Trabectedin
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
- Trabectedin
- Pharmacist Assessment Report
- Trabectedin: From Ovarian Cancer to Female Breast Carcinoma
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Canada Market Information
- Cytotoxicity
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Trabectedin: From Ovarian Cancer to Female Breast Carcinoma
One-Sentence Summary
Trabectedin is a marine-derived DNA-binding cytotoxic agent, originally used to treat ovarian cancer (and, in many countries, soft tissue sarcoma). The TxGNN model predicts it may be effective for female breast carcinoma, with 1 registered clinical trial (a QT-interval safety study, not an efficacy trial) and 20 publications, including several Phase 2 studies, currently supporting this direction.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Ovarian cancer (the Health Canada licence record contains no indication text) |
| Predicted New Indication | Female breast carcinoma |
| TxGNN Prediction Score | 0.9973 |
| Evidence Level | L5 |
| Canada Market Status | Marketed (marketed DINs: 1 of 1) |
| Number of DINs | 1 (marketed: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the database record compiled for this report. Based on the published literature, trabectedin binds the minor groove of DNA and triggers DNA double-strand breaks that depend on transcription-coupled nucleotide excision repair. It also affects the tumour microenvironment by reducing tumour-associated macrophages.
Ovarian and breast cancers share a biology of DNA-repair deficiency. Tumours with BRCA1/2 deficiency (homologous recombination deficiency) appear especially sensitive to trabectedin. This gives a plausible rationale in a subset of breast cancers, particularly BRCA-deficient and triple-negative disease. Preclinical work also suggests trabectedin may enhance the antitumour effect of IL-12 in triple-negative breast cancer.
This rationale rests on the literature rather than on the supplied database record, so it should be treated as hypothesis-generating.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00786838 | Phase 2 | Completed | 76 | Single-blind, placebo-controlled study of the effect of a single trabectedin dose on the QT interval in patients with advanced solid tumours. It is a safety/pharmacology study, not direct evidence of efficacy in breast cancer. |
No registered trial in the compiled data directly tests efficacy in breast cancer. The Phase 2 breast cancer studies appear only in the literature below.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25239225 | 2014 | Phase 2 RCT | Clin Breast Cancer | Single-agent trabectedin in advanced breast cancer after anthracycline and taxane treatment, comparing two administration regimens for efficacy and safety |
| 24692579 | 2014 | Phase 2 | Ann Oncol | Trabectedin activity in germline BRCA1/2-mutated metastatic breast cancer, based on preclinical sensitivity of homologous recombination-deficient tumours |
| 27266804 | 2016 | Phase 2 | Clin Breast Cancer | Trabectedin 1.3 mg/m² in HR-positive, HER2-negative advanced breast cancer, stratified by XPG mRNA expression |
| 26592307 | 2016 | Review | Expert Opin Investig Drugs | Overview of trabectedin in breast cancer, including its effects on transcription and tumour-associated macrophages |
| 27710871 | 2016 | Review | Cancer Treat Rev | Trabectedin as a chemotherapy option for BRCA-deficient tumours |
| 39777457 | 2025 | Preclinical | Cancer Immunol Res | Trabectedin enhanced the antitumour effects of IL-12 in triple-negative breast cancer models |
| 19114300 | 2009 | Phase 1 | Eur J Cancer | Trabectedin plus doxorubicin in advanced soft tissue sarcoma and breast cancer (38 patients: 29 sarcoma, 9 breast) |
| 24941346 | 2014 | Preclinical | Eur Cytokine Netw | Anti-angiogenic effects of trabectedin on human breast cancer cells |
| 23792433 | 2013 | Preclinical | Toxicol Lett | Trabectedin induced apoptosis in both MCF-7 and MDA-MB-453 breast cancer cells, with differences between the two lines |
| 18410797 | 2008 | Review | Semin Oncol | Emerging agents for anthracycline- and taxane-refractory metastatic breast cancer |
The abstracts available for the Phase 2 studies were truncated and did not include outcome results, so efficacy findings cannot be summarised here.
Canada Market Information
| DIN | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 02351528 | YONDELIS | Not specified | Not specified |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (DNA minor-groove binder; marine-derived alkaloid) |
| Myelosuppression Risk | High. The literature reports grade 3–4 neutropenia in about 50% and thrombocytopenia in about 20% of patients; toxicities are mainly haematological and hepatic. |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | CBC with differential and liver function, based on the reported haematological and hepatic toxicity; a QT-interval study has also been conducted |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Drug Interactions: The interaction screen returned 100 interacting drugs in total (the first 20 were provided). Most are Moderate. One is Major: clarithromycin. Other Moderate interactions include aprepitant, dexamethasone, cimetidine, metronidazole, miconazole, levofloxacin, minocycline, bupropion, naltrexone, simvastatin and rosuvastatin. Many of these are commonly co-prescribed with chemotherapy, so a full interaction review is needed before use.
Warnings and contraindications from the Canadian package insert are not available in the compiled data. Please refer to the package insert for them.
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanistic rationale is plausible, particularly for BRCA-deficient and triple-negative breast cancer, and the TxGNN score is high (0.9973). However, the only registered trial is a QT-safety study. Efficacy support comes from Phase 2 publications whose results are not available in the compiled data. Package insert warnings and contraindications are also missing, so safety screening cannot proceed.
To proceed, the following is needed:
- The Health Canada package insert (warnings, contraindications, approved indications, dosage form)
- Full texts and outcome data of the Phase 2 breast cancer studies (PMIDs 25239225, 24692579, 27266804)
- Detailed mechanism-of-action data from DrugBank
- A biomarker-defined target population (for example BRCA1/2 or XPG status)
- A review of the major and moderate drug interactions, especially clarithromycin
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.