanistically it may be applicable to other soft tissue sarcomas.

Familial Mediterranean fever (FMF, rank 1). No mechanistic link is supported by the data. FMF is an autoinflammatory disease driven by pyrin inflammasome dysregulation. Colchicine, another microtubule-targeting agent, is standard FMF therapy, which gives only a loose class-level rationale. Eribulin’s cytotoxic toxicity profile is very different, so the high score (0.9982) should be treated as a computational signal only.

Other predictions:

Fibroblastic neoplasm (rank 8): Soft tissue sarcomas are biologically adjacent to liposarcoma. A completed Phase 2 trial in solitary fibrous tumour and preclinical fibrosarcoma data provide supportive context.
Dermatofibrosarcoma protuberans (rank 2): Plausible as a soft tissue sarcoma, but it is driven by the COL1A1-PDGFB fusion and is usually managed with surgery and imatinib. The only literature is a general review.
Ovarian myxoid liposarcoma (rank 5): A liposarcoma subtype, so extrapolation from the approved indication is reasonable, but there is no site-specific evidence.
Mesotheliomas (pleural, peritoneal, biphasic, epithelioid) and cardiac fibrosarcoma: Plausible antimitotic rationale, but prediction only.
Pleural adenomatoid tumour (rank 6): Generally a benign tumour treated surgically, and likely a spurious association.

Clinical Trial Evidence

No trials are registered for the rank 1 indication (familial Mediterranean fever). The only trial in the top ten predictions is for fibroblastic neoplasm (rank 8):

Trial Number	Phase	Status	Enrolment	Key Findings
NCT03840772	Phase 2	Completed	16	ERASING study: eribulin in advanced solitary fibrous tumour (Italian Sarcoma Group). No outcome data were available, so efficacy is unknown.

Literature Evidence

No literature is available for the rank 1 indication. The following publications relate to fibroblastic neoplasm (rank 8). Soft tissue sarcoma chemotherapy review (PMID 27434055) relates to dermatofibrosarcoma protuberans (rank 2) and is listed last.

PMID	Year	Type	Journal	Key Findings
38136399	2023	Review	Cancers	Diagnosis and treatment of extrameningeal solitary fibrous tumours, a rare mesenchymal neoplasm.
28284173	2017	Preclinical (xenograft)	Eur J Cancer	Patient-derived solitary fibrous tumour xenografts showed high sensitivity to doxorubicin/dacarbazine and suggested potential effectiveness of trabectedin or eribulin.
38423656	2024	Preclinical (in vitro)	Anticancer Res	Recombinant methioninase and eribulin showed synergy against fibrosarcoma cells but not normal fibroblasts.
39197933	2024	Preclinical (in vitro)	Anticancer Res	Recombinant methioninase increased eribulin efficacy 16-fold in highly eribulin-resistant fibrosarcoma cells.
40295012	2025	Preclinical (in vitro/in vivo)	In Vivo	Eribulin-resistant fibrosarcoma cells became more malignant but were arrested by combining eribulin with methionine restriction in nude mice.
35906852	2023	Case report	Genes Chromosomes Cancer	Response to entrectinib in an NTRK3-fusion peripheral nerve sheath tumour; limited relevance to eribulin.
39625530	2024	Preclinical (cell line)	Human Cell	Establishment of a myxofibrosarcoma cell line; no direct eribulin evidence.
34383271	2021	Preclinical (cell line)	Human Cell	Establishment of another myxofibrosarcoma cell line; no direct eribulin evidence.
27434055	2016	Review	Cancer	General review of soft tissue sarcoma chemotherapy (dermatofibrosarcoma protuberans, rank 2); indirect support only.

Australia Market Information

ARTG Number	Product Name	Dosage Form	Approved Indication
ARTG 10140Q	Halaven	Solution for I.V. injection containing eribulin mesilate 1 mg in 2 mL	Not recorded in the data compiled for this report

Cytotoxicity

Item	Content
Cytotoxicity Classification	Conventional cytotoxic (microtubule dynamics inhibitor)
Myelosuppression Risk	Please refer to the Product Information (PI) warnings and precautions. The knowledge graph lists neutropenia, agranulocytosis and thrombocytopenia as contraindication-related conditions.
Emetogenicity Classification	Please refer to the Product Information (PI) warnings and precautions
Monitoring Items	Full blood count (with differential), electrolytes (including potassium), ECG for QT prolongation, and neurological assessment for peripheral neuropathy
Handling Protection	Follow cytotoxic drug handling requirements

Safety Considerations

Disease-level contraindication signals (knowledge graph, not label text): long QT syndrome (including familial), thrombocytopenia, potassium deficiency, neutropenia, agranulocytosis, peripheral nervous system disease, peripheral neuropathy and constipation disorder.
Drug Interactions: 100 interactions were identified. Examples shown include:
- Major: dolasetron and cisapride (consistent with QT-prolongation concerns).
- Moderate: clarithromycin, levofloxacin, ondansetron, palonosetron, metronidazole, tinidazole, famotidine, loperamide, simvastatin, rosuvastatin, and several laxatives and bowel-preparation products (bisacodyl, lactulose, lactitol, polyethylene glycol, sodium sulfate, picosulfuric acid, castor oil).

Please refer to the TGA-approved Product Information (PI) for full warnings and contraindications.

Conclusion and Next Steps

Decision: Hold

Rationale: The top-ranked prediction (familial Mediterranean fever) has no trials or literature, and its mechanistic rationale is weak, so it cannot be supported beyond the model score. The strongest signal is fibroblastic neoplasm (completed Phase 2 trial in solitary fibrous tumour, n=16, no results available), which warrants further investigation as a research question rather than a treatment recommendation.

To proceed, the following is needed:

Published results from the ERASING trial (NCT03840772), including response rate and survival outcomes
Mechanism of action data (MOA) from DrugBank
TGA Product Information with approved indication, warnings and contraindications, which is currently missing
Disease-specific evidence for any other predicted indication before it is considered
A safety plan covering QT prolongation, myelosuppression, peripheral neuropathy and the interactions listed above
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.